Achieving Ideal and Environmentally Stable n-Type Charge Transport in Polymer Field-Effect Transistors.

Realizing ideal charge transport in field-effect transistors (FETs) of conjugated polymers is crucial for evaluating device performance, such as carrier mobility and practical applications of conjugated polymers. However, the current FETs using conjugated polymers as the active layers generally show certain non-ideal transport characteristics and poor stability. Here, ideal charge transport of n-type polymer FETs is achieved on flexible polyimide substrates by using an organic-inorganic hybrid double-layer dielectric. Deposited conjugated polymer films show highly ordered structures and low disorder, which are supported by grazing-incidence wide-angle X-ray scattering, near-edge X-ray absorption fine structure, and molecular dynamics simulations. Furthermore, the organic-inorganic hybrid double-layer dielectric provides low interfacial defects, leading to excellent charge transport in FETs with high electron mobility (1.49 ± 0.46 cm2 V-1 s-1) and ideal reliability factors (102 ± 7%). Fabricated polymer FETs show a self-encapsulation effect, resulting in high stability of the FET charge transport. The polymer FETs still work with high mobility above 1 cm2 V-1 s-1 after storage in air for more than 300 days. Compared with state-of-the-art conjugated polymer FETs, this work simultaneously achieves ideal charge transport and environmental stability in n-type polymer FETs, facilitating rapid device optimization of high-performance polymer electronics.

PET/NIR Fluorescence Bimodal Imaging for Targeted Tumor Detection.

Cancer is one of the greatest threats to human health due to late diagnosis and incomplete resection. The bimodal probe combines positron emission tomography (PET) imaging for noninvasive whole-body scanning with intraoperative near-infrared fluorescence (NIRF) surgical guidance for preoperative tumor detection, tumor resection during surgery, and postoperative monitoring. We developed a new PET/NIRF bimodal imaging agent, [68Ga]Ga-DOTA-NPC, covalently coupled to DCDSTCY and DOTA via ethylenediamine and radiolabeled with gallium-68, and investigated it in vitro and in vivo. The probe was found to be preferential for colon cancer cells due to the organic anion-transporting polypeptide1B3 (OATP1B3). PET/NIRF imaging allowed us to confirm [68Ga]Ga-DOTA-NPC as a promising probe for tumor detection, as it provides good biosafety and high-contrast tumor accumulation. Orthotopic and subcutaneous colon tumors were successfully resected under real-time NIRF guidance. [68Ga]Ga-DOTA-NPC provides highly sensitive and unlimited tissue-penetrating PET/NIRF imaging, helping to visualize and differentiate tumors from adjacent tissue.

Tumor-Targeting NIRF/MR Dual-Modal Molecular Imaging Probe for Surgery Navigation.

Multimodality imaging recognized as a promising monitoring strategy can serve the needs of accurate diagnosis and treatment of cancer by providing molecular and anatomic information about tumor sites. However, the probes based on multiple imaging modalities for surgery navigation remain limited due to poor biocompatibility and tumor targeting specificity. Herein, we present a small-molecule near-infrared fluorescence/magnetic resonance (NIRF/MR) imaging probe, Gd-NMC-3, covalently coupled with DCDSTCY and Gd-DOTA via butane diamine, for precise detection and intraoperative visualization. The in vitro and in vivo studies demonstrated that Gd-NMC-3 could be effectively accumulated in tumor sites as a bimodal imaging molecule exhibiting significant fluorescence accumulation and reasonable relaxation property in tumors with low cytotoxicity and good biocompatibility. Furthermore, Gd-NMC-3 was successfully applied to provide real-time visual navigation in LM3 orthotopic and subcutaneous tumor models to guide the resection of tumors. Importantly, no more fluorescence was observed in mice after operation, implying the total removal of tumor tissues. In conclusion, Gd-NMC-3 has great potential to be applied in the clinic based on its high resolution and sensitivity in tumor imaging.

Controlling Solution-State Aggregation and Solid-State Microstructures of Conjugated Polymers by Tuning Backbone Conformation.

Molecular ordering of conjugated polymers both in solution-state aggregates and in solid-state microstructures is a determining factor of the charge transport properties in optoelectronic devices. However, the effect of backbone conformation in conjugated polymers on assembly structures is still unclear. Herein, to understand such backbone conformation effect, three novel chlorinated benzodifurandionge-based oligo(p-phenylene vinylene) (BDOPV) polymers are systematically developed. These BDOPV-based polymers exhibit significantly twisted backbone conformation (near 90° interunit torsion angle) between conjugated units, which can prevent polymer chains from forming ordered assembly structures by increasing conformational energy penalty in closely packed chains. A higher rotational barrier of the torsion angle would further prevent polymer chains from assembling, finally resulting in nonaggregated chains in solution and highly disordered solid-state packing structures. This work will deepen the understanding of the relationship between polymer backbone conformation and assembly structures, contributing to the exploration of the structure-property relationship of polymers.

