Pomalidomide improves the effectiveness of CAR-T treatment in the relapsed and refractory multiple myeloma or B-cell leukemia/lymphoma with extramedullary disease.

Relapsed and refractory multiple myeloma (RRMM) and B-cell leukemia/lymphoma with extramedullary disease (EMD) have poor prognosis and high mortality, lack of effective therapeutic approaches. We reported for the first time that 6 patients with malignant hematological diseases with EMD received chimeric antigen receptor (CAR)-T treatment combined with pomalidomide, and CAR-T cells were treated with pomalidomide in vitro to determine its killing activity and cytokine secretion. Three patients with RRMM were given B cell maturation antigen (BCMA)-CAR-T therapy. All 3 patients with B-cell leukemia/lymphoma received CD19/22-CAR-T sequential infusion. There were no treatment-related deaths. The maximum overall response rate (ORR) was 100%. Median follow-up was 211.5 days (75-407 days). Three patients (50%) experienced cytokine release syndrome, all of which were grade 1, and no neurotoxicity was observed. In vitro experiments showed that the killing activity did not differ significantly between BCMA-CAR-T cells with and without pomalidomide (10, 25, or 50 µg/mL) in 8226/U266 cell cocultures (P > .05). Tumor necrosis factor (TNF)-α and interferon (IFN)-γ secretion was significantly higher from 8226 and Raji cells cocultured with BCMA-CAR-T and cluster of differentiation (CD)19-CAR-T cells (P < .05). Based on the cocultures, adding pomalidomide significantly promoted IFN-γ and TNF-α secretion (P < .05). Based on the above clinical and in vitro studies demonstrating the co-administration of pomalidomide with CAR-T cell treatment demonstrated favorable tolerability and therapeutic effectiveness in RRMM or B-cell leukemia/lymphoma.

Crosstalk suppression of extrinsic Fabry-Perot interferometric sensor array based on five-step phase shift demodulation scheme using multiwavelength averaging.

A five-step phase shift demodulation scheme based on a multiwavelength averaging method is proposed to suppress crosstalk within an extrinsic Fabry-Perot interferometric (EFPI) sensor array. The paper focuses on a two-element sensing system based on the EFPI sensors to investigate the crosstalk in the EFPI sensor array. A detailed theoretical analysis of crosstalk suppression using the proposed demodulation method is presented. Numerical simulations and experiments are put forward to demonstrate the effectiveness of the proposed demodulation scheme in suppressing crosstalk under varying parameters. The results of the multiwavelength demodulation scheme indicate superior crosstalk suppression capability in contrast to the conventional five-step phase shift demodulation scheme based on a single-wavelength demodulation method. Furthermore, the paper reveals the enhanced crosstalk suppression capability of the proposed demodulation scheme when the cavity length difference between elements is not equal to zero. It alleviates the requirement for consistent cavity length among different elements in the sensing array. The proposed demodulation scheme exhibits excellent crosstalk suppression capabilities in optical multiplexing arrays by decreasing the dependency on extinction ratio and could be potentially used in the large-scale optical hydrophone array system.

Sublethal effect of chlorpyrifos on predatory behavior and physiology of Eocanthecona furcellata (Hemiptera: Pentatomidae).

Insecticides have been known to reduce the predation efficacy of natural enemies. However, the mechanism of the sublethal effect of insecticides on the functional response of predators remains unclear. This study investigated the sublethal effects of the broad-spectrum insecticide chlorpyrifos on the predatory bug Eocanthecona furcellata (Wolff), which is a potential biological control agent against pests in integrated pest management (IPM) programs. After exposure to a sublethal concentration of chlorpyrifos, the predation capacity and the maximum predatory number of E. furcellata increased by 11.27 and 15.26%, respectively, with prey handling time decreased by 15.07%, and the searching efficiency increased by 5.88-12.61%. Additionally, the intraspecific interference effect was enhanced. Glutathione S-transferase (GST) activity was significantly decreased after 12- to 60-h treatment. At 12 h after treatment, the expression levels of GST gene (GST3), acetylcholinesterase gene (AChE), and cytochrome P450 monooxygenasegene (cyp6B1) were significantly up-regulated by 1.47-, 1.48-, and 2.05-fold, respectively, while GST gene (GST1) was significantly down-regulated by 16.67-fold. These results indicated that a sublethal chlorpyrifos concentration inhibited the GST activity and stimulated the predatory behavior of E. furcellata. The results will advance our understanding of the toxicological mechanism of predatory stink bug responses to insecticides and predict chlorpyrifos' effects on predators in an IPM program.

