Precision off-the-shelf natural killer cell therapies for oncology with logic-gated gene circuits.

Acute myeloid leukemia (AML) is an aggressive disease with a poor prognosis (5-year survival rate of 30.5% in the United States). Designing cell therapies to target AML is challenging because no single tumor-associated antigen (TAA) is highly expressed on all cancer subpopulations. Furthermore, TAAs are also expressed on healthy cells, leading to toxicity risk. To address these targeting challenges, we engineer natural killer (NK) cells with a multi-input gene circuit consisting of chimeric antigen receptors (CARs) controlled by OR and NOT logic gates. The OR gate kills a range of AML cells from leukemic stem cells to blasts using a bivalent CAR targeting FLT3 and/or CD33. The NOT gate protects healthy hematopoietic stem cells (HSCs) using an inhibitory CAR targeting endomucin, a protective antigen unique to healthy HSCs. NK cells with the combined OR-NOT gene circuit kill multiple AML subtypes and protect primary HSCs, and the circuit also works in vivo.

Decoding the mechanisms of chimeric antigen receptor (CAR) T cell-mediated killing of tumors: insights from granzyme and Fas inhibition.

Chimeric antigen receptor (CAR) T cell show promise in cancer treatments, but their mechanism of action is not well understood. Decoding the mechanisms used by individual T cells can help improve the efficacy of T cells while also identifying mechanisms of T cell failure leading to tumor escape. Here, we used a suite of assays including dynamic single-cell imaging of cell-cell interactions, dynamic imaging of fluorescent reporters to directly track cytotoxin activity in tumor cells, and scRNA-seq on patient infusion products to investigate the cytotoxic mechanisms used by individual CAR T cells in killing tumor cells. We show that surprisingly, overexpression of the Granzyme B (GZMB) inhibitor, protease inhibitor-9 (PI9), does not alter the cytotoxicity mediated by CD19-specific CAR T cells against either the leukemic cell line, NALM6; or the ovarian cancer cell line, SkOV3-CD19. We designed and validated reporters to directly assay T cell delivered GZMB activity in tumor cells and confirmed that while PI9 overexpression inhibits GZMB activity at the molecular level, this is not sufficient to impact the kinetics or magnitude of killing mediated by the CAR T cells. Altering cytotoxicity mediated by CAR T cells required combined inhibition of multiple pathways that are tumor cell specific: (a) B-cell lines like NALM6, Raji and Daudi were sensitive to combined GZMB and granzyme A (GZMA) inhibition; whereas (b) solid tumor targets like SkOV3-CD19 and A375-CD19 (melanoma) were sensitive to combined GZMB and Fas ligand inhibition. We realized the translational relevance of these findings by examining the scRNA-seq profiles of Tisa-cel and Axi-cel infusion products and show a significant correlation between GZMB and GZMA expression at the single-cell level in a T cell subset-dependent manner. Our findings highlight the importance of the redundancy in killing mechanisms of CAR T cells and how this redundancy is important for efficacious T cells.

A new, feasible, and convenient method based on semantic segmentation and deep learning for hemoglobin monitoring.

Objective: Non-invasive methods for hemoglobin (Hb) monitoring can provide additional and relatively precise information between invasive measurements of Hb to help doctors' decision-making. We aimed to develop a new method for Hb monitoring based on mask R-CNN and MobileNetV3 with eye images as input. Methods: Surgical patients from our center were enrolled. After image acquisition and pre-processing, the eye images, the manually selected palpebral conjunctiva, and features extracted, respectively, from the two kinds of images were used as inputs. A combination of feature engineering and regression, solely MobileNetV3, and a combination of mask R-CNN and MobileNetV3 were applied for model development. The model's performance was evaluated using metrics such as R2, explained variance score (EVS), and mean absolute error (MAE). Results: A total of 1,065 original images were analyzed. The model's performance based on the combination of mask R-CNN and MobileNetV3 using the eye images achieved an R2, EVS, and MAE of 0.503 (95% CI, 0.499-0.507), 0.518 (95% CI, 0.515-0.522) and 1.6 g/dL (95% CI, 1.6-1.6 g/dL), which was similar to that based on MobileNetV3 using the manually selected palpebral conjunctiva images (R2: 0.509, EVS:0.516, MAE:1.6 g/dL). Conclusion: We developed a new and automatic method for Hb monitoring to help medical staffs' decision-making with high efficiency, especially in cases of disaster rescue, casualty transport, and so on.

