Coexistence of hereditary spherocytosis with SPTB P.Trp1150 gene variant and Gilbert syndrome: A case report and literature review.

A congenital protein anomaly in the erythrocyte membrane skeleton causes a hereditary haemolytic illness known as hereditary spherocytosis (HS). The primary characteristic of HS is an increase in the number of tiny spherical red blood cells in the peripheral blood. The chief clinical features of HS include anaemia, jaundice, splenomegaly, spherical erythrocytosis in the blood, chronic anaemia with haemolysis, and recurrent acute attacks. Most patients have a family history; some have autosomal recessive inheritance, whereas most have autosomal dominant inheritance. In cases of severe hyperbilirubinemia disproportionate to haemolysis, other causes of hyperbilirubinemia should be considered. Gilbert syndrome (GS) is an autosomal dominant illness caused by the reduced activity of uridine diphosphate-glucuronosyl transferase lAl and is characterised by intermittent hyperbilirubinemia without any other signs or symptoms of liver disease. The possibility of the coexistence of HS and GS is very limited. Here we present the case of an elderly man with yellow skin and sclera recurring anaemia, and a final diagnosis of coexisting HS and GS.

Dose Response to Upper Extremity Stroke Rehabilitation Varies by Individual: Early Indicators of Treatment Response.

BACKGROUND: Dose response has remained a priority area in motor rehabilitation research for decades, prompting several large randomized trials and meta-analyses. These between-subjects comparisons have revealed equivocal relationships between the duration of motor practice and rehabilitation response. Prior reliance on time-consuming clinical assessments made it infeasible to capture within-subjects dose response, as tracking the dose-response trajectory of an individual requires dozens of repeated administrations. METHODS: This secondary observational cohort analysis of existing data from the gaming arms of the VIGoROUS multisite trial (Video Game Rehabilitation for Outpatient Stroke) describes the rehabilitation dose response of 80 participants with mild-moderate chronic stroke. The 3-dimensional joint position data were captured via the Kinect v2 optical sensor as participants completed a prescribed 15 hours of in-home unsupervised game-based motor practice. Kinematic dose response trajectories were fitted from hundreds to thousands of in-game repetitions for 4 separate upper extremity movements for each participant. RESULTS: Of 75 participants with sufficient data for dose-response analysis, 85% showed improved motor capacity for at least 1 movement. Dose response was bimodal; 42% required <5 hours of motor practice before reaching a plateau in movement kinematics, whereas 55% required >10 and 34% required >30 hours. We could predict with 93% accuracy whether or not an individual would ultimately respond to game-based motor practice within 5 hours of gameplay. CONCLUSIONS: Dose response varies considerably between individuals. About half of chronic stroke patients benefit from higher doses of motor practice than the current standard of care. Individualized dose-response data from motion capture rehabilitation gaming can guide clinical decision-making early on in treatment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02631850.

Long-term exposure to the mixture of phthalates induced male reproductive toxicity in rats and the alleviative effects of quercetin.

Phthalates (PEs), such as di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and butyl benzyl phthalate (BBP) could cause reproductive and developmental toxicities, while human beings are increasingly exposed to them at low-doses. Phytochemical quercetin (Que) is a flavonoid that has estrogenic effect, anti-inflammatory and anti-oxidant effects. This study was conducted to assess the alleviative effect of Que. on male reproductive toxicity induced by the mixture of three commonly used PEs (MPEs) at low-dose in rats, and explore the underlying mechanism. Male rats were treated with MPEs (16 mg/kg/day) and/or Que. (50 mg/kg/d) for 91 days. The results showed that MPEs exposure caused male reproductive injuries, such as decreased serum sex hormones levels, abnormal testicular pathological structure, increased abnormal sperm rate and changed expressions of PIWIL1 and PIWIL2. Furthermore, MPEs also changed the expression of steroidogenic proteins in steroid hormone metabolism, including StAR, CYP11A1, CYP17A1, 17ß-HSD, CYP19A1. However, the alterations of these parameters were reversed by Que. MPEs caused male reproductive injuries in rats; Que. inhibited MPEs' male reproductive toxicity, which might relate to the improvement of testosterone biosynthesis.