Regulation of High Miscibility for Efficient Charge-Transport in n-Doped Conjugated Polymers.

Strong interchain interactions of conjugated polymers usually result in poor miscibility with molecular dopants, limiting the doping efficiency because of uncontrolled phase separation. We have developed a strategy to achieve efficient charge-transport and high doping miscibility in n-doped conjugated polymers. We solve the miscibility issue through disorder side-chains containing dopants better. Systemic structural characterization reveals a farther side-chain branching point will lead to higher disorders, which provides appropriate sites to accommodate extrinsic molecular dopants without harming original chain packings and charge-transport channels. Therefore, better sustainability of solid-state microstructure is obtained, yielding a stable conductivity even when overloading massive dopants. This work highlights the importance of realizing high host-dopant miscibility in molecular doping of conjugated polymers.

Multi-level aggregation of conjugated small molecules and polymers: from morphology control to physical insights.

Aggregation of molecules is a multi-molecular phenomenon occurring when two or more molecules behave differently from discrete molecules due to their intermolecular interactions. Moving beyond single molecules, aggregation usually demonstrates evolutive or wholly emerging new functionalities relative to the molecular components. Conjugated small molecules and polymers interact with each other, resulting in complex solution-state aggregates and solid-state microstructures. Optoelectronic properties of conjugated small molecules and polymers are sensitively determined by their aggregation states across a broad range of spatial scales. This review focused on the aggregation ranging from molecular structure, intermolecular interactions, solution-state assemblies, and solid-state microstructures of conjugated small molecules and polymers. We addressed the importance of such aggregation in filling the gaps from the molecular level to device functions and highlighted the multi-scale structures and properties at different scales. From the view of multi-level aggregation behaviors, we divided the whole process from the molecule to devices into several parts: molecular design, solvation, solution-state aggregation, crystal engineering, and solid-state microstructures. We summarized the progress and challenges of relationships between optoelectronic properties and multi-level aggregation. We believe aggregation science will become an interdisciplinary research field and serves as a general platform to develop future materials with the desired functions.

Combined topical and intravenous administration of tranexamic acid further reduces postoperative blood loss in adolescent idiopathic scoliosis patients undergoing spinal fusion surgery: a randomized controlled trial.

BACKGROUND: To indicate whether combined topical and intravenous (IV) administration of tranexamic acid (TXA) could further reduce the blood loss after surgery for adolescent idiopathic scoliosis (AIS) compared with IV-TXA alone. METHODS: Ninety AIS patients who underwent posterior spinal fusion were prospectively randomized to combined group (IV + topical- TXA group) and IV-TXA alone group. TXA was infused at a loading dose of 1 g from the beginning of the surgery with a maintenance dose of 10 mg/kg/h until the wound was closed. In the combined group, 2 g TXA was injected retrogradely through a drain, while an equivalent amount of normal saline was injected in the IV-TXA alone group. The drain tube was clamped for 2 h in both groups. The amount of wound drainage and transfusion rates were analyzed. RESULTS: The drainage volume and duration of drain were significantly lower in the combined group compared with that in the IV-TXA alone group (372.0 ± 129.7 mL vs. 545.2 ± 207.7 mL, P < 0.001;64.7 ± 13.9 h vs. 82.0 ± 12.5 h, P < 0.001). Postoperative length of hospital stay was also significantly shorter in the combined group (6.5 ± 1.51 days vs. 7.95 ± 1.44 days, P < 0.05). Transfusion and complication rates were comparable between the two groups . CONCLUSIONS: IV injection of TXA combined with retrograde injection of TXA into a drain and clamping it for 2 h could further reduce the total volume of drainage in AIS patients who underwent spinal fusion surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900024177 , Registered 29 June 2019, http://www.chictr.org.cn/showproj.aspx?proj=40214.

Correlating Charge Transport Properties of Conjugated Polymers in Solution Aggregates and Thin-Film Aggregates.