TCAF2 is associated with the immune microenvironment, promotes pathogenesis, and impairs prognosis in glioma.

PURPOSE: Glioma is the most common primary intracranial tumor and exhibits rapid growth and aggressiveness. TRPM8 channel-associated factor 2 (TCAF2), located in cell junctions and the plasma membrane, plays a key role in the pathogeneses of several cancers in humans. However, the role of TCAF2 in glioma has been elusive. METHODS: A combination of bioinformatic analysis using The Cancer Genome Atlas database and biological experiments, including 5-ethynyl-2'-deoxyuridine, transwell, and immunohistochemistry assays and xenotransplantation, was performed to analyze the expression level of TCAF2 and to mechanistically explore the relationship of TCAF2 with malignancy, prognosis, and the immune microenvironment in glioma. RESULTS: TCAF2 was upregulated in glioma, and its expression level correlated with tumor grade and clinical outcome. The role of TCAF2 in promoting glioma malignancy was characterized through in vitro and in vivo experiments. Additionally, we observed that TCAF2 can modulate the metabolic pathways and immune microenvironment. CONCLUSION: TCAF2 acts as an oncogene and may serve as a therapeutic target and prognostic marker in glioma.

Semi-supervised learning improves the performance of cardiac event detection in echocardiography.

Detection of end-diastole (ED) and end-systole (ES) frames in echocardiography video is a critical step for assessment of cardiac function. A recently released large public dataset, i.e., EchoNet-Dynamic, could be used as a benchmark for cardiac event detection. However, only a pair of ED and ES frames are annotated in each echocardiography video and the annotated ED comes before ES in most cases. This means that only a few frames during systole in each video are utilizable for training, which makes it challenging to train a cardiac event detection model using the dataset. Semi-supervised learning (SSL) could alleviate the problems. An architecture combining convolutional neural network (CNN), recurrent neural network (RNN) and fully-connected layers (FC) is adopted. Experimental results indicate that SSL brings at least three benefits: faster convergence rate, performance improvement and more reasonable volume curves. The best mean absolute errors (MAEs) for ED and ES detection are 40.2 ms (2.1 frames) and 32.6 ms (1.7 frames), respectively. In addition, the results show that models trained on apical four-chamber (A4C) view could work well on other standard views, such as other apical views and parasternal short axis (PSAX) views.

Prophylactic Administration with Methylene Blue Improves Hemodynamic Stabilization During Obstructive Jaundice-Related Diseases' Operation: a Blinded Randomized Controlled Trial.