Subcutaneous fat predicts bone metastasis in breast cancer: A novel multimodality-based deep learning model.

OBJECTIVES: This study explores a deep learning (DL) approach to predicting bone metastases in breast cancer (BC) patients using clinical information, such as the fat index, and features like Computed Tomography (CT) images. METHODS: CT imaging data and clinical information were collected from 431 BC patients who underwent radical surgical resection at Harbin Medical University Cancer Hospital. The area of muscle and adipose tissue was obtained from CT images at the level of the eleventh thoracic vertebra. The corresponding histograms of oriented gradients (HOG) and local binary pattern (LBP) features were extracted from the CT images, and the network features were derived from the LBP and HOG features as well as the CT images through deep learning (DL). The combination of network features with clinical information was utilized to predict bone metastases in BC patients using the Gradient Boosting Decision Tree (GBDT) algorithm. Regularized Cox regression models were employed to identify independent prognostic factors for bone metastasis. RESULTS: The combination of clinical information and network features extracted from LBP features, HOG features, and CT images using a convolutional neural network (CNN) yielded the best performance, achieving an AUC of 0.922 (95% confidence interval [CI]: 0.843-0.964, P< 0.01). Regularized Cox regression results indicated that the subcutaneous fat index was an independent prognostic factor for bone metastasis in breast cancer (BC). CONCLUSION: Subcutaneous fat index could predict bone metastasis in BC patients. Deep learning multimodal algorithm demonstrates superior performance in assessing bone metastases in BC patients.

Pectoralis muscle predicts distant metastases in breast cancer by deep learning radiomics.

BACKGROUND: Sarcopenia is associated with a poor prognosis in patients with breast cancer (BC). Currently, there are few quantitative assessments carried out between muscle biomarkers and distant metastasis using existing methods. PURPOSE: To assess the predictive value of the pectoralis muscle for BC distant metastasis, we developed a deep learning radiomics nomogram model (DLR-N) in this study. MATERIAL AND METHODS: A total of 493 patients with pathologically confirmed BC were registered. Image features were extracted from computed tomography (CT) images for each patient. Univariate and multivariate Cox regression analyses were performed to determine the independent prognostic factors for distant metastasis. The DLR-N was built based on independent prognostic factors and CT images to predict distant metastases. The model was assessed in terms of overall performance, discrimination, calibration, and clinical value. Finally, the predictive performance of the model was validated using the testing cohort. RESULTS: The developed DLR-N combined multiple radiomic features and clinicopathological factors and demonstrated excellent predictive performance. The C-index of the training cohort was 0.983 (95% confidence interval [CI] = 0.969-0.998) and the C-index of the testing cohort was 0.948 (95% CI = 0.917-0.979). Decision curve analysis (DCA) showed that patients could benefit more from incorporating multimodal radiomic features into clinicopathological models. CONCLUSIONS: DLR-N verified that there were biomarkers at the level of the fourth thoracic vertebra (T4) that affected distant metastasis. Multimodal prediction models based on deep learning could be a potential method to aid in the prediction of distant metastases in patients with BC.

IGF2BP2 promotes lncRNA DANCR stability mediated glycolysis and affects the progression of FLT3-ITD + acute myeloid leukemia.

Internal tandem duplication (ITD) is the most common type of FLT3 mutation (FLT3-ITD), accounting for about 25% of AML patients. The expression of DANCR in FLT3-ITD AML had not been paid attention to, and whether its regulatory relationship with IGF2BP2 can affect the progression of FLT3-ITD AML was unclear. Our study sought to verify the biological role of IGF2BP2 as an m6A reading protein in FLT3-ITD AML. To further explore the role and mechanism of DANCR in AML, and provide a basis for the screening of biomarkers and the development of targeted drugs. The results show that IGF2BP2 was upregulated in FLT3-ITD+ AML patients and cells. Si-IGF2BP2 could inhibit the proliferation, glycolytic and promote the apoptosis in MV4-11 cells. IGF2BP2 could promote the DANCR RNA stability. This discovery will provide new horizons for early screening and targeted therapy of FLT3-ITD+ AML.

