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This study aims to find out the possible optimal therapy and assess the prognosis properly for patient with spontaneous rupture of hepatocellular carcinoma (HCC).Propensity score matching (PSM) analysis was used to study the data from 325 patients with ruptured HCC (RHCC) and 2,291 patients with non-RHCC.The incidence and hospital mortality of RHCC were 5.1% and 0.8% respectively, with a median overall survival (OS) time of 17 months. There was no difference between ruptured and non-RHCC patients undergoing conservation treatment in terms of OS. Trans-arterial embolization (TAE) was carried out in 69 (21.2%) cases with RHCC, with a median OS of 7 months, which was no difference from that of non-RHCC (pre- and post-PSM). One hundred and sixty-nine (52.0%) RHCC cases underwent one-stage hepatectomy, with a median OS and disease-free survival (DFS) of 30 and 6 months respectively, which were shorter than that of non-RHCC (post-PSM). TAE plus two-stage hepatectomy was performed in 30 RHCC cases, with a median OS and DFS of 28 and 10 months respectively; these outcomes were better than that from RHCC patients undergoing TAE alone or one-stage hepatectomy (post-PSM), which were no difference from that of non-RHCC patients undergoing hepatectomy. The risk of death for RHCC patient undergoing one-stage hepatectomy is 1.545 times higher than that of one undergoing TAE + two-stage hepatectomy.TAE plus two-stage hepatectomy might be the optimal treatment for RHCC patient. Under the premise of the same pathological properties, there is no difference in prognosis between ruptured and non-RHCC patients if the therapy is appropriate.

The accumulation of soluble β-amyloid aggregates (sAβs) is one of the main culprits in Alzheimer’s disease (AD) progression, which can lead to synaptic dysfunction and subsequent neurodegeneration....

Breast cancer diagnosed within 10 years following childbirth is defined as postpartum breast cancer (PPBC) and is highly metastatic. Interactions between immune cells and other stromal cells within the involuting mammary gland are fundamental in facilitating an aggressive tumor phenotype. The MNK1/2–eIF4E axis promotes translation of prometastatic mRNAs in tumor cells, but its role in modulating the function of nontumor cells in the PPBC microenvironment has not been explored. Here, we used a combination of in vivo PPBC models and in vitro assays to study the effects of inactivation of the MNK1/2–eIF4E axis on the protumor function of select cells of the tumor microenvironment. PPBC mice deficient for phospho-eIF4E (eIF4ES209A) were protected against lung metastasis and exhibited differences in the tumor and lung immune microenvironment compared with wild-type mice. Moreover, the expression of fibroblast-derived IL33, an alarmin known to induce invasion, was repressed upon MNK1/2–eIF4E axis inhibition. Imaging mass cytometry on PPBC and non-PPBC patient samples indicated that human PPBC contains phospho-eIF4E high–expressing tumor cells and CD8+ T cells displaying markers of an activated dysfunctional phenotype. Finally, inhibition of MNK1/2 combined with anti–PD-1 therapy blocked lung metastasis of PPBC. These findings implicate the involvement of the MNK1/2–eIF4E axis during PPBC metastasis and suggest a promising immunomodulatory route to enhance the efficacy of immunotherapy by blocking phospho-eIF4E. Significance: This study investigates the MNK1/2–eIF4E signaling axis in tumor and stromal cells in metastatic breast cancer and reveals that MNK1/2 inhibition suppresses metastasis and sensitizes tumors to anti–PD-1 immunotherapy.

Smoking and Candida albicans (C. albicans) infection are risk factors for many oral diseases. Several studies have reported a close relationship between smoking and the occurrence of C. albicans infection. However, the exact underlying mechanism of this relationship remains unclear. We established a rat infection model and a C. albicans‐Leuk1 epithelial cell co‐culture model with and without smoke exposure to investigate the mechanism by which smoking contributes to C. albicans infection. Oral mucosa samples from healthy individuals and patients with oral leucoplakia were also analysed according to their smoking status. Our results indicated that smoking induced oxidative stress and redox dysfunction in the oral mucosa. Smoking‐induced Nrf2 negatively regulated the NLRP3 inflammasome, impaired the oral mucosal defence response and increased the oral mucosa susceptibility to C. albicans. The results suggest that the Nrf2 pathway could be involved in the pathogenesis of oral diseases by mediating an antioxidative response to cigarette smoke exposure and suppressing host immunity against C. albicans.

The ever-increasing space exploration enterprise calls for novel and high-quality radiation-resistant materials, among which nonlinear optical materials and devices are particularly scarce. Two-dimensional (2D) materials have shown promising potential, but the radiation effects on their nonlinear optical properties remain largely elusive. We previously fabricated 2D bismuthene for mode-locking sub-ns laser; herein, their space adaption was evaluated under a simulated space radiation environment. The as-synthesized thin layers of bismuthene exhibited strong third-order nonlinear optical responses extending into the near-infrared region. Remarkably, when exposed to 60Co γ-rays and electron irradiation, the bismuthene showed only slight degradation in saturable absorption behaviors that were critical for mode-locking in space. Ultrafast spectroscopy was applied to address the radiation effects and damage mechanisms that are difficult to understand by routine techniques. This work offers a new bottom-up approach for preparing 2D bismuthene, and the elucidation of its fundamental excited-state dynamics after radiation also provides a guideline to optimize the material for eventual space applications.

Background Despite the increasing research on low back pain, the bibliometric literature in the field of low back pain is limited. The aim of this study was to perform a bibliometric and visualization analysis of low back pain. Methods The authors searched the Web of Science database to extract publications regarding low back pain in the last 22 years. A total of 12,201 publications were eligible. We classified and analyzed publications such as total citations, average citations per item, H-index, research types, countries/regions, institutions and journals by using standard bibliometric indicators. Bibliometric methods and tools were used to explore the trends of low back pain research. Results Over the past 22 years, the number of publications on low back pain in the world had continually remained a increasing trend. Regional differences existed in the research of low back pain and developed countries played a leading role in the research. Research institutions and researchers have successively invested in the research of low back pain. However, there were limitations to the present study that should be noted that the study was relatively scattered and a systematic summary of the trends and characteristics was lacking. Visualization analysis provides valuable information for researchers to identify new perspectives on potential collaborators and cooperative institutions, which promote indirect cooperation. Besides, the most burst keywords were “primary-care”, “lumbar spine” and “disability”. Conclusion This study provided a number of important insights into the global research trends and current status related to low back pain which is helpful for clinicians, researchers and policy makers to understand the research field and predict its dynamic directions. Our article could be used for quantify and academic publications about low back pain in order to obtain an overview of the given field of study and provide references and suggestions for the future work of low back pain.