The role of solution aggregates on the charge transport process of conjugated polymers in electronic devices has gained increasing attention; however, the correlation of the charge carrier mobilities between the solution aggregates and the solid-state films remains elusive. Herein, three polymers, FBDOPV-2T, FBDOPV-2F2T, and FBDOPV-4F2T, are designed and synthesized with distinct aggregation behavior in solution. By combining contact-free ultrafast terahertz (THz) spectroscopy and field-effect transistor measurements, we track the charge carrier mobility of the aggregates of these polymers from the solution to the thin-film state. Remarkably, the mobility of these three polymers is found to follow nearly the same trend (FBDOPV-2T>FBDOPV-2F2T≫FBDOPV-4F2T) in both solutions and thin-film states. The quantitative mobility correlation indicates that the charge transport properties of solution aggregates play a critical role in determining the thin-film charge transport properties and final device performance. Our results highlight the importance of investigating and controlling solution aggregation structures towards efficient organic electronic devices.

Sac Embolization and Side Branch Embolization for Preventing Type II Endoleaks After Endovascular Aneurysm Repair: A Meta-analysis.

Purpose:To investigate the efficacy and safety of preoperative side branch embolization or intraoperative sac embolization for preventing type II endoleaks after endovascular aneurysm repair (EVAR). Materials and Methods: A systematic literature search of MEDLINE and EMBASE was performed to identify studies that evaluated the outcomes of sac embolization vs no embolization or side branch embolization vs no embolization in patients who received EVAR. Among the 904 studies screened, 17 studies with 2084 participants were included in this review. Outcome measures included the type II endoleak rate, the reintervention rate for type II endoleaks, the incidence of types I/III endoleaks, and the rate of complications. Fixed (no heterogeneity) or random effects models were constructed for each outcome; the results are presented as the odds ratio (OR) with 95% confidence interval (CI). Results: The sac embolization group had significantly lower type II endoleak (OR 0.21, 95% CI 0.13 to 0.34, p<0.001) and reintervention (OR 0.15, 95% CI 0.07 to 0.33, p<0.001) rates than the no embolization group. No significant differences between the 2 groups were found for the type I/III endoleak rate (OR 0.57, 95% CI 0.23 to 1.37, p=0.21) or complication rate (OR 1.22, 95% CI 0.32 to 4.70, p=0.77). Compared with no embolization, side branch embolization was also associated with a decrease in type II endoleak (OR 0.35, 95% CI 0.21 to 0.60, p<0.001) and reinterventions (OR 0.10, 95% CI 0.04 to 0.27, p<0.001). One severe procedure-related complication (fatal colon ischemia) was reported in the side branch embolization group. Conclusion: Sac embolization and side branch embolization are safe and effective in preventing type II endoleaks. Further randomized trials are needed to directly compare the clinical outcomes of these procedures.

Ordered Solid-State Microstructures of Conjugated Polymers Arising from Solution-State Aggregation.

Controlling the solution-state aggregation of conjugated polymers for producing specific microstructures remains challenging. Herein, a practical approach is developed to finely tune the solid-state microstructures through temperature-controlled solution-state aggregation and polymer crystallization. High temperature generates significant conformation fluctuation of conjugated backbones in solution, which facilitates the polymer crystallization from solvated aggregates to orderly packed structures. The polymer films deposited at high temperatures exhibit less structural disorders and higher electron mobilities (up to two orders of magnitude) in field-effect transistors, compared to those deposited at low temperatures. This work provides an effective strategy to tune the solution-state aggregation to reveal the relationship between solution-state aggregation and solid-state microstructures of conjugated polymers.

The effects of particle density in moxa smoke on the ultrastructure of knee cartilage and expressions of TNF-α, IL-1b, BAX, and Bcl-2 mRNA in a rat model for osteoarthritis.

BACKGROUND: The effectiveness of smokeless moxa and other means to reduce exposure are extensively investigated with regards to the health consequences of inhalation of moxa smoke, and clinical studies indicate that classical moxibustion is superior to smokeless moxa. This study aims to quantify the effects of particle density in moxa smoke on the clinical outcome with an established model, demonstrated to be effective for classical moxibustion. OBJECTIVES: The purpose of this study is to explore the effects of particle density in moxa smoke on the ultrastructure of knee cartilage and expression of cytokine, tissue necrosing factor-alpha (TNF-α), interleukin 1 beta (IL-1b), apoptosis regulator, B-cell lymphoma-2 (Bcl-2), and BAX in a rat model for inflammatory joint disease. METHODS: Fifty healthy experimental rats were randomly divided into five groups, including normal control, model control, and moxa exposure groups with low, medium, and high particle density, and n = 10/group. In addition, a knee osteoarthritis model was duplicated in the model control and moxa exposure groups. Finally, the ultrastructure of knee cartilage was observed using transmission electron microscopy, and messenger RNA (mRNA) expressions of TNF-α, IL-1b, BAX, and Bcl-2 were determined with quantitative fluorescence methodology. RESULTS: In the model control and moxa exposure groups, knee cartilage indicated that histologic changes with the degree of injury were inversely proportional to moxa smoke density. The mRNA expressions of TNF-α, IL-1b, and BAX in synovial fluid, as an acute phase reactant, were similarly inversely related to moxa smoke density, but significantly increased. In contrast, Bcl-2, as an antiapoptotic, was substantially decreased in the model, while its levels were directly proportional to moxa smoke density. Besides, the ratio of Bcl-2/BAX mRNA was sharply decreased in the model group, but with levels proportional to moxa smoke density. CONCLUSIONS: A correlation was found between the particle density in moxa smoke and degree of injury to knee cartilage, favoring higher particle densities. This can be partially related to the suppression of the inflammatory effects of TNF-α, IL-1b, enhancement of the antiapoptotic effects of Bcl-2, and, nevertheless, suppression of the apoptotic effects of BAX. Finally, the protective effect of antiapoptotic is one of the key mechanisms for an ambient moxa smoking environment.