OBJECTIVES: Patients with obstruction jaundice are at a high risk of hypotension and need high volume of fluids and a high dose of catecholamine to maintain organ perfusion during operation procedure. All these likely contribute to high perioperative morbidity and mortality. The aim of the study is to evaluate the effects of methylene blue on the hemodynamics in patients undergoing surgeries associated with obstructive jaundice. DESIGN: A prospective, randomized, and controlled clinical study. SETTING: The enrolled patients randomly received 2 mg/kg of methylene blue in saline or saline (50 ml) before anesthesia induction. The primary outcome was the frequency and dose of noradrenaline administration to maintain mean arterial blood pressure over 65 mmHg or > 80% of baseline, and systemic vascular resistance (SVR) over 800 dyne/s/cm5 during operation. The secondary outcomes were liver and kidney functions, and ICU stay. PATIENTS: Seventy patients were enrolled in the study and randomly assigned to receive either methylene blue or control (n = 35/group). RESULTS: Fewer patients received noradrenaline in the methylene blue group when compared with the control group (13/35 vs 23/35, P = 0.017), and the noradrenaline dose administrated during operation was reduced in the methylene blue group when compared with the control group (0.32 ± 0.57 mg vs 1.787 ± 3.51 mg, P = 0.018). The blood level of creatinine, glutamic oxalacetic transaminase, and glutamic-pyruvic transaminase after the operation was reduced in the methylene blue group when compared with the control group. CONCLUSIONS: Prophylactic administration of methylene blue before operation associated with obstructive jaundice improves hemodynamic stability and short-term prognosis. QUESTION: Methylene blue use prevented refractory hypotension during cardiac surgery, sepsis, or anaphylactic shock. It is still unknown that methylene blue on the vascular hypo-tone associated with obstructive jaundice. FINDINGS: Prophylactic administration with methylene blue improved peri-operative hemodynamic stability, and hepatic and kidney function on the patients with obstructive jaundice. MEANINGS: Methylene blue is a promising and recommended drug for the patients undergoing the surgeries of relief obstructive jaundice during peri-operation management.

Advantages of Transmuscular Quadratus Lumborum Block via Subfascial Approach Versus Extrafascial Approach for Postoperative Analgesia After Laparoscopic Cholecystectomy: A Randomized Controlled Study.

OBJECTIVE: We aimed to compare the analgesic effect and incidence of lower limb weakness of transmuscular quadratus lumborum (TQL) block via subfascial approach with that via extrafascial after laparoscopic cholecystectomy (LC). METHODS: Eighty patients undergoing LC were randomized to receive ultrasound-guided bilateral TQL block via subfascial (subfascial group) or extrafascial (extrafascial group) using 30 mL of 0.33% ropivacaine unilaterally. Pain scores of port sites while rest and coughing at 1, 6, 12, 24, 36, and 48 hours postoperatively as primary outcome were compared. Modified Lovett Rating Scale, ambulatory dependency, and rescue analgesia requirement was also compared. RESULTS: The pain score of the subxiphoid and of the right subcostal port site for up to the postoperative 36 hours (2 [1 to 2]) and 24 hours (2 [2 to 3]) in the subfascial group was significantly lower than that in extrafascial group (2 [2 to 2] and 3 [2.25 to 4]). Up to postoperative 24 hours, the rescue analgesia requirement in subfascial group was significantly lower than that in extrafascial group, namely less fentanyl consumption and parecoxib (1.3 [±5.5] µg vs. 5.6 [±10.6] µg; 17.5% vs. 37.5%). The ratio of patients with LRS score of 6 at postoperative 1 hour (65.0%), and with dependent ambulation at postoperative 1 and 6 hours in subfascial group (15.0% and 0.0%) was significantly lower than that in extrafascial group (10.0%, 80.0%, and 17.5%). CONCLUSION: TQL block via subfascial had the advantages of better analgesic effect and less lower limbs weakness after LC over that via extrafascial.

Host MKRN1-Mediated Mycobacterial PPE Protein Ubiquitination Suppresses Innate Immune Response.

