Feasibility analysis of China's medical insurance coverage of assisted reproductive technology.

There are millions of patients experiencing infertility in China, but assisted reproductive technology (ART) is performed at the patient's expense and is difficult to afford. With the sharp decline in China's birth rate, there is a growing controversy over the inclusion of ART in medical insurance (MI). This study aims to explore the feasibility of ART coverage by MI for the first time. We obtained basic data such as the prevalence of infertility, the cost of ART, and the success rate in China with the method of meta-analysis and consulting the government bulletin. Then, we calculated the number of infertile couples in China and the total financial expenditure of MI covering ART. Finally, we discussed the feasibility of coverage, and analyzed the population growth and economic benefits after coverage. According to our research results, it was estimated that there were 4.102-11.792 million infertile couples in China, with an annual increase of 1.189-1.867 million. If MI covered ART, the fund would pay 72.313-207.878 billion yuan, accounting for 2-6% of the current fund balance, and the subsequent annual payment would be 20.961-32.913 billion yuan, accounting for 4-7% of the annual fund balance. This was assuming that all infertile couples would undergo ART, and the actual cost would be lower. The financial input‒output ratio would be 13.022. Benefiting from the inclusion of ART in MI coverage, there would be 3.348-9.624 million new live infants, and 8-13% newborns would be born every year thereafter, which means that by 2050, 37-65 million people would be born. Due to its affordable cost, high cost-effectiveness and favourable population growth, it may be feasible to include ART in MI.

Optimizing broadband antireflection with Au micropatterns: a combined FDTD simulation and two-beam LIL approach.

Broadband antireflection (AR) is highly significant in a wide range of optical applications, and using a gold (Au) micropattern presents a viable method for controlling the behavior of light propagation. This study investigates a novel, to the best of our knowledge, methodology to achieve broadband AR properties in Au micropatterns. It employed the three-dimensional finite-difference time-domain (FDTD) method to simulate and optimize the design of micropatterns. In contrast, the fabrication of Au micropatterns was carried out using two-beam laser interference lithography (LIL). The fabricated Au micropatterns were characterized by a scanning electron microscope (SEM) and spectroscope to validate their antireflection and transmission properties and evaluate their performance at various wavelengths. The optimized Au micropatterns had a high transmittance rating of 96.2%. In addition, the device exhibits a broad-spectrum antireflective property, covering wavelengths ranging from 400 to 1100 nm. The simulation data and experimentally derived results show comparable patterns. These structures can potentially be employed in many optical devices, such as solar cells and photodetectors, whereby achieving optimal device performance reduced reflection and enhanced light absorption.

Superhydrophobic Antifrosting 7075 Aluminum Alloy Surface with Stable Cassie-Baxter State Fabricated through Direct Laser Interference Lithography and Hydrothermal Treatment.

Frost formation and accumulation can have catastrophic effects on a wide range of industrial activities. Hence, a dual-scale surface with a stable Cassie-Baxter state is developed to mitigate the frosting problem by utilizing direct laser interference lithography assisted with hydrothermal treatment. The high Laplace pressure tolerance under the evaporation stimulus and prolonged Cassie-Baxter state maintenance under the condensation stimulus demonstrate the stable Cassie-Baxter state. The dual-scale surface exhibits a lengthy frost-delaying time of up to 5277 s at -7 °C due to the stable Cassie-Baxter state. The self-removal of frost is achieved by promoting the mobility of frost melts driven by the released interfacial energy. In addition, the dense flocculent frost layer is observed on the single-scale micro surface, whereas the sparse pearl-shaped frost layer with many voids is obtained on the dual-scale surface. This work will aid in understanding the frosting process on various-scale superhydrophobic surfaces and in the design of antifrosting surfaces.

Long-term outcome of children with acute promyelocytic leukemia: a randomized study of oral versus intravenous arsenic by SCCLG-APL group.

Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.

Anti-Glioma Effects of Ligustilide or n-Butylphthalide on Their Own and the Synergistic Effects with Temozolomide via PI3K/Akt Signaling Pathway.