[Complications and prophylaxis strategies of posterior hemivertebra resection for congenital scoliosis].

OBJECTIVE: To evaluate the surgical outcomes and related complications of posterior hemivertebra resection with transpedicular instrumentation in the treatment of congenital scoliosis caused by fully-segmented non-incarcerated hemivertebra. METHODS: From January 2003 to January 2012, one hundred and forty consecutive cases of congenital scoliosis treated by posterior hemivertebra resection with transpedicular instrumentation were investigated retrospectively. Radiographs were reviewed to determine the type and location of the hemivertebra, the coronal curve magnitude, sagittal alignment, compensatory cranial curve and compensatory caudal curve preoperatively, postoperatively and at the latest follow-up. Operative reports and patient charts were reviewed to record operation time, fusion level and complications. RESULTS: One hundred and fifty-one posterior hemivertebra resections in 140 patients aged 2 to 45 years (average 10.8 years) with non-incarcerated hemivertebra were evaluated. All the patients were followed up from 3 to 119 months (average 25 months). The average fusion level was 5.0 segments (2-11 segments). There was a mean improvement of 71.3% in the segmental scoliosis from 42.5° before surgery to 10.6° at the time of the latest follow-up, and a mean improvement of 66.8% in segmental kyphosis from 29.5° to 7.2° at the same periods. There were 14 complications (13 patients), 3 pedicle fractures, 2 rod breakages, 2 pedicle elongation, 2 removed implants for prominent implants, 2 delayed wound healing, 2 additional surgeries for curve progression, 1 prolonged respiratory support. There was no neurological complication. CONCLUSIONS: Posterior hemivertebra resection with transpedicular instrumentation is a safe and effective procedure for congenital scoliosis patients.Neurological complication is rare, but implant-related complication still remains a challenge.

Br-Vacancies Induced Variable Ranging Hopping Conduction in High-Order Topological Insulator Bi4Br4.

The defects have a remarkable influence on the electronic structures and the electric transport behaviors of the matter, providing the additional means to engineering their physical properties. In this work, a comprehensive study on the effect of Br-vacancies on the electronic structures and transport behaviors in the high-order topological insulator Bi4Br4 is performed by the combined techniques of the scanning tunneling microscopy (STM), angle-resolved photoemission spectroscopy (ARPES), and physical properties measurement system along with the first-principle calculations. The STM results show the defects on the cleaved surface of a single crystal and reveal that the defects are correlated to the Br-vacancies with the support of the simulated STM images. The role of the Br-vacancies in the modulation of the band structures has been identified by ARPES spectra and the calculated energy-momentum dispersion. The relationship between the Br-vacancies and the semiconducting-like transport behaviors at low temperature has been established, implying a Mott variable ranging hopping conduction in Bi4Br4. The work not only resolves the unclear transport behaviors in this matter, but also paves a way to modulate the electric conduction path by the defects engineering.

[Advances in minimally invasive spine surgery in treatment of adolescent idiopathic scoliosis and adult scoliosis].

The traditional treatment of scoliosis is mainly based on open surgeries that use the anterior approach, the posterior approach, or both. These surgical procedures often lead to complications including massive blood loss, infections, and pain of incision.The minimally invasive spine surgery (MISS) was introduced in the 1990s and has shown many advantages including less blood loss, less pain, and lower infection incidences.Today MISS is mainly used in the treatment of adolescent idiopathic scoliosis and adult scoliosis. However, due to some inevitable complications, it still can not be routinely applied.This review will briefly summarize the advances in the application of MISS in surgical treatment of adolescent idiopathic scoliosis and adult scoliosis.