Mycobacterium tuberculosis (Mtb), as an important intracellular pathogen, can invade and survive in macrophages and is capable of escaping the clearance of immune system. Despite decades of research efforts, the precise mechanism of immune escape and the virulence factors encoded by Mtb involved remain to be explored. Mtb-specific genomic regions of deletion (RD)-encoded proteins and PE/PPE family proteins have been implicated in immune evasion. Here, we screened more than forty RD-encoded proteins which might be involved in facilitating bacterial survival in macrophages, and found that a Mtb PPE68/Rv3873 protein, encoded by Mtb-RD1, is essential for efficient Mtb intracellular survival in macrophages. In terms of mechanism, we found that the ubiquitin ligase (E3) Makorin Ring Finger Protein 1 (MKRN1) of macrophage interacted with PPE68 and promoted the attachment of lysine (K)-63-linked ubiquitin chains to the K166 site of PPE68. K63-ubiquitination of PPE68 further bound src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP1) to suppress K63-linked polyubiquitin chains of tumor necrosis factor receptor-associated factor 6 (TRAF6), and then remarkably suppressed TRAF6-driven NF-κB and AP-1 signaling and TNF-α, IL-6 and NO production. We demonstrate that the K63-linked ubiquitination of PPE68 by MKRN1 contributed to the PPE68-mediated mycobacterial immune escape. Our finding identifies a previously unrecognized mechanism by which host MKRN1-mediated-ubiquitination of mycobacterial PPE protein suppresses innate immune responses. Disturbing the interaction between host MKRN1 ubiquitin system and mycobacterial PPE protein might be a potential therapeutic target for tuberculosis.

The Long Non-Coding RNA HOXC-AS3 Promotes Glioma Progression by Sponging miR-216 to Regulate F11R Expression.

HOXC cluster antisense RNA 3 (HOXC-AS3) is a long noncoding RNA (lncRNA) that plays a crucial role in various tumors; nevertheless, its role in glioma and its mechanism have not been completely elucidated. In this research, we discovered that HOXC-AS3 was over-expression in glioma cells and tissues and was associated with prognosis. Next, we determined that HOXC-AS3 targeted miR-216 as a sponge and that the F11 receptor (F11R) was the target of miR-216 by online databases analysis, qRT-PCR, and luciferase reporter assay. In addition, the rescue experiments confirmed that HOXC-AS3 regulated the expression of F11R by competitively binding miR-216 and functioning as a competing endogenous RNA (ceRNA). The intracranial glioblastoma mouse model suggested that HOXC-AS3 could promote glioma malignant progression in vivo. In summary, our study shows that the HOXC-AS3/miR-216/F11R axis plays an important role in the malignant progression of glioma, and may provide new ideas for the treatment of glioma.

Abnormal ECA-Binding Membrane Glycans and Galactosylated CAT and P4HB in Lesion Tissues as Potential Biomarkers for Hepatocellular Carcinoma Diagnosis.

Hepatocellular carcinoma (HCC) is one of the most common types of cancer. Despite decades of research efforts, the search for novel biomarkers is still urgently needed for the diagnosis of HCC and the improvement of clinical outcomes. Previous studies of HCC clinical biomarkers have usually focused on serum and urine samples (e.g., serum Alpha-fetoprotein (AFP). However, cellular membrane proteins in lesion tissues are less used in HCC diagnosis. The abnormal expression of membrane glycoproteins in tumor lesions are considered as potential targets for tumor diagnosis and tumor therapies. Here, a lectin array has been employed to screen and identify abnormal glycopatterns and cellular membrane glycans in HCC lesion tissues compared with adjacent non-tumor tissues. We found that there was significantly less expression of Erythrina cristagalli (ECA) lectin binding (Galß1-3/ß1-4) glycans on the cellular membrane of HCC lesion tissues compared with those of adjacent non-tumor tissues. Immunohistochemistry analysis further showed that ECA-binding ability on the membrane proteins of HCC tissues progressively decreased in different tumor-node-metastasis (TNM) stages (stage I to stage III) as the malignancy of liver cancer increased. Receiver operating curve (ROC) analysis showed ECA-binding ability yielding a sensitivity of 85% and specificity of 75%, and a combination of ECA and AFP has better clinical diagnostic efficiency, yielding a sensitivity of 90% and specificity of 85%, than ECA or AFP assay alone. ECA pull-down followed by mass spectrometry further showed that there was significantly less expression of ECA binding membrane catalase (CAT) and prolyl 4-hydroxylase beta polypeptide (P4HB) in HCC tissues compared with the adjacent non-tumor tissues. The abnormally increased expression of total CAT and P4HB and decreased expression of galactosylated membrane CAT and P4HB in HCC cell lines were correlated with an HCC metastasis status. Our findings suggest that abnormal declined ECA-binding galatosylated membrane glycans and two galactosylated-CAT and P4HB glycoproteins in lesion tissues are potential biomarkers in the diagnosis and/or metastasis prediction for HCC.