METTL3 affects FLT3-ITD+ acute myeloid leukemia by mediating autophagy by regulating PSMA3-AS1 stability.

The study was designed to explore the role of PSMA3-AS1 in initiation and progression of acute myeloid leukemia (AML) and investigate its action mechanism. Expression of PSMA3-AS1, miR-20a-5p and ATG16L1 both in vitro and in vivo was measured by qRT-PCR. The expression of protein was detected by western blot assay. Edu staining and flow cytometry were utilized to measure cell proliferation and apoptosis. Potential target was predicted by bioinformatics and was verified by dual-luciferase report gene assay and RNA pull down assay. QRT-PCR was used to quantify autophagy (LC3, Beclin1, P62) related genes. The m6A modification test is used to verify the effect of METTL3 on PSMA3-AS1. Tumor model was used to identify the effect of PSMA3-AS1 on tumor growth in vivo, and immunohistochemistry was applied to detect expression of ki67 and TUNEL. The results indicate that PSMA3-AS1 was upregulated in FLT3-ITD+ AML patients. Si-PSMA3-AS1 could inhibit the proliferation, autophagy and promote the apoptosis in MV4-11 and Molm13 cells. METTL3 could enhance the PSMA3-AS1 RNA stability. In addition, this study revealed that PSMA3-AS1 affected FLT3-ITD+ AML by targeting expression of miR-20a-5p, and miR-20a-5p further modulated expression of ATG16L1, an mRNA that down-regulated in AML, to affect disease advancement. PSMA3-AS1 could promote FLT3-ITD+ AML progression by regulating the level of autophagy through miR-20a-5p/ATG16L1 pathway. In addition, the increase of PSMA3-AS1 may be caused by the involvement of METTL3 in regulating its stability. This discovery will provide new horizons for early screening and targeted therapy of FLT3-ITD+ AML.

The Geometry of Nanoparticle-on-Mirror Plasmonic Nanocavities Impacts Surface-Enhanced Raman Scattering Backgrounds.

Surface-enhanced Raman scattering (SERS) has garnered substantial attention due to its ability to achieve single-molecule sensitivity by utilizing metallic nanostructures to amplify the exceedingly weak Raman scattering process. However, the introduction of metal nanostructures can induce a background continuum which can reduce the ultimate sensitivity of SERS in ways that are not yet well understood. Here, we investigate the impact of laser irradiation on both Raman scattering and backgrounds from self-assembled monolayers within nanoparticle-on-mirror plasmonic nanocavities with variable geometry. We find that laser irradiation can reduce the height of the monolayer by inducing an irreversible change in molecular conformation. The resulting increased plasmon confinement in the nanocavities not only enhances the SERS signal, but also provides momentum conservation in the inelastic light scattering of electrons, contributing to the enhancement of the background continuum. The plasmon confinement can be modified by changing the size and the geometry of nanoparticles, resulting in a nanoparticle geometry-dependent background continuum in SERS. Our work provides new routes for further modifying the geometry of plasmonic nanostructures to improve SERS sensitivity.

The role of atmospheric conditions in the nonradiative recombination in individual CH3NH3PbI3 perovskite crystals.

Organic-inorganic metal halide perovskites have been emerging as potential candidates for lightweight photovoltaic applications in space. However, fundamental physics concerning the effect of atmosphere on the radiative and nonradiative recombination in perovskites remains far from well understood. Here, we investigate the creation and annihilation of nonradiative recombination centers in individual CH3NH3PbI3 perovskite crystals by controlling the atmospheric conditions. We find that the photoluminescence (PL) of individual perovskite crystals can be quenched upon exposure from air to vacuum, while the subsequent PL enhancement in air shows a pressure dependence. Further analysis attributes the PL decline in vacuum to the activation of nonradiative trap sites, which is likely due to the lattice distortion caused by the variation of local strain on perovskites. With a gradual increase of the air pressure, the light-assisted chemisorption of oxygen on perovskite will passivate these nonradiative trap sites while simultaneously restoring the lattice imperfection, leading to PL enhancement. The present findings suggest that placing the perovskite in an environment with moderate oxygen content can protect the material from photophysical losses that can be pronounced under inert conditions.