Mediating effect of body fat percentage in the association between ambient particulate matter exposure and hypertension: a subset analysis of China hypertension survey.

BACKGROUND: Hypertension caused by air pollution exposure is a growing concern in China. The association between air pollutant exposure and hypertension has been found to be potentiated by obesity, however, little is known about the processes mediating this association. This study investigated the association between fine particulate matter (aerodynamic equivalent diameter ≤ 2.5 microns, PM2.5) exposure and the prevalence of hypertension in a representative population in southern China and tested whether obesity mediated this association. METHODS: A total of 14,308 adults from 48 communities/villages in southern China were selected from January 2015 to December 2015 using a stratified multistage random sampling method. Hourly PM2.5 measurements were collected from the China National Environmental Monitoring Centre. Restricted cubic splines were used to analyze the nonlinear dose-response relationship between PM2.5 exposure and hypertension risk. The mediating effect mechanism of obesity on PM2.5-associated hypertension was tested in a causal inference framework following the approach proposed by Imai and Keele. RESULTS: A total of 20.7% (2966/14,308) of participants in the present study were diagnosed with hypertension. Nonlinear exposure-response analysis revealed that exposure to an annual mean PM2.5 concentration above 41.8 µg/m3 was associated with increased hypertension risk at an incremental gradient. 9.1% of the hypertension burden could be attributed to exposure to elevated annual average concentrations of PM2.5. It is noteworthy that an increased body fat percentage positively mediated 59.3% of the association between PM2.5 exposure and hypertension risk, whereas body mass index mediated 34.3% of this association. CONCLUSIONS: This study suggests that a significant portion of the estimated effect of exposure to PM2.5 on the risk of hypertension appears to be attributed to its effect on alterations in body composition and the development of obesity. These findings could inform intersectoral actions in future studies to protect populations with excessive fine particle exposure from developing hypertension.

Prognostic value of platelet-to-basophil ratio (PBR) in patients with primary glioblastoma.

Inflammation is strongly associated with cancers. Our research explored the prognostic role of hematological inflammatory indicators in patients with glioblastoma (GBM). Hundred patients were incorporated finally, and we determined the best cutoff values of these blood markers through X-tile first to perform further survival tests. The prognostic role of peripheral blood cell count and corresponding ratios were assessed using the Kaplan-Meier curve and Cox models to identify variables with independent prognostic significance. Then, variables with independent predictive values were incorporated in constructing the nomogram model to realize quantitative prediction for survival. Nomograms were evaluated using Harrell concordance index, receiver operating characteristic curves, and decision curve analysis to assess clinical benefit. Multivariate analysis indicated that a higher platelet-to-basophil ratio (PBR) (>4575) (hazard ratio = 1.819, 95% confidence interval: 1.110-2.980, P = .018) was associated with poorer overall survival in GBM patients. Based on the PBR nomogram, the predictive accuracy was moderate (concordance index = 0.844, area under curve = 0.632). The PBR could serve as a prognostic biomarker for overall survival in patients with GBM, and nomogram models incorporating the PBR could facilitate comprehensive preoperative survival assessment.

Addition of gadolinium contrast to three-dimensional SSFP MR sequences improves the visibility of coronary artery anatomy in young children.