Aims Morphological abnormalities are present in patients with developmental dysplasia of the hip (DDH). We studied and compared the pelvic anatomy and morphology between the affected hemipelvis with the unaffected side in patients with unilateral Crowe type IV DDH using 3D imaging and analysis. Methods A total of 20 patients with unilateral Crowe-IV DDH were included in the study. The contralateral side was considered normal in all patients. A coordinate system based on the sacral base (SB) in a reconstructed pelvic model was established. The pelvic orientations (tilt, rotation, and obliquity) of the affected side were assessed by establishing a virtual anterior pelvic plane (APP). The bilateral coordinates of the anterior superior iliac spine (ASIS) and the centres of hip rotation were established, and parameters concerning size and volume were compared for both sides of the pelvis. Results The ASIS on the dislocated side was located inferiorly and anteriorly compared to the healthy side (coordinates on the y-axis and z-axis; p = 0.001; p = 0.031). The centre of hip rotation on the dislocated side was located inferiorly and medially compared to the healthy side (coordinates on the x-axis and the y-axis; p < 0.001; p = 0.003). The affected hemipelvis tilted anteriorly in the sagittal plane (mean 8.05° (SD 3.57°)), anteriorly rotated in the transverse plane (mean 3.31° (SD 1.41°)), and tilted obliquely and caudally in the coronal plane (mean 2.04° (SD 0.81°)) relative to the healthy hemipelvis. The affected hemipelvis was significantly smaller in the length, width, height, and volume than the healthy counterpart. (p = 0.014; p = 0.009; p = 0.035; p = 0.002). Conclusion Asymmetric abnormalities were identified on the affected hemipelvis in patients with the unilateral Crowe-IV DDH using 3D imaging techniques. Improved understanding of the morphological changes may influence the positioning of the acetabular component at THA. Acetabular component malpositioning errors caused by anterior tilt of the affected hemi pelvis and the abnormal position of the affected side centre of rotation should be considered by orthopaedic surgeons when undertaking THA in patients with Crowe-IV DDH. Cite this article: Bone Joint J 2020;102-B(10):1311–1318.

The purpose of this study was to investigate the antitumor mechanisms of n-butylidenephthalide (BP) and to further examine the delivery efficacy of polycationic liposome containing PEI and polyethylene glycol complex (LPPC)-encapsulated BP in leukemia cells. MTS, flow cytometric and TUNEL assays were performed to assess cell viability and apoptosis. BP and BP/LPPC complex delivery efficiency was analyzed by full-wavelength fluorescent scanner and fluorescence microscope. The expressions of cell cycle- and apoptosis-related proteins were conducted by Western blotting. The results showed that BP inhibited leukemia cell growth by inducing cell cycle arrest and cell apoptosis. LPPC-encapsulated BP rapidly induced endocytic pathway activation, resulting in the internalization of BP into leukemia cells, causing cell apoptosis within 1 h. LPPC encapsulation enhanced the cytotoxic activity of BP and did not influence the effects of BP induction that suggested LPPC-encapsulated BP might be developed as anti-leukemia drugs in future.

Aims/hypothesis Retinal microvascular diameters are biomarkers of cardio-metabolic risk. However, the association of (pre)diabetes with retinal microvascular diameters remains unclear. We aimed to investigate the association of prediabetes (impaired fasting glucose or impaired glucose tolerance) and type 2 diabetes with retinal microvascular diameters in a predominantly white population. Methods In a population-based cohort study with oversampling of type 2 diabetes (N = 2876; n = 1630 normal glucose metabolism [NGM], n = 433 prediabetes and n = 813 type 2 diabetes, 51.2% men, aged 59.8 ± 8.2 years; 98.6% white), we determined retinal microvascular diameters (measurement unit as measured by retinal health information and notification system [RHINO] software) and glucose metabolism status (using OGTT). Associations were assessed with multivariable regression analyses adjusted for age, sex, waist circumference, smoking, systolic blood pressure, lipid profile and the use of lipid-modifying and/or antihypertensive medication. Results Multivariable regression analyses showed a significant association for type 2 diabetes but not for prediabetes with arteriolar width (vs NGM; prediabetes: β = 0.62 [95%CI −1.58, 2.83]; type 2 diabetes: 2.89 [0.69, 5.08]; measurement unit); however, there was a linear trend for the arteriolar width across glucose metabolism status (p for trend = 0.013). The association with wider venules was not statistically significant (prediabetes: 2.40 [−1.03, 5.84]; type 2 diabetes: 2.87 [−0.55, 6.29], p for trend = 0.083; measurement unit). Higher HbA1c levels were associated with wider retinal arterioles (standardised β = 0.043 [95% CI 0.00002, 0.085]; p = 0.050) but the association with wider venules did not reach statistical significance (0.037 [−0.006, 0.080]; p = 0.092) after adjustment for potential confounders. Conclusions/interpretation Type 2 diabetes, higher levels of HbA1c and, possibly, prediabetes, are independently associated with wider retinal arterioles in a predominantly white population. These findings indicate that microvascular dysfunction is an early phenomenon in impaired glucose metabolism.

Lu Ding, Yu-Hang Gao, Ye-Ran Li, Yi-Fan Huang, Xin-Yu Wang, Xin Qi Department of Orthopaedic Surgery, The First Hospital of Jilin University, Jilin University, Chang Chun, People’s Republic of ChinaCorrespondence: Xin QiDepartment of Orthopaedic Surgery, The First Hospital of Jilin University, Jilin University, Xinmin St 71, Chang Chun, People’s Republic of ChinaTel +8615843073202Fax +86043181875600Email qixindoc@163.comPurpose: This study was to evaluate the metabolic score for insulin resistance (METS-IR) in female knee osteoarthritis (KOA) patients in a Chinese population. The associations between METS-IR and adipokines, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were investigated.Patients and Methods: This study included 4686 women from the 2011 China Health and Retirement Longitudinal Study (CHARLS) and 108 women who underwent arthroplasty of KOA at a university hospital. The clinical data were collected, and adipokines were evaluated. METS-IR was calculated in the KOA patients and compared with the national baseline. Logistic regression analyses were applied to explore the associations of METS-IR with adipokines, ESR, and CRP.Results: Receiver operating characteristic curve analysis of METS-IR and metabolic syndrome (MetS) in national baseline showed an area under the curve value of 0.851, with sensitivity of 0.777 and specificity of 0.772. The METS-IR of KOA was higher than the national baseline level (40.29 ± 6.98 vs 36.20 ± 8.50, P < 0.01), even after adjusting age. In addition, the METS-IR was higher in patients with KOA who had MetS than in those without metabolic syndrome (nMetS), even after adjusting body mass index (BMI). After adjusting for age and BMI, METS-IR was associated with CRP (OR 1.238, 95% confidence interval (CI) 1.088, 1.409, P < 0.01), ESR (OR 1.124, 95% CI 1.008, 1.254, P = 0.036), plasma leptin (OR 1.123, 95% CI 1.052, 1.199, P < 0.01), plasma resistin (OR 1.134, 95% CI 1.011, 1.271, P = 0.031), and plasma adiponectin (OR 0.865, 95% CI 0.771, 0.971, P = 0.014).Conclusion: METS-IR in female KOA was higher than that of the national baseline. The METS-IR was related to adipokine disorder and inflammatory activity. These findings suggest that METS-IR can be used to evaluate the degree of involvement of MetS in KOA.Keywords: knee osteoarthritis, metabolic syndrome, insulin resistance, metabolic score for insulin resistance

AIM The incidence of placenta previa before the third trimester is high. But many cases resolve as pregnancy progresses. Our study was to evaluate the efficacy of uterine artery Doppler velocimetry at mid-term gestation for predicting placenta previa resolution in third trimester. METHODS A single-center retrospective study was done. A study cohort of 504 subjects with placenta-cervix os distance measured both at 22-24 weeks and after 36 weeks of gestation and uterine artery Doppler velocimetry measured at 22-24 weeks of gestation were selected. The subjects were assigned to control group (n = 351), resolving group (n = 89) and placenta previa group (n = 64) according to their diagnosis of placenta previa at mid-term and the end of the third trimester. The averages of the bilateral ratio of uterine artery systolic to end-diastolic maximum blood flow velocity (S/D ratio), pulsatility index (PI) and resistance index (RI) were used for analysis. RESULTS The means of S/D ratio, PI and RI of uterine arteries in the placenta previa group were significantly lower than that in either control group or resolving group. No differences were observed between control group and resolving group. The areas under the receiver operating characteristic curve were 0.7632, 0.7579 and 0.7644 for the means of S/D ratio, PI and RI, respectively (P