Deep weakly-supervised breast tumor segmentation in ultrasound images with explicit anatomical constraints.

Breast tumor segmentation is an important step in the diagnostic procedure of physicians and computer-aided diagnosis systems. We propose a two-step deep learning framework for breast tumor segmentation in breast ultrasound (BUS) images which requires only a few manual labels. The first step is breast anatomy decomposition handled by a semi-supervised semantic segmentation technique. The input BUS image is decomposed into four breast anatomical structures, namely fat, mammary gland, muscle and thorax layers. Fat and mammary gland layers are used as constrained region to reduce the search space for breast tumor segmentation. The second step is breast tumor segmentation performed in a weakly-supervised learning scenario where only image-level labels are available. Breast tumors are first recognized by a classification network and then segmented by the proposed class activation mapping and deep level set (CAM-DLS) method. For breast anatomy decomposition, the proposed framework achieves Dice similarity coefficient (DSC) of 83.0 ± 11.8%, 84.3 ± 10.0%, 80.7 ± 15.4% and 91.0 ± 11.4% for fat, mammary gland, muscle and thorax layers, respectively. For breast tumor recognition, the proposed framework achieves sensitivity of 95.8%, precision of 92.4%, specificity of 93.9%, accuracy of 94.8% and F1-score of 0.941. For breast tumor segmentation, the proposed framework achieves DSC of 77.3% and intersection-over-union (IoU) of 66.0%. In conclusion, the proposed framework could efficiently perform breast tumor recognition and segmentation simultaneously in a weakly-supervised setting with anatomical constraints.

Radiomics With Attribute Bagging for Breast Tumor Classification Using Multimodal Ultrasound Images.

OBJECTIVES: We aimed to develop radiomics with attribute bagging, which leverages multimodal ultrasound (US) images to improve the classification accuracy of breast tumors. METHODS: A retrospective study was conducted. B-mode US, shear wave elastographic, and contrast-enhanced US images of 178 patients with 181 tumors (67 malignant and 114 benign) were included. Radiomics with attribute bagging consisted of extraction of 1226 radiomic features and analysis of them with attribute bagging. Histologic examination results acted as the reference standard. Radiomics with several feature selection algorithms were used for comparison. Cross-validation and a holdout test were performed to evaluate their performances. RESULTS: The accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of radiomics with attribute bagging with the multimodal US images were 84.12%, 92.86%, 78.80%, and 0.919, respectively, exceeding all the comparison methods. CONCLUSIONS: Radiomics with attribute bagging combined with multimodal US images has the potential to be used for accurate diagnosis of breast tumors in the clinic.

Relationship between collectivism and corruption in American and Chinese books: A historical perspective.

Previous research on the relationship between collectivism and corruption has not investigated their co-variation over time. In this study, we use Google Ngram Viewer to track the frequency of words related to collectivism and corruption in American books (1800-2000) and in Chinese Books (1970-2008). The results demonstrate that a positive association between the usage of these terms during the periods in both Chinese and American books, with changes in words related to collectivism preceding changes in words related to corruption in American books. The theoretical and practical implications are also discussed.

Quantitative evaluation of graded hindlimb ischemia based on pharmacokinetic modelling and hemodynamic analysis of indocyanine green.