Objective: This study aims to compare the value of a gadolinium contrast-enhanced 1.5-T three-dimensional (3D) steady-state free precession (SSFP) sequence with that of a noncontrast 3D SSFP sequence for magnetic resonance coronary angiography in a pediatric population. Materials and methods: Seventy-nine patients from 1 month to 18 years old participated in this study. A 3D SSFP coronary MRA at 1.5-T was applied before and after gadolinium-diethylenetriaminepentaaceticacid (DTPA) injection. The detection rates of coronary arteries and side branches were assessed by McNemar's χ2 test. The image quality, vessel length, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of the coronary arteries were analyzed by the Wilcoxon signed-rank test. The intra- and interobserver agreements were evaluated with a weighted kappa test or an intraclass correlation efficient test. Results: A contrast-enhanced scan detected more coronary arteries than a noncontrast-enhanced scan in patients under 2 years old (P < 0.05). The SSFP sequence with contrast media detected more coronary artery side branches in patients younger than 5 years (P < 0.05). The image quality of all the coronary arteries was better after the injection of gadolinium-DTPA in children younger than 2 years (P < 0.05) but not significantly improved in children older than 2 years (P > 0.05). The contrast-enhanced 3D SSFP protocol detected longer lengths for the left anterior descending coronary artery in children younger than 2 years and the left circumflex coronary artery (LCX) in children younger than 5 years (P < 0.05). SNR and CNR of all the coronary arteries in children younger than 5 years and the LCX and right coronary artery in children older than 5 years enhanced after the injection of gadolinium-DTPA (P < 0.05). The intra- and interobserver agreements were high (0.803-0.998) for image quality, length, SNR, and CNR of the coronary arteries in both pre- and postcontrast groups. Conclusion: The use of gadolinium contrast in combination with the 3D SSFP sequence is necessary for coronary imaging in children under 2 years of age and may be helpful in children between 2 and 5 years. Coronary artery visualization is not significantly improved in children older than 5 years.

Predatory stink bug, Eocanthecona furcellata (Wolff) responses to oral exposure route of λ-cyhalothrin via sex-specific modulation manner.

The toxic effects of insecticides on predatory arthropods have closely related to their exposure routes. However, little is known about the effects of insecticide on reproductive parameters when the route of exposure occurs at a trophic level via prey intake. We therefore conducted current studies assessing whether Eocanthecona furcellata adults would be affected by feeding with λ-cyhalothrin-contaminated prey. Reproductive parameters, i.e. prolonged premating and preoviposition durations, reduced number of egg batches and egg amount, disturbed ovarian development, and suppressed expression of reproductive related genes were observed in E. furcellata females by feeding with treated prey. Moreover, reduced survival rate and altered carbohydrate metabolism parameters were detected in male bugs. Biochemical parameters, including MDA content, the activities of three antioxidant enzymes and three detoxification enzymes exhibited sex-specific responses after oral-exposure to λ-cyhalothrin in E. furcellata. The results indicate that the insecticide affects the fitness and leads to impairing reproductive potential via sex-specific modulation manner in predator insects. Taken together, our results provide a comprehensive assessment about detrimental impacts of λ-cyhalothrin-exposure on predators via prey intake, as well as a solid basis for further research to protect the predators from hazardous impacts of insecticides.

[Clinical Characteristics and Nomogram Model of Nosocomial Infection in Patients with Newly Diagnosed Multiple Myeloma].