Background: Ligustilide (LIG) and n-butylphthalide (NBP) have neuroprotective effects in cerebral ischemia; however, their roles in gliomas are not well-known.This study aimed to explore the anti-glioma effects of LIG and NBP individually and the synergistic effects of temozolomide (TMZ) via the PI3K/Akt Signaling Pathway. Materials and Methods: Cytotoxicity of LIG and NBP alone and in combination with TMZ in U251 cells was determined using the CCk-8. The effect of compounds alone or in combination on cell migration was detected using the wound healing assay, and the invasion was evaluated by transwell assays, respectively. Cell apoptosis was quantified by flow cytometry and the changed expressions of proteins were detected by Western blotting. Results: The results showed that LIG and NBP significantly inhibited the growth of U251 cells at concentrations of 4-10 µg/mL and 1.5-6 µg/mL in a dose-dependent manner (p<0.05, p<0.01). The combination of 20 µg/mL TMZ with LIG in the concentration range of 4-10 µg/mL or with NBP of 0.5-6 µg/mlachieved synergistic effect towardsU251 cells. LIG and NBP, alone or in combination with TMZ, markedly inhibited cell invasion (p< 0.001) and enhanced apoptosis (p< 0.05). The combination of TMZ with LIG or NBP markedly inhibited cell migration (p< 0.001). Western blot analysis showed that LIG, NBP, and TMZ, alone and in combination, significantly decreased the expression of Bcl-2, p-PI3K, and p-Akt, and increased the expression of Bax. Conclusion: Both LIG and NBP exert anti-glioma effects on their own through the PI3K/Akt pathway and enhance TMZ-mediated anti-glioma efficiency via the same pathway.

Trim21 depletion alleviates bone loss in osteoporosis via activation of YAP1/ß-catenin signaling.

Despite the diverse roles of tripartite motif (Trim)-containing proteins in the regulation of autophagy, the innate immune response, and cell differentiation, their roles in skeletal diseases are largely unknown. We recently demonstrated that Trim21 plays a crucial role in regulating osteoblast (OB) differentiation in osteosarcoma. However, how Trim21 contributes to skeletal degenerative disorders, including osteoporosis, remains unknown. First, human and mouse bone specimens were evaluated, and the results showed that Trim21 expression was significantly elevated in bone tissues obtained from osteoporosis patients. Next, we found that global knockout of the Trim21 gene (KO, Trim21-/-) resulted in higher bone mass compared to that of the control littermates. We further demonstrated that loss of Trim21 promoted bone formation by enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and elevating the activity of OBs; moreover, Trim21 depletion suppressed osteoclast (OC) formation of RAW264.7 cells. In addition, the differentiation of OCs from bone marrow-derived macrophages (BMMs) isolated from Trim21-/- and Ctsk-cre; Trim21f/f mice was largely compromised compared to that of the littermate control mice. Mechanistically, YAP1/ß-catenin signaling was identified and demonstrated to be required for the Trim21-mediated osteogenic differentiation of BMSCs. More importantly, the loss of Trim21 prevented ovariectomy (OVX)- and lipopolysaccharide (LPS)-induced bone loss in vivo by orchestrating the coupling of OBs and OCs through YAP1 signaling. Our current study demonstrated that Trim21 is crucial for regulating OB-mediated bone formation and OC-mediated bone resorption, thereby providing a basis for exploring Trim21 as a novel dual-targeting approach for treating osteoporosis and pathological bone loss.

Association between living environmental quality and risk of arthritis in middle-aged and older adults: a national study in China.

Background: The association between combined environmental factors and the risk of arthritis is still scarcely studied. The present study performed cross-sectional and cohort studies to explore the association between risk score of living environment quality and the risk of arthritis in middle-aged and older adults in China. Methods: The study was based on China Health and Retirement Longitudinal Study (CHARLS), and it recruited 17,218 participants in the cross-sectional study and 11,242 participants in the seven-year follow-up study. The living environment quality was measured by household fuel types, household water sources, room temperature, residence types, and ambient concentration of PM2.5. Logistic regression and Cox proportional hazard regression models were utilized to examine the association between the living environment quality and the risk of arthritis. Competing risk models and stratified analyses were applied to further verify our results. Results: Compared with individuals in the suitable environment group, people who lived in moderate (OR:1.28, 95%CI: 1.14-1.43) and unfavorable environments (OR:1.49, 95%CI:1.31-1.70) showed higher risks of arthritis when considering the multiple living environmental factors (P for trend <0.001) in the cross-sectional analysis. In the follow-up study, similar results (P for trend = 0.021), moderate environment group (HR:1.26, 95%CI:1.01-1.56) and unfavorable environment group (HR: 1.36, 95%CI: 1.07-1.74), were founded. Conclusion: Inferior living environment might promote the development of arthritis. It is necessary for the public, especially old people, to improve the living environment, which may be the key to the primary prevention of arthritis.