The rapid development of portable spectrometers has evoked a large demand for minimized light sources; meanwhile, NIR phosphor-converted light-emitting diodes (NIR pc-LEDs) are an optimal choice due to their compactness and low cost. The phosphors used in NIR spectroscopy (NIRS) are required to have broadband emission and high quantum efficiency (QE) for a wider detection range and efficient photo-to-electricity conversion. Inspired by the structural tunability of Y3Al5O12 (YAG), we proposed to achieve broadband emission by crystal field engineering, i.e., indirectly regulating the crystal field strength of Cr3+via the co-substitution of Y3+–Al3+ by Ca2+–Si4+ in YAG. The crystal field strength experienced on Cr3+ decreased as the octahedron was distorted and enlarged by the co-substitution. A broadband NIR emission with a large full width at half maximum (FWHM) of 160 nm and a high internal quantum efficiency (IQE) of ∼75.9% was realized in Y3−xCaxAl5−xSixO12:0.6% Cr (x = 1). The suitability of the investigated NIR phosphor was demonstrated by fabricating an NIR pc-LED prototype, and the detection resolution was improved by 30% compared to that of a traditional white pc-LED. These results indicate the great potential of the Y2CaAl4SiO12:Cr phosphors for use in highly precise and sensitive NIR pc-LEDs.

Background Coronaviruses can be isolated from bats, civets, pangolins, birds and other wild animals. As an animal-origin pathogen, coronavirus can cross species barrier and cause pandemic in humans. In this study, a deep learning model for early prediction of pandemic risk was proposed based on the sequences of viral genomes. Methods A total of 3257 genomes were downloaded from the Coronavirus Genome Resource Library. We present a deep learning model of cross-species coronavirus infection that combines a bidirectional gated recurrent unit network with a one-dimensional convolution. The genome sequence of animal-origin coronavirus was directly input to extract features and predict pandemic risk. The best performances were explored with the use of pre-trained DNA vector and attention mechanism. The area under the receiver operating characteristic curve (AUROC) and the area under precision-recall curve (AUPR) were used to evaluate the predictive models. Results The six specific models achieved good performances for the corresponding virus groups (1 for AUROC and 1 for AUPR). The general model with pre-training vector and attention mechanism provided excellent predictions for all virus groups (1 for AUROC and 1 for AUPR) while those without pre-training vector or attention mechanism had obviously reduction of performance (about 5–25%). Re-training experiments showed that the general model has good capabilities of transfer learning (average for six groups: 0.968 for AUROC and 0.942 for AUPR) and should give reasonable prediction for potential pathogen of next pandemic. The artificial negative data with the replacement of the coding region of the spike protein were also predicted correctly (100% accuracy). With the application of the Python programming language, an easy-to-use tool was created to implements our predictor. Conclusions Robust deep learning model with pre-training vector and attention mechanism mastered the features from the whole genomes of animal-origin coronaviruses and could predict the risk of cross-species infection for early warning of next pandemic. Graphical Abstract

Background:. Postoperative pneumonia (POP) is one of the most common infections following heart valve surgery (HVS) and is associated with a significant increase in morbidity, mortality, and health care costs. This study aimed to identify the major risk factors associated with the occurrence of POP following HVS and to derive and validate a clinical risk score. Methods:. Adults undergoing open HVS between January 2016 and December 2019 at a single institution were enrolled in this study. Patients were randomly assigned to the derivation and validation sets at 1:1 ratio. A prediction model was developed with multivariable logistic regression analysis in the derivation set. Points were assigned to independent risk factors based on their regression coefficients. Results:. POP occurred in 316 of the 3853 patients (8.2%). Multivariable analysis identified ten significant predictors for POP in the derivation set, including older age, smoking history, chronic obstructive pulmonary disease, diabetes mellitus, renal insufficiency, poor cardiac function, heart surgery history, longer cardiopulmonary bypass, blood transfusion, and concomitant coronary and/or aortic surgery. A 22-point risk score based on the multivariable model was then generated, demonstrating good discrimination (C-statistic: 0.81), and calibration (Hosmer-Lemeshow χ2 = 8.234, P = 0.312). The prediction rule also showed adequate discriminative power (C-statistic: 0.83) and calibration (Hosmer-Lemeshow χ2 = 5.606, P = 0.691) in the validation set. Three risk intervals were defined as low-, medium-, and high-risk groups. Conclusion:. We derived and validated a 22-point risk score for POP following HVS, which may be useful in preventive interventions and risk management. Trial Registration:. Chictr.org, ChiCTR1900028127; http://www.chictr.org.cn/showproj.aspx?proj=46932

Melanoma is the deadliest form of skin cancer. Although targeted therapies and immunotherapies have revolutionized the treatment of metastatic melanoma, most patients are not cured. Therapy resistance remains a significant clinical challenge. Melanoma comprises phenotypically distinct subpopulations of cells, exhibiting distinct gene signatures leading to tumor heterogeneity and favoring therapeutic resistance. Cellular plasticity in melanoma is referred to as phenotype switching. Regardless of their genomic classification, melanomas switch from a proliferative and differentiated phenotype to an invasive, dedifferentiated and often therapy-resistant state. In this review we discuss potential mechanisms underpinning melanoma phenotype switching, how this cellular plasticity contributes to resistance to both targeted therapies and immunotherapies. Finally, we highlight novel strategies to target plasticity and their potential clinical impact in melanoma.

Objective To evaluate the methodological quality of Tuina clinical practice guidelines. Methods Computer searches of China National Knowledge Infrastructure (CNKI), Chinese Technical Periodicals (VIP), Wanfang Data Knowledge Service Platform, PubMed, Cochrane Library, Embase, and other databases were conducted to search for published guidelines on Tuina, with a search time frame from database creation to March 2021. Four evaluators independently used the Appraisal of Guidelines for Research and Evaluation II instrument to evaluate the quality of the included guidelines.Results Eight guidelines related to Tuina were included in this study. The quality of reporting was low in all included guidelines. The highest quality report had a total score of 404 and was rated as "highly recommended". The worst guideline had a final score of 241 and was rated as "not recommended". Overall, 25% of the included guidelines were recommended for clinical use, 37.5% were recommended after revision, and 37.5% were not recommended for use.Conclusion The number of existing Tuina clinical practice guidelines is limited. The methodological quality is low, far from the internationally accepted norms of clinical practice guideline development and reporting. In the future development of Tuina guidelines, emphasis should be placed on the reporting specifications of guidelines and the methodology of guideline development, including the rigor of the guideline development process, the clarity, application, and independence of reporting, to improve the quality and applicability of clinical practice guidelines, to guide and standardize the clinical practice of Tuina.

Lithium ion capacitors (LICs) are energy storage devices integrating the complementary features of both supercapacitors and lithium ion batteries to simultaneously reach high energy and power densities. One of the major challenges in LIC technology is the kinetic imbalance between the faradaic insertion anode and capacitive cathode. Therefore, the design of electrode materials is crucial to enhance the rate performance of anode and the capacitance of the cathode in LIC devices. In this work, novel LICs were demonstrated with nanostructured cathode and anode. A vertically-aligned carbon nanoflakes (VACNFs) cathode provided high electrochemically active surface area and excellent conductivity, while a metal organic framework (MOF) derived carbonized nickel cobalt oxide (cNiCo2O4) anode ensured fast conversion reactions and remarkable cyclability. Electrochemical characterization of individual electrode confirmed that both electrodes exhibited good electron and ion transport capability. The LICs were fabricated with optimized electrode active materials loading to deliver high energy densities at desired charge/discharge rates. The devices exhibited energy density up to 136.9 W h/kg (at 200 W/kg). At higher power density of 40 kW/kg, under which a full charge-discharge can be finished within 4 s, the LICs could still deliver an energy density of 26.44 W h/kg. The devices also showed a good cycle stability (≈90% capacitance retention after 9000 cycles, under current density of 4 A/g) within the voltage range of 1–4.2 V.