OBJECTIVE: To explore the clinical characteristics of nosocomial infection in newly diagnosed multiple myeloma(NDMM) patients, and establish a predictive nomogram model. METHODS: The clinical data of 164 patients with MM who were treated in Shanxi Bethune Hospital from January 2017 to December 2021 were retrospectively analyzed. The clinical characteristics of infection were analyzed. Infections were grouped as microbiologically defined infections and clinically defined infections. Univariate and multivariate regression models were used to analyze the risk factors of infection. A nomogram was established. RESULTS: 164 patients with NDMM were included in this study, and 122 patients (74.4%) were infected. The incidence of clinically defined infection was the highest (89 cases, 73.0%), followed by microbial infection (33 cases, 27.0%). Among 122 cases of infection, 89 cases (73.0%) had CTCAE grade 3 or above. The most common site of infection was lower respiratory in 52 cases (39.4%), upper respiratory tract in 45 cases (34.1%), and urinary system in 13 cases (9.8%). Bacteria(73.1%) were the main pathogens of infection. Univariate analysis showed that ECOG ≥2, ISS stage Ⅲ, C-reactive protein ≥10 mg/L, serum Creatinine ≥177 µmol/L had higher correlation with nosocomial infection in patients with NDMM. Multivariate regression analysis showed that C-reactive protein ≥10 mg/L (P＜0.001), ECOG ≥2 (P=0.011) and ISS stage Ⅲ （P=0.024） were independent risk factors for infection in patients with NDMM. The nomogram model established based on this has good accuracy and discrimination. The C-index of the nomogram was 0.779（95%CI: 0.682-0.875）. Median follow-up time was 17.5 months, the median OS of the two groups was not reached (P=0.285). CONCLUSION: Patients with NDMM are prone to bacterial infection during hospitalization. C-reactive protein ≥10 mg/L, ECOG ≥2 and ISS stage Ⅲ are the risk factors of nosocomial infection in NDMM patients. The nomogram prediction model established based on this has great prediction value.

Poor accuracy of single serological IgM tests in children with suspected acute Mycoplasma pneumoniae infection in Guangzhou, China.

Introduction. Early and accurate diagnosis of Mycoplasma pneumoniae (MP) infection of children with pneumonia is at the core of treatment in clinical practice.Gap Statement. Serological immunoglobulin M (IgM) tests for MP infection of children in south China have been rarely described.Aim. To assess the diagnostic performance and clinical application of serodiagnosis of MP infection in paediatric pneumonia patients.Methodology. Serum samples from 144 children diagnosed with MP pneumonia were subjected to a particle agglutination (PA)-based IgM assay. Meanwhile, we used an established suspension array as the reference standard method for the detection of MP DNA in bronchoalveolar lavage fluid (BALF) from all patients to assess the reliability of serological assays.Results. When running immunological testing in single serum samples, 80.6 %(79/98) of cases were diagnosed with MP infection, whereas only 55 (56.1 %) cases were positive in MP DNA analysis. Furthermore, single serum tests for IgM during acute MP infection resulted in 85.5 % (47/55) sensitivity and 25.6 % (11/43) specificity. Nevertheless, immunological testing and MP DNA analysis yielded the same results when paired sera were available for MP IgM antibody testing.Conclusion. Paired serological IgM assays are necessary for the determination of an acute MP infection, whereas single serological IgM testing is unreliable. Moreover, even a short interval of two MP serological tests works well.

Eastern Cooperative Oncology Group, ß2-microglobulin, hemoglobin, and lactate dehydrogenase can predict early grade ≥ 3 infection in patients with newly diagnosed multiple myeloma: A real-world multicenter study.

Introduction: This research explored the clinical application of grade ≥ 3 infection predictive models for the newly diagnosed multiple myeloma (NDMM) population. Methods: It evaluated 306 patients with NDMM based on three different predictive models. The relationship between the grade ≥ 3 infection rates in NDMM and the scores was analyzed retrospectively. The cumulative incidence of early grade ≥ 3 infection was estimated using the Kaplan-Meier method and log-rank test to assess the statistical significance of the difference. To compare the predictive performance in the prediction of infection, the Receiver Operating Characteristic Curve (ROC) curve was used to show the area under the curve (AUC), and DeLong's test was used to analyze the difference in AUC. Results: The incidence of grade ≥ 3 infection within the first 4 months of NDMM was 40.20%. Concerning the FIRST score (predictors: ECOG, ß2-microglobulin, hemoglobin, and lactate dehydrogenase), GEM-PETHEMA score (predictors: albumin, male sex, ECOG, and non-IgA type MM), and Infection Risk model of Multiple Myeloma (IRMM) score (predictors: ECOG, serum ß2-microglobulin, globulin, and hemoglobin), the probability of early grade ≥ 3 infection in the different groups showed statistically significant differences (low-risk vs. high-risk: 25.81% vs. 50.00%, p < 0.001; low-risk vs. moderate-risk vs. high-risk: 35.93% vs. 41.28% vs. 60.00%, p= 0.045; low-risk vs. moderate-risk vs. high-risk: 20.00% vs. 43.75% vs. 52.04%, p < 0.001). Statistical differences existed in the probability of early grade ≥ 3 infection among the different groups by the FIRST and IRMM scores but no statistical differences in the GEM-PETHEMA score (p < 0.001, p< 0.001, and p = 0.090, respectively). The FIRST score showed good discrimination and simple calculation with highest AUC. Further subgroup analysis showed that the FIRST score could still apply for patients treated with bortezomib-based regimen and frail patients. Discussion: Our findings indicate that the FIRST score (consisting of ECOG, ß2-microglobulin, hemoglobin, and lactate dehydrogenase) is a simple and robust infection stratification tool for patients with NDMM and could be used in routine clinical work.