OBJECTIVE: Accurate evaluation of the degree of hindlimb ischemia is challenging but essential for the diagnosis and treatment of peripheral vascular insufficiency. The aim of the study is to apply a multiparametric method for the quantitative estimation of mouse models with different degrees of hindlimb ischemia based on a dynamic fluorescence imaging-based strategy. APPROACH: An adjustable hydraulic occluder was placed around the thigh root of one hindlimb to induce six different degrees of hindlimb ischemia. Five parameters were extracted to quantitatively evaluate the degree of ischemia, including perfusion rate (PR) and perfusion vascular density (PVD) from a mathematical model of indocyanine green (ICG) pharmacokinetics, rising time (T rise), blood flow index (BFI) and mean fluorescence intensity (MFI) from time-series analysis of ICG hemodynamics. MAIN RESULTS: The results showed that the normalized PR and BFI decreased while the normalized T rise increased progressively with the degree of ischemia. The normalized PVD and MFI first increased and then decreased with the degree of ischemia. High correlation was observed between the degree of ischemia and the arterial oxygen saturation which was measured by an oximeter. SIGNIFICANCE: The results of this work demonstrated that PR, BFI and T rise can be used for the quantitative and comprehensive evaluation of graded hindlimb ischemia.

Electrocardiogram Signal Denoising Using Extreme-Point Symmetric Mode Decomposition and Nonlocal Means.

Electrocardiogram (ECG) signals contain a great deal of essential information which can be utilized by physicians for the diagnosis of heart diseases. Unfortunately, ECG signals are inevitably corrupted by noise which will severely affect the accuracy of cardiovascular disease diagnosis. Existing ECG signal denoising methods based on wavelet shrinkage, empirical mode decomposition and nonlocal means (NLM) cannot provide sufficient noise reduction or well-detailed preservation, especially with high noise corruption. To address this problem, we have proposed a hybrid ECG signal denoising scheme by combining extreme-point symmetric mode decomposition (ESMD) with NLM. In the proposed method, the noisy ECG signals will first be decomposed into several intrinsic mode functions (IMFs) and adaptive global mean using ESMD. Then, the first several IMFs will be filtered by the NLM method according to the frequency of IMFs while the QRS complex detected from these IMFs as the dominant feature of the ECG signal and the remaining IMFs will be left unprocessed. The denoised IMFs and unprocessed IMFs are combined to produce the final denoised ECG signals. Experiments on both simulated ECG signals and real ECG signals from the MIT-BIH database demonstrate that the proposed method can suppress noise in ECG signals effectively while preserving the details very well, and it outperforms several state-of-the-art ECG signal denoising methods in terms of signal-to-noise ratio (SNR), root mean squared error (RMSE), percent root mean square difference (PRD) and mean opinion score (MOS) error index.

Dorsalis pedis arterial pressure is lower than noninvasive arm blood pressure in normotensive patients under sevoflurane anesthesia.

BACKGROUND: It is widely known that blood pressure (BP) in the lower extremity is higher than in the upper extremity. However, whether this phenomenon remains the same during general anesthesia is still unclear. This study aims to investigate the difference between invasive dorsalis pedis artery (DPA) pressure and the most commonly used noninvasive arm pressure during sevoflurane anesthesia. METHODS: A total of 50 normotensive Chinese patients were enrolled in this observational study. Invasive DPA pressure, noninvasive arm pressure, and systemic vascular resistance index were assessed simultaneously. BP data during the entire surgery were analyzed through a Bland-Altman plot for repeated measures. The concordance of BP variation in the DPA and the arm was analyzed using four-quadrant plots and linear regression. The time-dependent changes in BP and the systemic vascular resistance index were also evaluated. RESULTS: Data from 46 effective cases were analyzed. Bias (95% limits of agreement) was -7.40 mmHg (-20.36 to +5.57 mmHg) for mean blood pressure, +3.54 mmHg (-20.32 to +27.41 mmHg) for systolic blood pressure, and -10.20 mmHg (-23.66 to +3.26 mmHg) for diastolic blood pressure, respectively. The concordance of BP variation at the two measurement sites was clinically acceptable. DPA pressure and vascular resistance in the lower limb decreased gradually during surgery. CONCLUSION: DPA pressure tends to be lower than arm pressure under sevoflurane anesthesia, especially the mean blood pressure and the diastolic blood pressure. Hence, noninvasive arm BP monitoring is recommend to be retained when invasive BP is measured at the DPA, so as to allow clinicians to comprehensively evaluate the BP condition of the patients and make appropriate therapeutic decisions.