Complete surface passivation of CsPbBr3 quantum dots by treatment with di-dodecyldimethylammonium bromide and sodium thiocyanate is demonstrated resulting in dispersions with photostable photoluminescence of near-unity quantum yield and a lifetime of 17.5 ns. Before treatment, the photoluminescence has a quantum yield of 73% and lifetime of 9.4 ns, and decayed by 80% on exposure to ultraviolet light for an hour. When used as the photo-emitting species in a solution-processed LED structure, the surface treatment increased the maximum luminance from 550 cd.m-2 to 1200 cd.m-2, and reduced the turn-on voltage from 3.1 V to 2.8 V.

Objective: To evaluate the expression levels of adipokines in the synovium and infrapatellar fat pad (IPFP) in osteoarthritis (OA) patients with and without metabolic syndrome (MetS). Methods: 120 female patients with OA were enrolled, and 60 healthy women matched body mass index, age, and sex, served as controls. Adipokines levels were measured using a sandwich enzyme-linked immunosorbent assay of the serum of all participants and synovial fluid (SF) of OA patients. Local expression levels of adipokines in the synovium and IPFP were examined by immunohistochemical analysis. The amount of adipokine proteins was analyzed using Western blot, and adipokine mRNA expressions were determined via quantitative real-time polymerase chain reaction (qRT-PCR). Results: Serum leptin levels were significantly higher in the non-MetS-OA group than those in controls (7.97 vs. 4.24 ng/ml, p< 0.001), and even higher leptin levels were found in the MetS-OA group (19.05 ng/ml; p< 0.001 for both). Serum adiponectin levels were significantly lower in the MetS-OA group than those in controls (8.09 vs. 10.07 μg/ml, respectively; p= 0.001). The synovium and IPFP in the MetS-OA group secreted more leptin and less adiponectin than those in the non-MetS-OA group (Leptin: 5.32 vs. 1.28 in synovium, respectively; p= 0.028; 6.44 vs. 0.88 in IPFP, respectively; p= 0.017. Adiponectin: 1.12 vs. 0.12 in synovium, respectively; p= 0.042; 1.07 vs. 0.09 in IPFP, respectively; p= 0.027). Resistin expression levels in the serum, SF, and articular tissues were similar among the groups. Conclusions: Expressions of adipokines were different in the synovium and IPFP of OA patients with and without MetS.

Solid-state laser lighting (SSL) fabricated by integrating laser diode with phosphor is a new development to achieve high luminance. Because of the high temperature caused by the laser, the phosphor-conversion apparatus is demanded to possess excellent thermal properties. In this paper, we utilized spark plasma sintering (SPS) to prepare the Al2O3-YAG:Ce phosphor ceramics with outstanding performances. Due to the high thermal conductivity and high transmittance, a high saturation input power (32 W/mm2) can be achieved for the sample with the lowest porosity. The correlated color temperature (CCT) and color rendering index (CRI) of composite ceramics with the lowest porosity are stable as the input power increases from 0.7 W/mm2 to 30.8 W/mm2. Nevertheless, the sample with the highest porosity shows the highest luminescence efficiency (305 lm/W) and luminous emittances (1796 lm/mm2), which can be ascribed to the scattering of the pore.

The mechanisms by which breast cancers progress from relatively indolent ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) are not well understood. However, this process is critical to the acquisition of metastatic potential. MAPK-interacting serine/threonine-protein kinase 1 (MNK1) signaling can promote cell invasion. NODAL, a morphogen essential for embryogenic patterning, is often reexpressed in breast cancer. Here we describe a MNK1/NODAL signaling axis that promotes DCIS progression to IDC. We generated MNK1 knockout (KO) or constitutively active MNK1 (caMNK1)-expressing human MCF-10A–derived DCIS cell lines, which were orthotopically injected into the mammary glands of mice. Loss of MNK1 repressed NODAL expression, inhibited DCIS to IDC conversion, and decreased tumor relapse and metastasis. Conversely, caMNK1 induced NODAL expression and promoted IDC. The MNK1/NODAL axis promoted cancer stem cell properties and invasion in vitro. The MNK1/2 inhibitor SEL201 blocked DCIS progression to invasive disease in vivo. In clinical samples, IDC and DCIS with microinvasion expressed higher levels of phospho-MNK1 and NODAL versus low-grade (invasion-free) DCIS. Cumulatively, our data support further development of MNK1 inhibitors as therapeutics for preventing invasive disease. Significance: These findings provide new mechanistic insight into progression of ductal carcinoma and support clinical application of MNK1 inhibitors to delay progression of indolent ductal carcinoma in situ to invasive ductal carcinoma.

The concomitant risk of physical inactivity and sedentary lifestyle development causing various non-communicable diseases is recognized worldwide. Therefore, development of strategies to form a concrete public health policy overcoming this problem is most important. This study observed the distribution and changes of Body Mass Index (BMI) over six years among boys and girls. Data on children height and weight and their BMI were collected. A total of 5369 (3368 male and 2001 female) children were recruited from 10 schools in Macao. The children were 6 years old in 2008 and turned 11 in 2013. Statistical analyses involved descriptive statistics, t-test, and a Chi-squared test. The findings indicated greater BMI among males than females across all age at the 0.05 level of significance, and the ages of 8 and 9 seemed to be a sensitive period for an increase in overweight and obesity. The results indicate the need to have focused strategies and structured interventions for males at the critical ages from 8 to 9 years.

Melanoma, which has a high metastatic capacity and death rate, is a common skin cancer in Western countries. The purpose of this study was to address whether Juniperus communis (JCo) extract is effective in the suppression of melanoma and to elucidate the anticancer mechanisms involved in vitro and in vivo. The antitumor capacities of JCo extract on tumor suppression and toxicity were evaluated and the results demonstrated that the tumor burden was reduced via mediation of cell cycle, reduction of autocrine signaling, and induction of apoptosis. Moreover, JCo extract significantly prolonged the survival rate of the test subjects with only low pathological and physiological toxicity. Additionally, JCo extract also reduced cancer stem cell-related angiogenic and metastatic proteins in the process of tumor elimination. Based on these results, this study suggests that JCo extract suppresses tumor growth and induces apoptosis, and JCo extract may be useful for the prevention of melanoma tumorigenesis.

Nanoparticle-based combination therapy has been reported as one important treatment strategy to improve the therapeutic efficacy in cancer therapy. However, the traditional co-delivery method often suffers from serious coordination issues that fail to account for the differences in the action sites of each of the drugs, greatly counteracting the synergistic effects of combination agents. Herein, we report a pH-reduction dual responsive drug delivery system for the programmable release of combretastatin A-4 (CA4) and cis-platinum (CDDP). According to their spatial and temporal needs, such nanocarriers could firstly release CA4 in the perivascular sites by responding to the acidic microenvironment of the tumor, then further diffuse throughout the tumor and release CDDP upon redox when being taken-up by the cancer cells. With the help of such spatiotemporal release properties, CA4 and CDDP can target the endothelial cells of tumor vessels and the cancer cells in succession, giving rise to temporal and spatial synergisms. On one hand, the first released CA4 provided a complementary effect for improving tumor accumulation of nanocarriers and the delivery effect of CDDP. On the other hand, CA4 and CDDP respectively targeted their action sites, overall maximizing the therapeutic effect. More importantly, such spatiotemporal drug delivery ability is accomplished by the pH-reduction dual responsive design of the nanocarriers, and thus could also serve as a universal approach for programmable release of other combination agents to improve their synergistic effect in cancer therapy.