Functional characterization of chemosensory proteins in response to artificial light treatment in Thalassodes immissaria.

BACKGROUND: Chemosensory proteins (CSPs) play a vital role in the response to environmental stimuli in insects. However, the involvement of insect CSPs in the stress response to night-time environmental changes has not been examined. RESULTS: In the current study, four TiCSP genes were first cloned from Thalassodes immissaria by transcriptome and RACE-PCR techniques. TiCSPs had typical characteristics of insect CSPs, including a highly conserved four-cysteine motif and olfactory-specific protein D (OS-D) or OS-D superfamily domains. TiCSP1-4 were clustered classified within different clades in a phylogenetic analysis and were differentially expressed at all developmental stages. Under night-time artificial light stress, the expression levels of TiCSP1 in males were significantly decreased at 24 h, and those of TiCSP2 were decreased in both adult sexes at 48 h. In a molecular docking analysis, TiCSPs showed relatively higher binding affinities with sex pheromone components than with host plant volatile molecules. CONCLUSION: Taking the reduced expression levels of TiCSPs and binding affinities into account, TiCSP1 and TiCSP2 are involved in the stress response processes of T. immissaria under light treatment. Our study supplies basic data for the evaluation of the effects of light interference control technology - an emerging physical control measure on nontarget pests of lychee orchards. © 2023 Society of Chemical Industry.

Evidence for the Participation of Chemosensory Proteins in Response to Insecticide Challenge in Conopomorpha sinensis.

Chemosensory proteins (CSPs) are a type of efficient transporters that can bind various hydrophobic compounds. Previous research has shown that the expression levels of some insect CSPs were significantly increased after insecticide treatment. However, the role of CSPs in response to insecticide challenge is unclear. Conopomorpha sinensis is the most destructive borer pest of litchi (Litchi chinensis) and longan (Euphoria longan) in the Asia-Pacific region. Here, we studied the expression patterns and potential functions of 12 CSP genes (CsCSPs) from C. sinensis in response to λ-cyhalothrin exposure. The spatiotemporal distribution of CsCSPs suggested that they were predominantly expressed in the female abdomen, female legs, and male legs. The expression levels of CsCSPs were affected in a time-dependent manner after λ-cyhalothrin treatment in both sexes of C. sinensis adults. Compared to the control group, the expression levels of CsCSP1, CsCSP2, CsCSP9, and CsCSP12 in females were significantly increased by 2-4 times, while only one CsCSP, three CsCSPs, and two CsCSPs were significantly upregulated in males at three time points post-treatment. The sex-biased variance of CSP expression may be related to sex-specific detoxification enzymatic activities and survival rates of C. sinensis in response to insecticide challenge. Homology modeling and molecular docking analyses showed that the binding energy value of CsCSP1-12 to λ-cyhalothrin was negative and the binding energy between CsCSP9 and λ-cyhalothrin was the lowest (-11.35 kJ/mol). Combined with expression alterations of CsCSP1-12, the results indicate that CsCSP1, CsCSP2, CsCSP9, and CsCSP12 were involved in binding and ferrying of λ-cyhalothrin in C. sinensis.