The impact of fasting plasma glucose variability on osteoporotic fractures.

Purpose: To investigate the impact of FPG variability on osteoporotic fractures in the entire community population. Methods: All participants were from the Kailuan Study. Participants completed three consecutive surveys from 2006-2007, 2008-2009, and 2010-2011. We excluded individuals with an osteoporotic fracture in or prior to the index year and those without complete FPG records at the first 3 examinations. All participants were followed from the date of the 3rd examination to the first occurrence of an endpoint event or December 31, 2021. According to the SD of FPG levels, the included subjects were divided into three groups. A Cox proportional hazards model was performed to further analyze the effect of different FPG-SD groups on the risk of osteoporotic fractures. Results: Ultimately, the study population included 57295 participants. During a median follow-up time of 11.00 years, we documented 772 new osteoporotic fracture cases. When evaluating the FPG-SD level as a categorical variable, the HRs for osteoporotic fractures were 1.07 (95% CI: 0.89-1.29) for T2 and 1.32 (95% CI: 1.10-1.60) for T3 when compared with T1. We found that increased FPG variability was associated with a greater risk of osteoporotic fractures in people with diabetes than in those without diabetes (47% vs. 32%). Conclusion: Increased FPG variability was an independent predictor of incident osteoporotic fracture, especially in individuals older than 50 years old, nonobese individuals, diabetes patients, and individuals with positive FPG-SD variability.

Laser Interference Lithography-A Method for the Fabrication of Controlled Periodic Structures.

A microstructure determines macro functionality. A controlled periodic structure gives the surface specific functions such as controlled structural color, wettability, anti-icing/frosting, friction reduction, and hardness enhancement. Currently, there are a variety of controllable periodic structures that can be produced. Laser interference lithography (LIL) is a technique that allows for the simple, flexible, and rapid fabrication of high-resolution periodic structures over large areas without the use of masks. Different interference conditions can produce a wide range of light fields. When an LIL system is used to expose the substrate, a variety of periodic textured structures, such as periodic nanoparticles, dot arrays, hole arrays, and stripes, can be produced. The LIL technique can be used not only on flat substrates, but also on curved or partially curved substrates, taking advantage of the large depth of focus. This paper reviews the principles of LIL and discusses how the parameters, such as spatial angle, angle of incidence, wavelength, and polarization state, affect the interference light field. Applications of LIL for functional surface fabrication, such as anti-reflection, controlled structural color, surface-enhanced Raman scattering (SERS), friction reduction, superhydrophobicity, and biocellular modulation, are also presented. Finally, we present some of the challenges and problems in LIL and its applications.

Differentiation syndrome and coagulation disorder - comparison between treatment with oral and intravenous arsenics in pediatric acute promyelocytic leukemia.

Realgar-Indigo naturalis formula (RIF), with A4S4 as a major ingredient, is an oral arsenic used in China to treat pediatric acute promyelocytic leukemia (APL). The efficacy of RIF is similar to that of arsenic trioxide (ATO). However, the effects of these two arsenicals on differentiation syndrome (DS) and coagulation disorders, the two main life-threatening events in children with APL, remain unclear. We retrospectively analyzed 68 consecutive children with APL from South China Children Leukemia Group-APL (SCCLG-APL) study. Patients received all-trans retinoic acid (ATRA) on day 1 of induction therapy. ATO 0.16 mg/kg day or RIF 135 mg/kg·day was administrated on day 5, while mitoxantrone was administered on day 3 (non-high-risk) or days 2-4 (high-risk). The incidences of DS were 3.0% and 5.7% in ATO (n = 33) and RIF (n = 35) arms (p = 0.590), and 10.3% and 0% in patients with and without differentiation-related hyperleukocytosis (p = 0.04), respectively. Moreover, in patients with differentiation-related hyperleukocytosis, the incidence of DS was not significantly different between ATO and RIF arms. The dynamic changes of leukocyte count between arms were not statistically different. However, patients with leukocyte count > 2.61 × 109/L or percentage of promyelocytes in peripheral blood > 26.5% tended to develop hyperleukocytosis. The improvement of coagulation indexes in ATO and RIF arms was similar, with fibrinogen and prothrombin time having the quickest recovery rate. This study showed that the incidence of DS and recovery of coagulopathy are similar when treating pediatric APL with RIF or ATO.

Vincristine and dexamethasone pulses in addition to maintenance therapy among pediatric acute lymphoblastic leukemia (GD-ALL-2008): An open-label, multicentre, randomized, phase III clinical trial.