ObjectiveAltered metabolites are important for the tumourigenicity of hepatocellular carcinoma (HCC). We performed integrative metabolomics analysis of the metabolites changes in portal venous blood and in comparison with the metabolites changes in liver tissues and stool samples of HCC patients and healthy liver donors.DesignSerum (portal and central vein), liver tissue (HCC tumour and adjacent non-tumour, normal liver) and stool samples were collected from 102 subjects (52 HCC patients and 50 healthy controls) in the discovery cohort; and 100 subjects (50 HCC patients and 50 healthy controls) in an independent validation cohort. Untargeted metabolomic profiling was performed using high-performance liquid chromatography-mass spectrometry. The function of candidate metabolites was validated in hepatocyte cell lines.ResultsDetailed metabolomic evaluation showed distinct clusters of metabolites in serum, liver tissue and stool samples from patients with HCC and control individuals (pConclusionsThe integrative metabolome analysis of serum, tissue and stool metabolites revealed unreported metabolic alterations in HCC patients. In portal vein, we identified elevated and depleted metabolites signifying that they might play a role in HCC development.

IntroductionThe treatment with shikonin (SKN) suppresses the expression of miR-106 and miR-34a. Furthermore, SIRT1 and MCL1 are targets of miR-34a and miR-106, respectively. In this study, we treated an animal model of ALF with high dose (1.0 mg/kg) and low dose (0.5 mg/kg) of SKN to investigate its effect on liver functions and signaling pathways of SKN/miR-106/MCL1 and SKN/miR-34a/SIRT1/TP53.Material and methodsALF animal model was established and the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed to evaluate the effects of different doses of SKN. TUNNEL was performed to assess hepatocyte apoptosis. Luciferase assay, RT-qPCR and Western blot analysis were performed to measure the relationship between miR-106, miR-34a, SIRT1 and MCL1.ResultsIn the ALF mice models, the administration of SKN decreased the levels of ALT and AST in a dose-dependent manner, along with a significantly decreased number of apoptotic hepatocytes. And SKN may protect liver during ALF via reducing the level of inflammation. Luciferase assay showed that the co-transfection of wild-type MCL1/SIRT1 and miR-106/miR-34a significantly decreased the luciferase activity of LO2 cells, thus indicating that MCL1 and SIRT1 are identified as targets of miR-106 and miR-34a, respectively, while SIRT1 could act as a regulator of TP53. Moreover, the expression of miR-106, miR-34a and TP53 was decreased over an increasing concentration of SKN, along with the increasing mRNA and protein levels of MCL1 and SIRT1.ConclusionsIn this study, we showed that SKN alleviated ALF in a dose-dependent manner via regulating the signaling pathways of SKN/miR-106/MCL1 and SKN/miR-34a/SIRT1/TP53.

Multicolor labeling of biological samples with large volume is required for omic-level of study such as the construction of nervous system connectome. Among the various imaging method, two photon microscope has multiple advantages over traditional single photon microscope for higher resolution and could image large 3D volumes of tissue samples with superior imaging depth. However, the growing number of fluorophores for labeling underlines the urgent need for an ultrafast laser source with the capability of providing simultaneous plural excitation wavelengths for multiple fluorophores. Here, we propose and demonstrate a single-laser-based four-wavelength excitation source for two-photon fluorescence microscopy. Using a sub-100 fs 1,070-nm Yb:fiber laser to pump an ultrashort nonlinear photonic crystal fiber in the low negative dispersion region, we introduced efficient self-phase modulation and acquired a blue-shifted spectrum dual-peaked at 812 and 960 nm with 28.5% wavelength conversion efficiency. By compressing the blue-shift near-IR spectrum to 33 fs to ensure the temporal overlap of the 812 and 960 nm peaks, the so-called sum frequency effect created the third virtual excitation wavelength effectively at 886 nm. Combined with the 1,070 nm laser source as the fourth excitation wavelength, the all-fiber-format four-wavelength excitation source enabled simultaneous four-color two-photon imaging in Brainbow AAV-labeled (TagBFP, mTFP, EYFP, and mCherry) brain samples. With an increased number of excitation wavelengths and improved excitation efficiency than typical commercial femtosecond lasers, our compact four-wavelength excitation approach can provide a versatile, efficient, and easily accessible solution for multiple-color two-photon fluorescence imaging in the field of neuroscience, biomolecular probing, and clinical applications with at least four spectrally-distinct fluorophores.

Background This study aims to investigate the risk factors of perioperative neurocognitive disorders (PNDs) mainly including postoperative cognitive dysfunction (POCD) in elderly patients with gastrointestinal tumors, and evaluate its predictive value. Methods A total of 222 eligible elderly patients (≥65 years) scheduled for elective gastroenterectomy under general anesthesia were enrolled. The cognitive function assessment was carried out 1 day before surgery and 7 days after surgery. Receiver operating characteristic curve analysis was performed to evaluate the predictive value of risk factors for early POCD. The risk factors for POCD were analyzed using univariate and multivariate logistic regression model. Results Of all the 222 enrolled patients, 91 (41.0%) developed early POCD and 40 (18.0%) were identified as major POCD within 7 days after the surgery. Visual analogue score (VAS, 1st day, resting) ≥4 (OR = 7.618[3.231–17.962], P P = 0.016) were independent risk factors for early POCD. VAS score (1st, resting) ≥4 (OR = 13.823[4.779–39.981], P P = 0.035), blood loss ≥500 ml (OR = 3.317[1.094–10.059], P = 0.034), history of hypertension (OR = 3.046[1.267–7.322], P = 0.013), and neutrophil–lymphocyte ratio (NLR) ≥2 (OR = 3.261[1.020–10.419], P = 0.046) were independent risk factors for major POCD. Receiver operating characteristic curve analysis indicated that VAS score (1st day, resting) was a significant predictor for major POCD with a cut-off value of 2.68 and an area under the curve of 0.860 (95% confidence interval: 0.801–0.920, P Conclusions The risk factors for early POCD after gastroenterectomy included high VAS score (1st day, resting) and alcohol exposure. High VAS score, preoperative WBC levels ≥10 × 10*9/L, blood loss ≥500 ml, NLR ≥2, and history of hypertension were independent risk factors for major POCD. Among them, VAS score was one of the important predictors.