Hes1 Controls Proliferation and Apoptosis in Chronic Lymphoblastic Leukemia Cells by Modulating PTEN Expression.

Hairy and enhancer of split homolog-1 (HES1), regulated by the Notch, has been reported to play important roles in the immune response and cancers, such as leukemia. In this study, we aim to explore the effect of HES1-mediated Notch1 signaling pathway in chronic lymphocytic leukemia (CLL). Reverse transcription quantitative polymerase chain reaction and Western blot assay were conducted to determine the expression of HES1, Notch1, and PTEN in B lymphocytes of peripheral blood samples of 60 CLL patients. We used lentivirus-mediated overexpression or silencing of HES1 and the Notch1 signaling pathway inhibitor, MW167, to detect the interaction among HES1, Notch1, and PTEN in CLL MEC1 and HG3 cells. MTT assay and flow cytometry were employed for detection of biological behaviors of CLL cells. HES1 and Notch1 showed high expression, but PTEN displayed low expression in B lymphocytes of peripheral blood samples of patients with CLL in association with poor prognosis. HES1 bound to the promoter region of PTEN and reduced PTEN expression. Overexpression of HES1 activated the Notch1 signaling pathway, thus promoting the proliferation of CLL cells, increasing the proportion of cells arrested at the S phase and limiting the apoptosis of CLL cells. Collectively, HES1 can promote activation of the Notch1 signaling pathway to cause PTEN transcription inhibition and the subsequent expression reduction, thereby promoting the proliferation and inhibiting the apoptosis of CLL cells.

Altered cerebellar gray matter and cerebellar-cortex resting-state functional connectivity in patients with bipolar disorder â .

BACKGROUND: Bipolar disorder (BP) is a common psychiatric disorder characterized by extreme fluctuations in mood. Recent studies have indicated the involvement of cerebellum in the pathogenesis of BP. However, no study has focused on the precise role of cerebellum exclusively in patients with bipolar I disorder (BP-I). METHODS: Forty-five patients with BP-I and 40 healthy controls were recruited. All subjects underwent clinical evaluation and Magnetic Resonance diffusion Tension Imaging scans. For structural images, we used a spatially unbiased infratentorial template toolbox to isolate the cerebellum and then preformed voxel-based morphometry (VBM) analyses to assess the difference in cerebellar gray matter volume (GMV) between the two groups. For the functional images, we chose the clusters that survived from VBM analysis as seeds and performed functional connectivity (FC) analysis. Between-group differences were assessed using the independent Students t test or the nonparametric Mann-Whitney U Test. For multiple comparisons, the results were further corrected with Gaussian random field (GRF) approach (voxel-level P < 0.001, cluster-level P < 0.05). RESULTS: Compared with healthy controls, BP-I patients showed significantly decreased GMV in left lobule V and left lobule VI (P < 0.05, GRF corrected). The FC of cerebellum with bilateral superior temporal gyrus, bilateral insula, bilateral rolandic operculum, right putamen, and left precentral gyrus was disrupted in BP-I patients (P < 0.05, GRF corrected). CONCLUSIONS: BP-I patients showed decreased cerebellar GMV and disrupted cerebellar-cortex resting-state FC. This suggests that cerebellar abnormalities may play an important role in the pathogenesis of BP-I.

Effect of EPA on Hsp90 and GRα protein expression in multiple myeloma drug-resistant cells.