Decreased cuticular penetration minimizes the impact of the pyrethroid insecticide λ-cyhalothrin on the insect predator Eocanthecona furcellata.

The use of broad-spectrum pesticides may reduce the biological control efficacy of predatory arthropods. Hence, the risks of pesticides to predators need to be evaluated. Here, we assessed the effects of a broad spectrum pyrethroid λ-cyhalothrin on a polyphagous predatory insect Eocanthecona furcellata via contact exposure route. The recommended application rate of λ-cyhalothrin was lower than the LR50 and HQ (in-field) was equal to 0.57, indicating the risk of λ-cyhalothrin to E. furcellata was low. Dried λ-cyhalothrin residue had no effect on the mortality, body weight, protein content of cuticle, or activities of major detoxification enzymes in E. furcellata. Residual of λ-cyhalothrin was only detected in the cuticle and legs of E. furcellata with a decreasing trend as time went by and no λ-cyhalothrin was detected inside the body. Additionally, a comparative transcriptome analysis was conducted to study global changes in gene expression in E. furcellata at different time points following exposure to λ-cyhalothrin-contaminated environment. A total of 57,839 unigenes with an average length of 1044 bp and an N50 of 1820 bp were obtained. In total, 118 and 109 differentially expressed genes (DEGs) at 12 h, and 60 h were identified between two groups. The DEGs were largely enriched in functional categories related to the structural constituent of cuticle. Accordingly, multiple cuticle protein-coding genes were up-regulated at 12 h after pesticide exposure. The present study stressed the importance of evaluating the compatibility between a specific pesticide (λ-cyhalothrin) and E. furcellata via simulating the releasing predators after insecticide application. The data could help optimize the pesticide use, optimizing the ecological services of E. furcellata as a BCA, and expanding its use into more areas of agriculture.

SGR-YOLO: a method for detecting seed germination rate in wild rice.

Seed germination rate is one of the important indicators in measuring seed quality and seed germination ability, and it is also an important basis for evaluating the growth potential and planting effect of seeds. In order to detect seed germination rates more efficiently and achieve automated detection, this study focuses on wild rice as the research subject. A novel method for detecting wild rice germination rates is introduced, leveraging the SGR-YOLO model through deep learning techniques. The SGR-YOLO model incorporates the convolutional block attention module (efficient channel attention (ECA)) in the Backbone, adopts the structure of bi-directional feature pyramid network (BiFPN) in the Neck part, adopts the generalized intersection over union (GIOU) function as the loss function in the Prediction part, and adopts the GIOU function as the loss function by setting the weighting coefficient to accelerate the detection of the seed germination rate. In the Prediction part, the GIOU function is used as the loss function to accelerate the learning of high-confidence targets by setting the weight coefficients to further improve the detection accuracy of seed germination rate. The results showed that the accuracy of the SGR-YOLO model for wild rice seed germination discrimination was 94% for the hydroponic box and 98.2% for the Petri dish. The errors of germination potential, germination index, and average germination days detected by SGR-YOLO using the manual statistics were 0.4%, 2.2, and 0.9 days, respectively, in the hydroponic box and 0.5%, 0.5, and 0.24 days, respectively, in the Petri dish. The above results showed that the SGR-YOLO model can realize the rapid detection of germination rate, germination potential, germination index, and average germination days of wild rice seeds, which can provide a reference for the rapid detection of crop seed germination rate.

Relationship between bronchopulmonary dysplasia phenotypes with high-resolution computed tomography score in early preterm infants.