The efficacy and safety on the addition of vincristine (VCR) and dexamethasone (DEX) pulses to maintenance therapy among childhood acute lymphoblastic leukemia (ALL) remain uncertain. Herein, we perform an open-label, multicentre, randomized, phase III clinical trial that was conducted at nine major medical centers in Guangdong Province, China. Patients were randomly assigned either the conventional maintenance therapy (control group, n = 384) or the VCR/DEX pulse (treatment group, n = 375). When limited to the SR cohort, 10-year EFS was 82.6% (95% CI: 75.9-89.9) in the control group and 80.7% (95% CI: 74-88.1) in the treatment group (pnon-inferiority  = .0002). Similarly, patients with IR also demonstrated non-inferiority of the treatment group to the control group in terms of 10-year EFS (73.6% [95% CI: 67.6-80] vs. 77.6% [95% CI: 71.8-83.9]; pnon-inferiority  = .005). Among the HR cohort, compared with the control group, patients in the treatment group experienced a significant benefit in terms of 10-year EFS (61.1% [95% CI: 47.7-78.2] vs. 72.6% [95% CI: 55.6-94.7], p = .026) and a trend toward higher 10-year OS (73.8% [95% CI: 61.6-88.4] vs. 87.9% [95% CI: 579.2-97.5], p = .068). In the HR cohort, the total rate of drug-induced liver injury and Grade 3 chemotherapy-induced anemia were both lower for patients in the treatment group than in the control group (55.6% vs. 100%, p = .033; 37.5% vs. 60%, p = .036). Conversely, the total prevalence of chemotherapy-induced thrombocytopenia was higher for patients in the treatment group than in the control group (88.9% vs. 40%, p = .027). Pediatric acute lymphoblastic leukemia with high risk is suitable to VCR/DEX pulse during maintenance phase for the excellent outcome, while the standard-to-intermediate-risk patients could eliminate the pulses.

Development and refinement of diagnostic and therapeutic strategies for managing patients with cardiogenic stroke: An arduous journey.

Cardioembolic stroke, referred to as cardiogenic stroke, is a clinical syndrome in which emboli from the heart pass through the circulatory system and cause cerebral artery embolism and corresponding brain dysfunction. Compared to other subtypes of ischemic stroke, cardiogenic stroke presents with more etiologies, greater severity, worse prognosis, and a higher recurrence rate. In this minireview, we provide new insights into the etiological classification, diagnostic methods, and interventions of cardiogenic stroke.

The effect of arteriosclerosis on new-onset renal damage in diabetic patients.

The aim of this study was to investigate the effect of arteriosclerosis on new-onset renal damage in a Chinese community population with diabetes. Patients with diabetes who had attended at least one physical examination after the Brachial-ankle pulse wave velocity (BaPWV) test from 2010 to 2018 were selected as subjects. A total of 4,462 patients were included in the study cohort. BaPWV levels <1,400 cm/s, 1,400-1,799 cm/s, and ≥1,800 cm/s were applied to divide the subjects into a normal arterial stiffness group, borderline atherosclerosis group and atherosclerosis group. Renal damage was defined by isolated proteinuria, isolated eGFR <60 mL/min/1.73 m2, proteinuria and eGFR <60 mL/min/1.73 m2. A Cox proportional risk model was used to analyze the effect of different groups on new-onset renal damage. After a median follow-up of 2.85 (1.88-4.90) years, Cox proportional risk models showed that after adjusting for risk factors, compared with the normal group, the HR and 95% CI of the risk of new-onset renal damage were 1.29 (95% CI: 0.95-1.76) and 1.59 (95% CI: 1.14-2.22) in the borderline atherosclerosis group and the atherosclerosis group, respectively. Atherosclerosis is a risk factor for new-onset renal damage, especially new-onset proteinuria, in diabetic patients.

Prognostic significance of CNSL at diagnosis of childhood B-cell acute lymphoblastic leukemia: A report from the South China Children's Leukemia Group.