BACKGROUND: Approximately 20% of MM patients harbor glucocorticoid (GC) resistance and are not responsive to therapeutic effect. Chaperoneheat-shock proteins Hsp90 is needed for ligand docking, The imbalance of Hsp90/GRα (glucocorticoid receptor α) may be an important cause of GC resistance. Recent studies have indicated that EPA could repress cancer cell growth by regulating critical influential factors in progression of cancer, consisting of resistance to drugs, chemosensitivity. The aim of the present study was to test the cytotoxic effects of EPA alone or EPA + Dexamethasone in dexamethasone-resistant MM cell (MM.1R) and investigate whether DHA can induce apoptosis and reverse acquired glucocorticoid resistance in dexamethasone-resistant MM cell (MM.1R). METHODS: Cell Counting Kit-8 (CCK-8) was used to detect the proliferation of MM.1R cells after treating with EPA alone and EPA combined with DEX. Mitochondrial membrane potential was measured by flow cytometry and GRα and Hsp90 protein expression were assessed by western blot analysis. RESULTS: EPA alone was able to inhibit cell proliferation as evidenced by CCK-8 assay and the tumor growth was remarkably suppressed by EPA + Dexamethasone, Cell apoptosis after EPA treatment was obviously observed by Flow cytometry analysis of the mitochondrial membrane potential. Analysis of Hsp90 and GRα proteins in MM.1R cells incubated with EPA revealed down-regulation of Hsp90 and up-regulation of GRα. Accordingly, the Hsp90/GRα ratio was significantly decreased with the increase of EPA concentration. CONCLUSIONS: EPA might be used as a new effective treatment for reversal of glucocorticoid-resistance in multiple myeloma.

Underestimated effect of the polymer encapsulation process on the photoluminescence of perovskite revealed by in situ single-particle detection.

Photostability has always been an important issue that limits the performance of organo-metal halide perovskites in optoelectronic devices. Although the photostability can be partially improved by polymer coating/encapsulation, one rising question that needs to be considered is whether the improvement of photostability is accessed at the expense of intangible loss in photoluminescence (PL) properties. By in situ analyzing the evolution of PL properties of individual perovskite crystals during the polymer encapsulation procedure, we demonstrate here that poly(methyl methacrylate), a common polymeric encapsulant, would passivate the surface defects of perovskite crystals, leading to the suppress of PL blinking. However, somewhat counterintuitive, the toluene solvent will induce the PL decline of individual perovskite crystals via accumulation of the number of quenchers that, most probably, are related to the ion migration in perovskite. The findings at the single-particle level emphasize the often-neglected role of the polymer matrix and the solvent in the optical properties of perovskite material during the polymer encapsulation process, and will guide the further design of more stable and high-performance devices based on perovskite.

Identification of bipolar disorder using a combination of multimodality magnetic resonance imaging and machine learning techniques.

BACKGROUND: Bipolar disorder (BPD) is a common mood disorder that is often goes misdiagnosed or undiagnosed. Recently, machine learning techniques have been combined with neuroimaging methods to aid in the diagnosis of BPD. However, most studies have focused on the construction of classifiers based on single-modality MRI. Hence, in this study, we aimed to construct a support vector machine (SVM) model using a combination of structural and functional MRI, which could be used to accurately identify patients with BPD. METHODS: In total, 44 patients with BPD and 36 healthy controls were enrolled in the study. Clinical evaluation and MRI scans were performed for each subject. Next, image pre-processing, VBM and ReHo analyses were performed. The ReHo values of each subject in the clusters showing significant differences were extracted. Further, LASSO approach was recruited to screen features. Based on selected features, the SVM model was established, and discriminant analysis was performed. RESULTS: After using the two-sample t-test with multiple comparisons, a total of 8 clusters were extracted from the data (VBM = 6; ReHo = 2). Next, we used both VBM and ReHo data to construct the new SVM classifier, which could effectively identify patients with BPD at an accuracy of 87.5% (95%CI: 72.5-95.3%), sensitivity of 86.4% (95%CI: 64.0-96.4%), and specificity of 88.9% (95%CI: 63.9-98.0%) in the test data (p = 0.0022). CONCLUSIONS: A combination of structural and functional MRI can be of added value in the construction of SVM classifiers to aid in the accurate identification of BPD in the clinic.

Human cortical networking by probabilistic and frequency-specific coupling.