BACKGROUND Nurses who work in hospitals experience a high level of burnout and the relationship between immune variables and burnout syndrome has yet to be elucidated. The aim of the present study was to investigate the effects of job burnout on immune function in female oncology nurses in a tertiary oncology hospital in Guangxi, China. The aspects of the human immune system evaluated were humoral and cellular immunity and complement components 3 (C3) and 4 (C4). MATERIAL AND METHODS We administered the Maslach Burnout Inventory-General Survey (MBI-GS), which includes scales for emotional exhaustion, depersonalization (DP), and personal accomplishment (PA), to measure variables related to immune function in 105 female nurses in a tertiary oncology hospital in Guangxi, China. Levels of humoral immunity and C3 and C4 were detected with immune turbidimetry. Cellular immunity was assessed with indirect immunofluorescence. RESULTS A Spearman rank correlation analysis revealed that levels of C3, C4, and CD4- and CD8-positive T cells were significantly associated with burnout symptoms (P

To evaluate Pneumocystis jirovecii pneumonia (PJP) infection risk in patients with systemic lupus erythematosus (SLE) in Taiwan.We identified 24,367 patients with SLE from the National Health Insurance research database between 1997 and 2012 and compared the PJP incidence rates (IRs) with those in 243,670 age- and sex-matched non-SLE controls. PJP risk in the patients was evaluated using a Cox multivariate proportional hazards model.The SLE patients exhibited a significantly higher PJP risk than the controls, with an IR of 2.63 per 10,000 person-years and IR ratio of 27.65 (95% confidence interval 17.2-45.3; P 0.001). Male sex (hazard ratio [HR] 2.42, P 0.01), end-stage renal disease (ESRD; HR 1.74, P = 0.01), recent use of mycofenolate mofetil (MMF; HR 4.43, P 0.001), intravenous steroid pulse therapy (HR 108.73, P 0.001), and average oral dosage of7.5 mg/day prednisolone or equivalent treatment (HR 4.83, P 0.001) were associated with PJP in SLE, whereas hydroxychloroquine use reduced its risk (HR 0.51, P = 0.01). Of note, cyclophosphamide was not associated with PJP infection in the multivariate Cox proportional hazard model.Patients with SLE have a considerably high PJP risk. Cyclophosphamide does not increase PJP risk. Male sex, ESRD, MMF use, intravenous steroid pulse therapy, and oral prednisolone or equivalent treatment (7.5 mg/day) are risk factors for PJP, whereas hydroxychloroquine use reduces PJP risk.

Background: Herpes zoster-associated pain [i.e., acute herpes zoster neuralgia (AHN) and postherpetic neuralgia (PHN)] has the potential to cause significant patients’ burden and heath resource expenditure. PHN is refractory to the existing treatments, and the consensus is preventing the transition of AHN to PHN is better than treating PHN. Anticonvulsants (e.g., gabapentin, pregabalin) have been recommended as one of the first-line therapies for PHN. In practice, anticonvulsants have also decreased the severity and duration of AHN and reduced the incidence of PHN. Nevertheless, its clinical application to AHN is hampered by inadequate evidence for its efficacy and safety. We performed this protocol for a systematic review to explore the efficacy and safety of anticonvulsants for AHN. Besides, a benefit-risk assessment of anticonvulsants for AHN would be performed to estimate the extent to which these drugs could relieve symptoms and whether the benefits outweigh harms. Methods: The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) was used to prepare our protocol and the results will be reported according to the PRISMA. We will search the China National Knowledge Infrastructure (CNKI), Chinese VIP Information (VIP), Cochrane Library, Embase, and PubMed databases, from inception to August 2019. Furthermore, Clinicaltrials (http://www.clinicaltrials.com) and Chinese Clinical Trial Registry (http://www.chictr.org.cn/abouten.aspx) will also be searched for relevant studies. Selection of eligible articles and data extraction will be independently performed by reviewers. We will record the characteristic information, pain outcomes, incidence of PHN and adverse effects. Data synthesis and other statistical analyses will be conducted using Review Manager Software 5.3 and STATA13.0. Furthermore, risk of bias assessment, meta-regression and subgroup analyses, publication bias assessment, grading of evidence will be performed for included studies. Ethics and dissemination: As this systematic review will be performed based on published data, no ethical approval is needed. The findings will be submitted in peer-reviewed journals for publication. Systematic review registration: PROSPERO CRD42019133449.

Field-programmable gate arrays (FPGAs) are widely used in many fields because of their low power consumption, easy design and good performance. For applications running on FPGAs, security is very important. A lot of researches have been done on the security issue of FPGA implementations, many attacks and countermeasures have been proposed. The dual complementary strategy is a countermeasure designed to thwart side channel attacks. In this paper, we perform Correlation Power Analysis (CPA) against dual complementary AES implemented on the SAKURA-G FPGA board. For dual complementary AES with constant Hamming Weight (HW) value, which is demonstrated to be robust against CPA based on HW model, we successfully recover the secret key using Hamming Distance (HD) and Switching Distance (SD) models with 2,000 power traces. For dual complementary AES with constant HD, 16,000 resp. 10,000 power traces are required to recover the key with HD resp. SD model.

Background Whether using tissue adhesive alone after subcutaneous suture can close the skin incision with safety as well as cosmetic appearance after total hip arthroplasty was not clear. Methods A prospective study was conducted. The same surgical methods were consistent throughout the entire study. After implanting prosthesis, the joint capsule was reconstructed. Fascial and subcutaneous layer were respectively closed by continuous running barbed suture. Patients were randomized allocated to group A with octyl-2-cyanoacrylate tissue adhesive alone, to group B with tissue adhesive after continuous subcuticular suture, or to group C with skin staples. Time of closure, drainage, pain, wound complications, and cosmesis were compared. All data were analyzed statistically. Results There was no significant difference in drainage, Visual Analog Scale score or early wound complications between the three groups. However, there was significant difference in time of closure (P = 0.013). In pairwise comparison, time of closure in groups A and B was significantly longer than those in group C (P = 0.001 and P = 0.023, respectively); time of closure in group A was significantly shorter than those in group B (P = 0.003). Patient and Observer Scar Assessment Scale total scores were not significantly different at 6 weeks and 3 months postoperatively (P = 0.078 and P = 0.284, respectively). Conclusion Tissue adhesive without subcuticular suture was similar with a combination of subcuticular suture and tissue adhesive as well skin staples in terms of safety and cosmetic appearance after total hip arthroplasty.

PROBLEM The chorionic bump is a distinct rare sonographic abnormality. Until now, there is contradictory evidence about if it associates with poor pregnancy outcomes. We performed this retrospective study to provide additional clinical data to investigate the clinical significance of chorionic bump at early stage of pregnancy. METHOD OF STUDY A single-center retrospective study was performed using the sonographic and clinical data of the pregnant women who had antenatal checkup and childbirth at Shanghai First Maternal and Child Health Care Center from December 2018 to December 2019. Sonographic examination was performed by experts at 5-10 weeks' gestation. Maternal age and gestational age matched controls from the same period were selected for analysis. RESULTS We observed 83 chorionic bump cases showing a prevalence of 0.33%. We found previous intrauterine operations and/or adverse maternal history posed a risk of having chorionic bump. In our cohort, chorionic bump associates with poor pregnancy outcomes. Poor pregnancy outcomes were more frequently found in the patients whose lesions were detected early (