Objectives: The prognostic significance of acute lymphoblastic leukemia (ALL) patients with central nervous system leukemia (CNSL) at diagnosis is controversial. We aimed to determine the impact of CNSL at diagnosis on the clinical outcomes of childhood B-cell ALL in the South China Children's Leukemia Group (SCCLG). Methods: A total of 1,872 childhood patients were recruited for the study between October 2016 and July 2021. The diagnosis of CNSL depends on primary cytological examination of cerebrospinal fluid, clinical manifestations, and imaging manifestations. Patients with CNSL at diagnosis received two additional courses of intrathecal triple injections during induction. Results: The frequency of CNLS at the diagnosis of B-cell ALL was 3.6%. Patients with CNSL at diagnosis had a significantly higher mean presenting leukocyte count (P = 0.002) and poorer treatment response (P <0.05) compared with non-CNSL patients. Moreover, CNSL status was associated with worse 3-year event-free survival (P = 0.030) and a higher risk of 3-year cumulative incidence of relapse (P = 0.008), while no impact was observed on 3-year overall survival (P = 0.837). Multivariate analysis revealed that CNSL status at diagnosis was an independent predictor with a higher cumulative incidence of relapse (hazard ratio = 2.809, P = 0.016). Conclusion: CNSL status remains an adverse prognostic factor in childhood B-cell ALL, indicating that additional augmentation of CNS-directed therapy is warranted for patients with CNSL at diagnosis.

Facile fabrication of micropattern surfaces with controlled wettability on PDMS-modified fiber membranes for cell patterning.

Various cell culture substrates have been developed for cell patterning to control cell distributions and orientations in tissue engineering, drug screening and regenerative medicine. In this study, a preparation method of modified fiber membranes was applied in the field of cell patterning, and the obtained fiber membranes guided the cell distributions and orientations flexibly. The aligned electrospinning fiber membranes were dip-coated with polydimethylsiloxane (PDMS) to improve the stability of wettability, and then it was treated with oxygen plasma with a photomask to obtain a hydrophilic-hydrophobic surface micropattern. The morphologies, wettabilities and chemical structures of the membranes were analyzed by using a scanning electron microscope (SEM), drop shape analysis instrument, energy dispersive spectrometer (EDS) and Fourier transform infrared (FTIR) spectrometer. The L929 cells were cultured on the obtained membranes to observe the controlled cell distributions and orientations by using a SEM and fluorescence microscope. The results indicate that the treated membranes have the ability to control both cell distributions and orientations simultaneously. This method offers a novel approach to develop cell culture substrates for cell patterning in tissue engineering.

Single-cell patterning regulation by physically modified silicon nanostructures.

Chemically and biologically modified substrates for single-cell patterning have been studied extensively, but physically modified structures for single-cell patterning still need further study. In this paper, physically modified silicon nanostructures were introduced to study their effect on SHSY5Y cells. Double-beam double exposure laser interference lithography combined with metal-assisted etching (MACE) was used to fabricate the physically modified silicon nanostructures. It was found that the cells on the gratings stretched and grew orderly along the grating with a small cell area and almost the same cell length compared with those on the Si wafer (control group). While on the grids, the cells were round with limited spreading, grew independently and had the smallest cell area and cell length. Moreover, the localization ratio of cells adhered onto the areas of nanopillars in the grid structures with different periods has been investigated. The results suggest that the physically modified grid silicon nanostructures can regulate the single-cell localization growth and the rational design of substrate structures can maximize the single-cell localization ratio. The findings provide guidance for the design of physically modified nanostructures and regulating single cell patterning, and a better understanding of single-cell localized growth.

A Nomogram for Predicting Event-Free Survival in Childhood Acute Lymphoblastic Leukemia: A Multicenter Retrospective Study.

Objective: Even though childhood acute lymphoblastic leukemia (ALL) has an encouraging survival rate in recent years, some patients are still at risk of relapse or even death. Therefore, we aimed to construct a nomogram to predict event-free survival (EFS) in patients with ALL. Method: Children with newly diagnosed ALL between October 2016 and July 2021 from 18 hospitals participating in the South China children's leukemia Group (SCCLG) were recruited and randomly classified into two subsets in a 7:3 ratio (training set, n=1187; validation set, n=506). Least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were adopted to screen independent prognostic factors. Then, a nomogram can be build based on these prognostic factors to predict 1-, 2-, and 3-year EFS. Concordance index (C-index), area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance and clinical utility of nomogram. Result: The parameters that predicted EFS were age at diagnosis, white blood cell at diagnosis, immunophenotype, ETV6-RUNX1/TEL-AML1 gene fusion, bone marrow remission at day 15, and minimal residual disease at day 15. The nomogram incorporated the six factors and provided C-index values of 0.811 [95% confidence interval (CI) = 0.792-0.830] and 0.797 (95% CI = 0.769-0.825) in the training and validation set, respectively. The calibration curve and AUC revealed that the nomogram had good ability to predict 1-, 2-, and 3-year EFS. DCA also indicated that our nomogram had good clinical utility. Kaplan-Meier analysis showed that EFS in the different risk groups stratified by the nomogram scores was significant differentiated. Conclusion: The nomogram for predicting EFS of children with ALL has good performance and clinical utility. The model could help clinical decision-making.