Objective: To assess the relationship between high-resolution computed tomography (HRCT) abnormalities and clinical phenotypes of bronchopulmonary dysplasia (BPD). Methods: A retrospective, single-center study was carried out at the Children's Hospital of Fudan University between 2013 and 2020. Preterm infants born at ≤ 32 weeks' gestation who were diagnosed with BPD and had HRCT between 40 and 50 weeks postmenstrual age (PMA)were included in the study. HRCT images from six pulmonary lobes were scored based on seven types of pulmonary lesions from two categories: hyperaeration lesions and parenchymal lesions. The hyperaeration score (HS) included scores of decreased attenuation, mosaic attenuation, and bulla/bleb, while the parenchymal score (PS) included those of linear lesion, consolidation, bronchial wall thickening, and bronchiectasis. All seven scores were summed up to create the total score (TS). One-way ANOVA testing or Kruskal-Wallis testing was adopted for the comparison of HRCT scores with BPD severity and clinical phenotypes. The correlation between HRCT scores and clinical phenotypes was evaluated by Spearman's correlation analysis. Results: A total of 81 cases were included in the study. Cases with more severe BPD had a higher TS (p = 0.01), HS (p = 0.02), PS (p = 0.02), mosaic attenuation score (p = 0.03), bulla/Bleb score (p = 0.03), and linear density score (p = 0.01). TS (r = 0.28), PS (r = 0.35), linear density (r = 0.34), and consolidation (r = 0.24) were correlated with pulmonary hypertension (PH). However, no HRCT score was significantly different between the patients with or without tracheobronchomalacia (TBM). BPD patients with a combination of lung parenchymal disease, PH, and TBM had the highest TS and HS. Conclusion: HRCT scores correlated with BPD severity and PH in our study. HS might be a useful tool in the assessment of BPD severity while linear densities and consolidation might be helpful in predicting PH.

Chronic fluoxetine enhances extinction therapy for PTSD by evaluating brain glucose metabolism in rats: an [18F]FDG PET study.

BACKGROUND: Recent studies suggest that selective serotonin reuptake inhibitors (SSRIs) and exposure therapies have been used to reduced footshock-induced posttraumatic stress disorder (PTSD) symptoms. However, the therapeutic effect of the combination of SSRIs treatment with exposure therapy remains a matter of debate. This study aimed to evaluate these therapeutic effect through the behavioural and the neuroimaging changes by positron emission tomography (PET) in model rats. METHODS: Pavlovian fear conditioning paradigm to establish model rats, and serial PET imaging with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) was performed during the control, fear-conditioning, and extinction-retrieval phases. The expression of c-Fos was used to identify neural activity. RESULTS: We report that fear conditioning increased glucose metabolism in the right amygdala and left primary visual cortex but decreased glucose metabolism in the left primary somatosensory cortex. After extinction retrieval, there was increased [18F]FDG uptake in the left striatum, left cochlear nucleus and right primary visual cortex but decreased uptake in the anterior cingulate cortex in the extinction group. Fluoxetine increased [18F]FDG uptake in the left hippocampus and right primary visual cortex but decreased uptake in the bilateral primary somatosensory cortex, left primary/secondary motor cortex and cuneiform nucleus. The combined therapy increased [18F]FDG uptake in the left hippocampus, left striatum, right insular cortex, left posterior parietal cortex, and right secondary visual cortex but reduced uptake in the cerebellar lobule. c-Fos expression in the hippocampal dentate gyrus and anterior cingulate cortex in the fluoxetine and combined groups was significantly higher than that in the extinction group, with no significant difference between the two groups. CONCLUSIONS: Chronic fluoxetine enhanced the effects of extinction training in a rat model of PTSD. In vivo PET imaging may provide a promising approach for evaluation chronic fluoxetine treatment of PTSD.

Imaging characteristics of pulmonary BCG/TB infection in patients with chronic granulomatous disease.