Large-scale cortical networking patterns have been established based on the correlation of slow fluctuations of resting fMRI signals. However, the electrophysiological mechanism of cortical networking remained to be elucidated. With large-scale human ECoG recording, we developed a novel approach for functional network parcellation on the basis of probabilistic co-activation of cortical sites in spatio-temporal microstates. The parcellated networks were verified by electrical cortical stimulation (ECS) and somatosensory evoked potentials recording, which showed significantly higher accuracy than the traditional long-term correlation method. This provides direct electrophysiological evidence supporting the dynamic nature of cortical networking. Further analysis revealed that the brain-wide connectivity is likely established on the coupling of ECoG power envelop over a common carrier frequency ranging from alpha to low-beta (8-32Hz). Surprisingly, the cortical networking pattern over this specific frequency was found to be consistent across various tasks, which resembles the resting networks. The high similarity between the above functional network parcellation and the fMRI resting network atlas in individuals also suggested the slow power-envelope coupling of band-limited neural oscillations as the electrophysiological basis of spontaneous BOLD signals. Collectively, our findings on direct human recording revealed a probabilistic and frequency specific coupling mechanism for large-scale cortical networking shared by task and resting brain.

Accurate Investigation on the Fluorescence Resonance Energy Transfer between Single Organic Molecules and Monolayer WSe2 by Quantum Coherent Modulation-Enhanced Single-Molecule Imaging Microscopy.

Hybrid organic two-dimensional (2D) materials heterostructures are attracting tremendous attention for optoelectronic applications due to their low-cost processing and complementary advantages. However, accurate understanding of the fundamental physics on the interface of the hybrid heterostructures at the single-molecule level remains largely unexplored. Here, we investigated the fluorescence resonance energy transfer (FRET) between the single organic molecules and monolayer WSe2 through a newly developed single molecule microscopy technique, quantum coherent modulation-enhanced single-molecule imaging microscopy (QCME-SMIM). It is shown that the extremely weak energy transfer signal was successfully extracted from the huge fluorescence background, originating from the emission of monolayer WSe2. The observed energy transfer efficiency is in agreement with a d-4 distance dependence, with a Förster radius of ∼6 nm for the hybrid structures. Our work not only provides valuable insight into the FRET process at the single-molecule level across such hybrid organic-2D interfaces, but also demonstrates the feasibility of the newly developed technique for investigating the fundamental physics of electron transfer kinetics.

Quantum Coherent Modulation-Enhanced Single-Molecule Imaging Microscopy.

In fluorescence imaging and detection, undesired fluorescence interference (such as autofluorescence) often hampers the contrast of the image and even prevents the identification of structures of interest. Here, we develop a quantum coherent modulation-enhanced (QCME) single-molecule imaging microscopy (SMIM) to substantially eliminate the strong fluorescence interference, based on manipulation of the excited-state population probability of a single molecule. By periodically modulating the phase difference between the ultrashort pulse pairs and performing a discrete Fourier transform of the arrival time of emitted photons, the decimation of single molecules from strong interference in QCME-SMIM has been clearly determined, where the signal-to-interference ratio is enhanced by more than 2 orders of magnitude. This technique, confirmed to be universal to organic dyes and linked with biomacromolecules, paves the way to high-contrast bioimaging under unfavorable conditions.

Buyang Huanwu Decoction Attenuates Infiltration of Natural Killer Cells and Protects Against Ischemic Brain Injury.