Senescent skeletal cells cross-talk with synovial cells plays a key role in the pathogenesis of osteoarthritis.

Osteoarthritis (OA) has been recognized as an age-related degenerative disease commonly seen in the elderly that affects the whole "organ" including cartilage, subchondral bone, synovium, and muscles. An increasing number of studies have suggested that the accumulation of senescent cells triggering by various stresses in the local joint contributes to the pathogenesis of age-related diseases including OA. In this review, we mainly focus on the role of the senescent skeletal cells (chondrocytes, osteoblasts, osteoclasts, osteocyte, and muscle cells) in initiating the development and progression of OA alone or through cross-talk with the macrophages/synovial cells. Accordingly, we summarize the current OA-targeted therapies based on the abovementioned theory, e.g., by eliminating senescent skeletal cells and/or inhibiting the senescence-associated secretory phenotype (SASP) that drives senescence. Furthermore, the existing animal models for the study of OA from the perspective of senescence are highlighted to fill the gap between basic research and clinical applications. Overall, in this review, we systematically assess the current understanding of cellular senescence in OA, which in turn might shed light on the stratified OA treatments.

YAP/miR-524-5p axis negatively regulates TXNIP expression to promote chondrosarcoma cell growth.

Chondrosarcoma (CHS) is the second most common bone malignant tumor and currently has limited treatment options. We have recently demonstrated that thioredoxin interacting protein (TXNIP) plays a crucial role in the oncogenesis of bone sarcoma, yet its implication in CHS is underdetermined. In the present study, we first found that knockdown of TXNIP promotes the proliferation of CHS cell largely through increasing their glycolytic metabolism, which is well-known as Warburg effect for providing energy. Consistent with our previous report that YAP is fundamental for CHS cell growth, herein we revealed that YAP functioned as an upstream molecule of TXNIP, and that YAP negatively regulated TXNIP mRNA and protein expression both in vitro and in vivo. Mechanistically, although knockdown of YAP upregulated both the nuclear and cytoplasmic TXNIP expression, we did not observe any obvious interaction between YAP and TXNIP; instead, miRNA-524-5p was demonstrated to be required for YAP-regulated TXNIP expression and thus controlling CHS cell growth. Together, our study reveals that TXNIP is a tumor suppressor in terms of CHS, and that the YAP/miRNA-524-5p/TXNIP signaling axis may provide a novel clue for CHS targeted therapy.

Uncertainty-guided graph attention network for parapneumonic effusion diagnosis.

Parapneumonic effusion (PPE) is a common condition that causes death in patients hospitalized with pneumonia. Rapid distinction of complicated PPE (CPPE) from uncomplicated PPE (UPPE) in Computed Tomography (CT) scans is of great importance for the management and medical treatment of PPE. However, UPPE and CPPE display similar appearances in CT scans, and it is challenging to distinguish CPPE from UPPE via a single 2D CT image, whether attempted by a human expert, or by any of the existing disease classification approaches. 3D convolutional neural networks (CNNs) can utilize the entire 3D volume for classification: however, they typically suffer from the intrinsic defect of over-fitting. Therefore, it is important to develop a method that not only overcomes the heavy memory and computational requirements of 3D CNNs, but also leverages the 3D information. In this paper, we propose an uncertainty-guided graph attention network (UG-GAT) that can automatically extract and integrate information from all CT slices in a 3D volume for classification into UPPE, CPPE, and normal control cases. Specifically, we frame the distinction of different cases as a graph classification problem. Each individual is represented as a directed graph with a topological structure, where vertices represent the image features of slices, and edges encode the spatial relationship between them. To estimate the contribution of each slice, we first extract the slice representations with uncertainty, using a Bayesian CNN: we then make use of the uncertainty information to weight each slice during the graph prediction phase in order to enable more reliable decision-making. We construct a dataset consisting of 302 chest CT volumetric data from different subjects (99 UPPE, 99 CPPE and 104 normal control cases) in this study, and to the best of our knowledge, this is the first attempt to classify UPPE, CPPE and normal cases using a deep learning method. Extensive experiments show that our approach is lightweight in demands, and outperforms accepted state-of-the-art methods by a large margin. Code is available at https://github.com/iMED-Lab/UG-GAT.