Gradient between dorsalis pedis and radial arterial blood pressures during sevoflurane anaesthesia: A self-control study in patients undergoing neurosurgery.

BACKGROUND: The dorsalis pedis artery (DPA) is a good alternative to the radial artery (RA) for invasive blood pressure monitoring when the upper limb is burned or injured, or if the RA is not available. Understanding the pattern of pressure difference between DPA and the commonly used RA during inhalational anaesthesia is helpful for haemodynamic management and therapeutic decisions. OBJECTIVES: The objective of this study was to investigate the time-dependent variation of DPA-to-RA pressure gradient during sevoflurane anaesthesia and the overall difference between the two pressures during neurosurgery, together with the causes of the pressure gradient change. DESIGN: A prospective, self-control, single-centre study. SETTING: The operating room of a teaching hospital from 1 January 2013 to 1 September 2013. PATIENTS: Thirty-seven patients between 18 and 60 years of age, American Society of Anesthesiologists' physical status 1-3, scheduled for neurosurgery in the supine position and requiring invasive arterial pressure monitoring. MAIN OUTCOME MEASURES: The time-dependent change of DPA-to-RA pressure gradient and skin temperature gradient, the difference between absolute values and average values of SBP, DBP and mean blood pressure (MBP) between RA and DPA during surgery, and the internal cross-sections and systolic blood flow velocities of RA and DPA at the baseline and at the end of surgery. RESULTS: Data from 30 patients were analysed. The mean ±â€Šstandard deviation DPA-to-RA pressure gradient gradually decreased with time from 9.7 ±â€Š8.8 to -1.8 ±â€Š7.6 mmHg for systolic pressure, -2.3 ±â€Š2.7 to -3.7 ±â€Š2.8 mmHg for diastolic pressure and -2.1 ±â€Š3.2 to -5.4 ±â€Š3.4 mmHg for MBP. Biases during the entire procedure were 2.2 ±â€Š10.1, -3.1 ±â€Š3.4 and -4.3 ±â€Š4.2 mmHg for SBP, DBP and MBP, respectively. The DPA-to-RA skin temperature gradient gradually reduced from -3.6 ±â€Š2.4 to -1.1 ±â€Š1.3°C. A greater increase in the inner cross-sectional area and blood flow from the baseline was observed at DPA compared with RA. CONCLUSION: The blood pressure, temperature and inner cross-sectional area differences between DPA and RA reduced gradually during sevoflurane anaesthesia in patients undergoing neurosurgery. Therapeutic decisions may rely on DPA pressure as long as the anaesthetists are aware of the pattern of change in DPA pressure during surgery. TRIAL REGISTRATION: www.chictr.org with registry number ChiCTR-RNRC-13003853.

The Relationship between Cultural Anxiety and Ethnic Essentialism: The Mediating Role of an Endorsement of Multicultural Ideology.

Many studies have explored the social consequences of ethnic essentialism in recent decades. In addition, a few studies have focused on the impact of perceived cultural context on ethnic essentialism. However, it is not clear why perceived cultural context can lead to changes in ethnic essentialism. In the present study, we hypothesized that the cultural anxiety of ethnic minorities may trigger a strong endorsement of and support for a multicultural ideology, thereby affecting beliefs about ethnic groups. To address the issue, 226 Tibetan and 102 Hui college students from Mainland China completed our questionnaires. The results across the two samples showed that (1) cultural anxiety was positively associated with both the endorsement of a multicultural ideology and ethnic essentialism, (2) cultural anxiety and the endorsement of a multicultural ideology positively predicted ethnic essentialism after controlling for demographic variables, and (3) cultural anxiety had both a direct effect on ethnic essentialism and an indirect effect on ethnic essentialism through the endorsement of a multicultural ideology. Our findings suggest that when ethnic minorities experience cultural anxiety, they might endorse a multicultural ideology and adopt essentialism to affirm their ethnic identities.