In China, tuberculosis (TB) is endemic and the Bacillus Callmette-Güerin (BCG) vaccine is administered to all the newborns, which may lead to BCG infection in patients with chronic granulomatous disease (CGD). Infection of BCG/TB in CGD patients can be fatal and pulmonary is the most affected organ. Our objective was to assess the imaging of pulmonary BCG/TB infection in CGD. We screened 169 CGD patients and identified the patients with pulmonary BCG/TB infection. BCG infection was diagnosis according to the vaccination history, local infection manifestation, acid-fast bacilli staining, specific polymerase chain reaction, and/or spoligotyping. PPD, T-SPOT and acid-fast bacilli staining were used for diagnosis of TB. Totally 58 patients were identified, including TB (n = 7), solely BCG (n = 18), BCG + bacterial (n = 20), and BCG + fungi (n = 13). The onset of BCG disease was much earlier than TB. For those patients only with BCG, lymphadenopathy was the first and most prevalent feature. The most found location was the left axilla, followed by the ipsilateral cervical areas and mediastinal or hilar area. On chest CT, ground-glass opacities, multiple nodules and pulmonary scarring were the most common findings. For TB patients, the pulmonary infections were more serious, including large masses, severe lymphadenopathy, and extensive pulmonary fibrosis. Pulmonary infection of BCG were more common than TB in CGD patients, but much less severe.

Distinct lipid membrane-mediated pathways of Tau assembly revealed by single-molecule analysis.

The conversion of intrinsically disordered Tau to highly ordered amyloid aggregates is associated with a wide range of neurodegenerative diseases termed tauopathies. The presence of lipid bilayer membranes is a critical factor that accelerates the abnormal aggregation of Tau protein. However, the lipid membrane-induced conformational changes of Tau and the mechanism for the accelerated fibrillation remain elusive. In this study, single-molecule Förster resonance energy transfer (smFRET) and fluorescence correlation spectroscopy (FCS) were applied to detect the conformational changes and intermolecular interactions of full-length Tau in the presence of different concentrations of 1,2-dimyristoyl-sn-glycero-3-phosphatidylserine (DMPS) vesicles. The results show that the conformation of Tau becomes expanded with opening of the N-terminal and C-terminal domains of Tau upon binding to DMPS. At low DMPS concentrations, Tau forms oligomers with a partially extended conformation which facilitates the amyloid fibrillization process. At high DMPS concentrations, Tau monomer binds to lipid membranes in a fully expanded conformation at low density thus inhibiting intermolecular aggregation. Our study reveals the underlying mechanisms by which lipid membranes influence amyloid formation of Tau, providing a foundation for further understanding of the pathogenesis and physiology of the interplay between Tau protein and lipid membranes.

Evaluation of comprehensive myocardial contractility in children with Kawasaki disease by cardiac magnetic resonance in a large single center.

BACKGROUND: Children with Kawasaki disease (KD) and coronary artery lesions (CALs) can develop myocardial ischemia, fibrosis, and abnormal contractility. We aimed to assess the association between myocardial mechanical deformation with myocardial fibrosis, ischemia, and CALs. METHODS: In total, 76 KD and 20 healthy volunteers received cardiac magnetic resonance (CMR). Peak systolic left ventricular (LV) longitudinal, radial, and circumferential strain and strain rate [LV strain longitudinal (LVSL), LV strain radial (LVSR), LV strain circumferential (LVSC), LV strain rate longitudinal (LVSRL), LV strain rate radial (LVSRR), and LV strain rate circumferential (LVSRC)], along with late gadolinium enhancement (LGE), perfusion deficit, and CALs in related segments were analyzed. The KD group was subdivided by CALs, perfusion, and LGE results, and strain results were compared with controls and in subgroups. RESULTS: Cardiac fibrosis and ischemia were not confined to the territory of CALs. In a global analysis, strain and strain rates were lower in the KD group, especially in the subgroup with LGE and perfusion deficit. In segmental analysis, LVSR, LVSC, LVSL, and LVSRR decreased in the giant aneurysm group, and a lower LVSR (20.369%±10.603% vs. 26.071%±12.349%) and LVSC (-13.37%±5.365% vs. -15.847%±5.778%) were observed in thrombosed segments. The strain and strain rate were all lower in segments with LGE and perfusion deficit, and no obvious difference was found between groups with and without stenosis. LVSR had a better ability to identify giant aneurysm, thrombosis, stenosis, perfusion deficit, and LGE. CONCLUSIONS: We detected lower strain values in KD patients, which was more pronounced in segments with aneurysm, thrombi, LGE, and perfusion deficit. LVSR is useful to discern patients with higher risk.