PurposeBreast cancer diagnosed within 10 years following childbirth is defined as postpartum breast cancer (PPBC) and is highly metastatic. Interactions between immune cells and other stromal cells within the involuting mammary gland are fundamental in facilitating an aggressive tumor phenotype. The MNK1/2-eIF4E axis promotes the translation of pro-metastatic mRNAs in tumor cells, but its role in modulating the function of non-tumor cells in the PPBC microenvironment, and in particular its activity in human PPBC, has not been explored.Experimental designWe used a combination of in vivo PPBC models and in vitro assays to study the effects of phospho-eIF4E deficiency on the pro-tumor function of select cells of the TME. Furthermore, we employed Imaging Mass Cytometry on PPBC and non-PPBC patient samples, to chart the expression of the MNK1/2-eIF4E axis components in the TME.ResultsHere, we show that phospho-eIF4E deficient (eIF4ES209A) PPBC mice are protected against lung metastasis and reveal differences in the lung immune microenvironment of the WT and eIF4ES209A mice. Moreover, we show that the expression of fibroblast-derived IL-33, an alarmin known to induce invasion, was repressed upon MNK1/2-eIF4E axis inhibition. Imaging Mass Cytometry results indicated that human PPBC contain phospho-eIF4E high-expressing tumor cells and CD8+ T cells displaying an activated dysfunctional phenotype. Finally, we block lung metastasis in PPBC mice, using combined MNK1/2 inhibition and anti-PD-1 therapy.ConclusionsThese findings implicate the involvement of the MNK1/2-eIF4E axis during PPBC metastasis and suggest a promising immunomodulatory route to enhance the efficacy of immunotherapy by blocking phospho-eIF4E.Translational relevancePostpartum breast cancer (PPBC) is highly aggressive. It is hypothesized that involution-induced changes in the postpartum breast microenvironment, which include an influx of inflammatory immune cells and activation of resident fibroblasts, facilitate the invasiveness of an existing neoplasm. We used imaging mass cytometry to do an in-depth profiling of the MNK1-eIF4E axis in the TME of a unique cohort of PPBC and non-PPBC patients. We observed patterns of phospho-eIF4E in non-tumor cells that were specific to the TME of PPBC. We also noted that the CD8+ T cells present in PPBC express an activated dysfunctional phenotype characterized by the co-expression of HLA-DR and PD-1. This study represents a first look at the expression of the MNK1-eIF4E axis in the stromal cells of metastatic breast cancer and has therapeutic implications as we show, in an animal model of PPBC, that MNK1/2 inhibition can be used to sensitize tumors to anti-PD1 immunotherapy.

The oral cancer incidence rate is slowly increasing and is now the fifth leading cause of cancer-related death due to its high metastasis and recurrence rate. Juniperus communis is used as a traditional Chinese medicine and has been proven to have anti-cancer activity against neuroblastomas. In the present study, we further investigated the anti-cancer mechanisms of J. communis extract (JCo) on oral cancer and evaluated the synergistic effects of JCo combined with 5-fluorouracil (5-FU). We found that JCo inhibited oral cancer cell growth, and that JCo might be less cytotoxic to normal cells than to cancer cells. After JCo treatment, cell cycle arrest was observed at the G0/G1 phase through modulation of p53/p21 and Rb signaling. JCo also caused an increase in the sub-G1 phase and cell apoptosis via the intrinsic and extrinsic apoptosis pathways. JCo combined with 5-FU presented a synergistic effect to reduce cell viability. In conclusion, JCo inhibited oral cancer cell growth by inducing cell cycle arrest and activating cell apoptosis, and JCo significantly synergized with 5-FU. JCo might have the potential to be an adjuvant and a new therapeutic drug for oral cancer treatment.

Fundus photography has been widely used for inspecting eye disorders by ophthalmologists or computer algorithms. Biomarkers related to retinal vessels plays an essential role to detect early diabetes. To quantify vascular biomarkers or the corresponding changes, an accurate artery and vein classification is necessary. In this work, we propose a new framework to boost local vessel classification with a global vascular network model using graph convolution. We compare our proposed method with two traditional state-of-the-art methods on a testing dataset of 750 images from the Maastricht Study. After incorporating global information, our model achieves the best accuracy of 86.45% compared to 85.5% from convolutional neural networks (CNN) and 82.9% from handcrafted pixel feature classification (HPFC). Our model also obtains the best area under receiver operating characteristic curve (AUC) of 0.95, compared to 0.93 from CNN and 0.90 from HPFC. The new classification framework has the advantage of easy deployment on top of local classification features. It corrects the local classification error by minimizing global classification error and it brings free additional classification performance.

The CTR (Click-Through Rate) prediction plays a central role in the domain of computational advertising and recommender systems. There exists several kinds of methods proposed in this field, such as Logistic Regression (LR), Factorization Machines (FM) and deep learning based methods like Wide&Deep, Neural Factorization Machines (NFM) and DeepFM. However, such approaches generally use the vector-product of each pair of features, which have ignored the different semantic spaces of the feature interactions. In this paper, we propose a novel Tensor-based Feature interaction Network (TFNet) model, which introduces an operating tensor to elaborate feature interactions via multi-slice matrices in multiple semantic spaces. Extensive offline and online experiments show that TFNet: 1) outperforms the competitive compared methods on the typical Criteo and Avazu datasets; 2) achieves large improvement of revenue and click rate in online A/B tests in the largest Chinese App recommender system, Tencent MyApp., To appear at SIGIR 2020

Background Endoplasmic reticulum (ER) perturbations are novel subcellular effectors involved in the ischaemia-reperfusion injury. As an ER stress-inducible protein, mesencephalic astrocyte-derived neurotrophic factor (MANF) has been proven to be increased during ischaemic brain injury. However, the role of MANF in liver ischaemia reperfusion (I/R) injury has not yet been studied. Methods To investigate the role of MANF in the process of liver ischaemia-reperfusion, Hepatocyte-specific MANF knockout (MANFhep-/- ) mice and their wild-type (WT) littermates were used in our research. Mice partial (70%) warm hepatic I/R model was established by vascular occlusion. We detected the serum levels of MANF in both liver transplant patients and WT mice before and after liver I/R injury. Recombinant human MANF (rhMANF) was injected into the tail vein before 1 hour occlusion. AST, ALT and Suzuki score were used to evaluate the extent of I/R injury. OGD/R test was performed on primary hepatocytes to simulate IRI in vitro. RNA sequence and RT-PCR were used to detect the cellular signal pathway activation while MANF knockout. Results We found that MANF expression and secretion are dramatically up-regulated during hepatic I/R. Hepatocyte-specific MANF knockout aggravates the I/R injury through the over-activated ER stress. The systemic administration of rhMANF before ischaemia has the potential to ameliorate I/R-triggered UPR and liver injury. Further study showed that MANF deficiency activated ATF4/CHOP and JNK/c-JUN/CHOP pathways, and rhMANF inhibited the activation of the two proapoptotic pathways caused by MANF deletion. Conclusion Collectively, our study unravels a previously unknown relationship among MANF, UPR and hepatic I/R injury.

Fan Huang,1,* Mingwang Qiu,2,* Siyi Zhao,1,* Lin Dai,2 Yanpeng Xu,2 Yunying Yang,2 Liming Lu,2 Rusong Guo,1,3 Qiang Tian,1,3 Zhiyong Fan,1,3 Shan Wu1,3 1The Second School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, People’s Republic of China; 2Clinical Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, People’s Republic of China; 3Guangdong Province Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiyong Fan; Shan Wu Guangdong Province Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; Guangdong Province Hospital of Chinese Medicine, Guangzhou 510120, Guangdong, People’s Republic of China Tel +86 188 9863 2932Email fzystrong@163.com; wushan6866@sina.comObjective: To evaluate systematic reviews (SRs) of acupuncture for low back pain (LBP) in terms of characteristics, reporting and methodological quality using a Veritas plot and to explore factors that may be associated with methodological quality and reporting quality.Study Design and Setting: We searched 8 electronic bibliographic databases to find all SRs, and we evaluated the SRs’ quality in 6 dimensions, including publication year, design type, homogeneity, risk of publication bias, methodological quality by Assessment of Multiple Systematic Reviews (AMSTAR) 2 and reporting quality by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Excel 2010 and Adobe Illustrator CC were used to draw and optimize Veritas plots. Exploratory analysis was done using SPSS software version 23.0 to explore factors related to AMSTAR-2 and PRISMA scores. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) evidence quality evaluation tool was used to grade all the outcome indicators in the included literature.Results: We included 19 SRs in the analysis. Literature quality rank scores ranged from 9.67 to 17.00, with an average score of 13.18 ± 2.35. The average score of AMSTAR-2 was 7.47, and the average score of PRISMA was 18.47. Overall, the main issues were research strategies, inclusion and exclusion criteria, publication bias, and registration in PROSPERO. The results of exploratory analysis showed that duplication of literature selected and appropriate tools to assess the risk of bias were related to the AMSTAR-2 score, and the summary of evidence was related to the PRISMA score. The GRADE quality evaluation results showed mainly low quality.Conclusion: The quality of SRs on acupuncture for low back pain should be improved, mainly by strengthening the methodological quality and reporting quality. The Veritas plot is an effective graphical evaluation method that is worth popularizing.Keywords: reporting quality, methodological quality, AMSTAR-2, low back pain, PRISMA, systematic review