[The study of photo-elastic modulator-based Fourier transform spectroscopy].

In order to enhance the spectrum resolution of current photo-elastic modulator-based Fourier transform spectrometer, a multi-reflected photo-elastic modulator-based interferometer structure was proposed in the present paper. Through coating reflecting film alternatingly on the photo-elastic crystal and light oblique incidence, and allowing the incident ray to have the multi-reflection in the crystal and exit from the other side of the crystal, the authors increased the light propagation distance in the crystal and enhanced the optical path difference at last. Based on this, the function of interference-spectrum retrieval was established, the optical system matched to the multi-reflected PEM-based interferometer was designed, and finally, the experimental system of multi-reflected PEM-based Fourier transform spectroscopy for telemetry was established. The principle of verification tests by using 671 nm laser and xenon lamp shows that the interferogram was clear and stable, and the feasibility of the principle of the system was verified. The expected result shows that the spectrum resolution of the designed PEM-FTs with multi-reflection achieved 13 cm(-1), and its luminous flux just didn't reduce too much, which ensured the SNR. Through spectral inversion of the interference fringes, the technical feasibility of the spectrum system developed was verified. This work established the basic condition of prototype fabrication, radiation precise calibration, spectral calibration and instrument signal-to-noise ratio test and so on.

MiR-206 controls the phenotypic modulation of pulmonary arterial smooth muscle cells induced by serum from rats with hepatopulmonary syndrome by regulating the target gene, annexin A2.

BACKGROUND: Hepatopulmonary syndrome (HPS) is a serious complication of advanced liver disease that is characterised by intrapulmonary vascular dilatation (IPVD) and arterial hypoxemia. Pulmonary vascular remodelling (PVR) is an important pathological feature of HPS, but the potential mechanisms underlying PVR remain undefined. Recent findings have established the essential role of changes in Annexin A2 (ANXA2) in controlling the phenotypic modulation of pulmonary artery smooth muscle cells (PASMCs) in PVR associated with HPS. However, the mechanism by which upstream signalling regulates ANXA2 is unclear. METHODS: In the present study, computational analysis was used to predict which miRNA might target the 3´-untranslated region (3´-UTR) of the ANXA2 mRNA. Real-time PCR and western blotting were performed to study the level of correlation between ANXA2 and the differentiation marker with the predicted miRNAs in PASMCs stimulated with serum from normal rats or those with HPS. Functional analysis of the miRNA and a luciferase reporter assay were performed to demonstrate that the predicted miRNA suppressed ANXA2 expression by directly targeting the predicted 3´-UTR site of the ANXA2 mRNA. RESULTS: Computational analysis predicted that miR-206 would target the 3´-UTR of ANXA2 mRNA. In HPS rat serum-stimulated PASMCs, the expression of miR-206 displayed an inverse correlation with ANXA2, while a positive correlation was observed with the phenotypic marker smooth muscle α-actin (SM α-actin). The miRNA functional analysis and luciferase reporter assay demonstrated that miR-206 effectively downregulated the expression of ANXA2 by binding to the 3´-UTR of the ANXA2 mRNA. Consistently, miR-206 effectively inhibited the HPS rat serum-induced phenotypic modulation and proliferation, while these effects were reversed in ANXA2-overexpressing PASMCs. CONCLUSION: This study demonstrates that miR-206 inhibits the HPS rat serum-induced phenotypic modulation and proliferation in PASMCs by down-regulating ANXA2 gene expression.