BACKGROUND/AIMS: Natural killer (NK) cells are among the first immune cells that respond to an ischemic insult in human brains. The infiltrated NK cells damage blood-brain barrier (BBB) and exacerbate brain infarction. Buyang Huanwu Decoction (BHD), a classic Chinese traditional herbal prescription, has long been used for the treatment of ischemic stroke. The present study investigated whether BHD can prevent brain infiltration of NK cells, attenuate BBB disruption and improve ischemic outcomes. METHODS: Transient focal cerebral ischemia was induced in rats by a 60-minute middle cerebral artery occlusion, and BHD was orally administrated at the onset of reperfusion, 12 hours later, then twice daily. Assessed parameters on Day 3 after ischemia were: neurological and motor functional deficits through neurological deficit score and rotarod test, respectively; brain infarction through TTC staining; BBB integrity through Evans blue extravasation; matrix metalloproteinase-2/9 activities through gelatin zymography; tight junction protein, nuclear factor-kB (NF-kB) p65 and phospho-p65 levels through Western blotting; NK cell brain infiltration and CXCR3 levels on NK cells through flow cytometry; interferon-γ production through ELISA; CXCL10 mRNA levels through real-time PCR; CXCL10 expression and p65 nuclear translocation through immunofluorescence staining. RESULTS: BHD markedly reduced brain infarction, improved rotarod performance, and attenuated BBB breakdown. Concurrently, BHD attenuated the upregulation of matrix metalloproteinase-2/9 activities and the degradation of tight junction proteins in the ischemic brain. Infiltration of NK cells was observed in the ischemic hemisphere, and this infiltration was blunted by treatment with BHD. BHD suppressed brain ischemia-induced interferon-γ and chemokine CXCL10 production. Furthermore, BHD significantly reduced the expression of CXCR3 on brain-infiltrated NK cells. Strikingly, BHD did not affect NK cell levels or its CXCR3 expression in the spleen or peripheral blood after brain ischemia. The nuclear translocation of NF-kB p65 and phospho-p65 in the ischemic brain was inhibited by BHD. CONCLUSION: Our findings suggest that BHD prevents brain infiltration of NK cells, preserves BBB integrity and eventually improves ischemic outcomes. The inhibitory effects of BHD on NK cell brain invasion may involve its ability of suppressing NF-kB-associated CXCL10-CXCR3-mediated chemotaxis. Notably, BHD only suppresses NK cells and their CXCR3 expression in the ischemic brain, but not those in periphery.

Computational full electron structure study of biological activity in Cyclophilin A.

Cyclosporine (CsA) is widely used in organ transplant patients to help prevent the patient's body from rejecting the organ. CsA has been shown to be a safe and highly effective immunosuppressive drug that binds with the protein Cyclophilin A (CypA) at active sites. However, the exact mechanism of this binding at the molecular level remains unknown. In this project, we elucidate the binding of CsA to CypA at the molecular level by computing their electron structures and revealing their interactions. We employ a novel technique called electron Computer-Aided Drug Design (eCADD) on the protein's full electron structure along with its hydrophobic pocket and the perturbation theory of the interaction between two wave functions. We have identified the wave function of CypA, the biological active residues and active atoms of CypA and CsA, the interaction site between CypA and CsA, and the hydrogen bonds in the ligand CsA binding site. All these calculated active residues, active atoms, and hydrogen bonds are in good agreement with recorded laboratory experiments and provide guidelines for designing new ligands of CypA. We believe that our eCADD framework can provide researchers with a cost-efficient new method of drug design based on the full electron structure of proteins.

[Short-term efficacy observation on Chinese traditional medicine used after functional endoscopic sinus surgery for chronic sinusitis].

OBJECTIVE: To evaluate the efficacy of chinese traditional treatment after functional endoscopic sinus surgery (FESS) for patients with chronic sinusitis. METHOD: Eighty-eight cases of patients with chronic sinusitis were randomly divided into control group and treatment group after FESS and followed for 3 months. The control group received routine treatment. The treatment group received Chinese traditional treatment on the basis of routine treatment. VAS scores, Lund-Kennedy scores and Lund-Mackay scores were employed to conduct the subjective and objective assessment, comprehensively evaluate the clinical efficacy before and after treatment. RESULT: (1) After 3 months of treatment, the two groups of VAS scores and Lund-Mackay scores were significantly improved before treatment (P<0. 05). (2)After 3 months of treatment, the effectiveness of the control group was 81. 8%, treatment group was 97. 7%, the difference was statistically significant(P<0. 05). CONCLUSION: Chinese traditional treatment after FESS can reduce postoperative mucosal edema and promote the postoperative recovery of sinus mucosal inflammation, is effective in preventing the recurrence of postoperative.