Background To investigate the resilience of non-local medical workers sent to support local medical workers in treating the outbreak of 2019 novel coronavirus disease (COVID-19). Methods In February 2020, non-local medical workers who had been sent to Wuhan as support staff to respond to the COVID-19 outbreak were asked to complete an online survey composed of the Connor Davidson Resilience Scale (CD-RISC), Hospital Anxiety Depression Scale (HADS) and Simplified Coping Style Questionnaire (SCSQ). Results Survey responses from 114 non-local medical workers were analyzed. CD-RISC scores were high (67.03 ± 13.22). The resilience level was highest for physicians (73.48 ± 11.49), followed by support staff, including health care assistants, technicians (67.78 ± 12.43) and nurses (64.86 ± 13.46). Respondents differed significantly in the levels of education, training/support provided by the respondent’s permanent hospital (where he or she normally works), and in their feelings of being adequately prepared and confident to complete tasks (P r = −.498, P r = −.471, P r = .733, P β = 1.314, p β = −.806, p β = − 1.091, p β = 3.510, p Conclusion Our data show that active coping, depression, anxiety, and training/support provided by the respondent’s permanent hospital are associated with resilience. Managers of medical staff should use these data to develop psychosocial interventions aimed at reinforcing the resilience of medical workers during highly stressful and prolonged medical emergencies, as seen during the COVID-19 outbreak.

Geometric and topological features of corneal nerve fibers in confocal microscopy images are important indicators for the diagnosis of common diseases such as diabetic neuropathy. Quantitative analysis of these important biomarkers requires an accurate segmentation of the nerve fiber network. Currently, most of the analysis are performed based on manual annotations of the nerve fiber segments, while a fully automatic corneal nerve fiber extraction and analysis framework is still needed. In this paper, we establish a fully convolutional network method to precisely enhance and segment corneal nerve fibers in microscopy images. Based on the segmentation results, automatic tortuosity measurement and branching detection modules are established to extract valuable geometric and topological biomarkers. The proposed segmentation method is validated on a dataset with 142 images. The experimental results show that our deep learning-based framework outperforms state-of-the-art segmentation approaches. The biomarker extraction methods are validated on two different datasets, demonstrating high effectiveness and reliability of the proposed methods.

Changes in expression patterns of serum carcinoembryonic antigen at initial diagnosis (CEAIn) and disease progression (CEAPd) in lung cancer patients under EGFR-tyrosine kinase inhibitors (TKI) treatment may reflect different tumor progression profiles. Of the 1736 lung cancer patients identified from the cancer registry group between 2011 to 2016, we selected 517 patients with advanced stage adenocarcinoma, data on EGFR mutation status and CEAIn, among whom were 288 patients with data on CEAPd, eligible for inclusion in the correlation analysis of clinical characteristics and survival. Multivariable analysis revealed that CEAIn expression was associated with poor progression-free survival in patients harboring mutant EGFR. Moreover, CEAIn and CEAPd were associated with the good and poor post-progression survival, respectively, in the EGFR-mutant group. Cell line experiments revealed that CEA expression and cancer dissemination can be affected by EGFR-TKI selection. EGFR-mutant patients, exhibiting high CEAIn (≥5 ng/mL) and low CEAPd (In and CEAPd in patients under EGFR-TKI treatment, and CEAIn and CEAPd are associated with distinct cancer progression profiles.

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Leakage assessment is the most common approach applied for assessing side-channel information leakage and validating the effectiveness of side-channel countermeasures. Established evaluation approaches are usually based on Test Vector Leakage Assessment (TVLA) that deployed in a divide and conquer flow with offline computations, which causes two apparent shortcomings in required memory and time. In this paper, a lightweight framework of online leakage assessment is proposed. The problems were analyzed and the evaluation approach was further validated with a Field Programmable Gate Array (FPGA). The experimental results show that it can implement online processing on newly collected data, and instantly stop to give the result when detecting credible leakage. The online leakage assessment can significantly economize on memory and time. It has good performance when there is limited memory or real-time evaluations are needed.

Entity Resolution (ER) identifies records that refer to the same real-world entity. Deep learning approaches improved the generalization ability of entity matching models, but hardly overcame the impact of noisy or incomplete data sources. In real scenes, an entity usually consists of multiple semantic facets, called aspects. In this paper, we focus on entity augmentation, namely retrieving the values of missing aspects. The relationship between aspects is naturally suitable to be represented by a knowledge graph, where entity augmentation can be modeled as a link prediction problem. Our paper proposes a novel graph-based approach to solve entity augmentation. Specifically, we apply a dedicated random walk algorithm, which uses node types to limit the traversal length, and encodes graph structure into low-dimensional embeddings. Thus, the missing aspects could be retrieved by a link prediction model. Furthermore, the augmented aspects with fixed orders are served as the input of a deep Siamese BiLSTM network for entity matching. We compared our method with state-of-the-art methods through extensive experiments on downstream ER tasks. According to the experiment results, our model outperforms other methods on evaluation metrics (accuracy, precision, recall, and f1-score) to a large extent, which demonstrates the effectiveness of our method.

Background: Cigarette smoking increases the risk of diabetes. The gut microbiota plays a crucial role in the pathogenesis of diabetes. However, the overall effects that active smoking has on the digestive tract microbiome are unclear. Smoking-induced alterations in the digestive tract microbiome and hyperglycemia have not been investigated simultaneously. Methods: We develop a rat model of active smoking and comprehensively characterize the effects of active smoking on the microbiota within multiple regions along the digestive tract. Blood glucose and some metabolic factors levels, the microbial diversity and composition, bacterial network correlations and predictive functional profiles were compared between the control group and active smoking group. Findings: We found that active smoking induced hyperglycemia and dramatic reductions in serum insulin and leptin levels. Active smoking did not remarkably alter the alpha diversity in each region, but induced significant difference in the beta diversity and community structure in the gastrointestinal tract. Our results demonstrated that active smoking resulted in a reduced abundance of some butyrate-producing bacteria (i.e. Clostridium) and increased abundance of sulphate-reducing bacteria (i.e. Desulfovibrio and Bilophila) in the stomach and cecum, and enrichment of opportunistic pathogens (i.e. Staphylococcus) in the oral cavity, cecum and colon. Functional prediction suggested that nutritional metabolism function could be impaired and antioxidant activity may be triggered. Interpretation: These results suggest that investigations of the digestive tract microbiome might be useful for further pathogenesis exploration and treatment improvement of smoking-related diseases. Funding Statement: This work was supported by the National Natural Scientific Foundation of China (81870767 & 81570978), the Key Project of Science and Technology Department of Jiangsu Province (BL2014018), the Project of Jiangsu Provincial Medical Youth Talent (QNRC2016118), the Natural Science Foundation of Jiangsu Province (BK20190134), the Preventive Medicine Project of Jiangsu Province (Y2015004), and the Nanjing Medical Science and Technique Development Foundation (ZKX17033 & YKK16162). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All experimental procedures were approved by the local Animal Care and Ethics Committee [IRB Approval Number: 2015NL-001 (ks)].