[Effects of guanxinping tablet containing serum on H2O2-induced apoptosis and NF-kappaB expressions in vascular endothelial cells].

OBJECTIVE: To study the effects of Guanxinping Tablet (GT) containing serum on H2O2-induced apoptosis and the nuclear factor kappa B (NF-kappaB) expression in vascular endothelial cells (VECs). METHODS: Rabbits were randomly divided into the normal control group (treated with normal saline, 10 mL/kg), the verapamil group (0. 02 g/kg, 10 mL/kg), the small dose GT group (2; 8 g/kg, 10 mL/kg), the middle dose GT group (5.6 g/kg, 10 mL/kg), and the large dose GT group (11.2 g/kg, 10 mL/kg), 3 in each group. The medication was given to rabbits by gastrogavage for 3 successive days. The gastrogavage was performed twice on the last day with an interval of 2 h. One h after the last medication the peripheral blood was sampled from the vein of the ear edge. The blood was put for 1 h and centrifuged at 2 500 r/min for 30 min. The serum was extracted and deactivated at 56 degrees C for 30 min to prepare the drug containing serum. The apoptosis injury model was established using 100 micromol/L H2O2 induced VECs in the log phase growth. After modeling they were divided into 6 groups, 5 samples in each group, i. e., the normal group (10% vehicle serum culture solution), the model group (10% vehicle serum culture solution +100 micromol/L H2O2), the verapamil group (10% verapamil serum culture solution +100 micromol/L H2O2), the low dose GT group (10% low dose GT culture solution +100 micromol/L H2O2), the middle dose GT group (10% middle dose GT culture solution + 100 micromol/L H2O2), and the high dose GT group (10% high dose GT culture solution + 100 micromol/L H2O2). THE VEC apoptotic rate was detected using flow cytometry. The protein expression of NF-kappaB was detected using Western blot. RESULTS: The VEC apoptosis rate (9.00% +/- 1.18%) and the protein expression of NF-kappaB (0.39% +/- 0.06%) increased more in the model group than in the normal control group (P<0.01). Compared with the model group, the VEC apoptosis rate of the verapamil group (6.00% +/- 0.18%), the large dose GT group (5.30% +/- 0.08%), and the middle dose GT group (6.83% +/- 0.51%) were obviously lower. The expression of NF-kappaB of each treatment group significantly decreased (the verapamil group: 0.28% +/- 0.03%; the small dose GT group: 0.33% +/- 0.03%; the middle dose GT group: 0.30% +/- 0.03%; the large dose GT group: 0.28% +/- 0.04%, P<0.01, P<0.05). CONCLUSIONS: GT could fight against H2O2-induced VEC cell apoptosis. Its mechanism might be correlated with regulating the expression of NF-kappaB protein.

[Treadmill exercise test in patients with coronary artery myocardial bridging].

OBJECTIVE: To observe treadmill exercise test (TET) characteristics in patients with myocardial bridging (MB). METHODS: TET results from January 2003 to December 2010 were retrospectively analyzed in 156 patients with confirmed MB diagnosis. MB patients were divided into smoking group (68 cases) and non-smoking group (88 cases). Coronary angiography results were used to analyze the relations between MB length, myocardial ischemia and exercising duration. RESULTS: (1) MB was documented on two coronary arteries in 2 patients (1%), MB was detected in single artery in 154 patients (99%), of whom 146 cases were located at left anterior descending artery, 8 cases were located at right coronary artery. The degree of narrowing of MB was graded 1 (less than 50%) in 16 patients (10%), grade 2 (50% to 75%) in 108 patients (69%) and grade 3 (greater than 75%) in 32 patients (21%). The length of MB ranged between 4 to 40 mm, MB length was less than 10 mm in 40 patients (26%), between 11 to 20 mm in 48 patients (31%), between 21 to 30 mm in 44 patients (28%), greater than 31 mm in 24 patients (15%). (2) TET positive rate was 41% (64/156) and the TET positive rate was significantly higher in smoking group than in non-smoking group [57% (39/68) vs. 28% (25/88, P < 0.01)]. (3) The length of MB was positively related to the ST-segment depression (r = 0.723, P < 0.01) and negatively related to exercising duration (r = -0.828, P < 0.01). Heart rate was positively related to the ST-segment depression (r = 0.368, P < 0.01). CONCLUSIONS: TET may serve as a good test to assess myocardial ischemia in patients with MB. The length of MB is positively related with myocardial ischemia and negatively related with exercising duration. Smoking might increase myocardial ischemic incidence in MB patients, MB patients should be advised to stop smoking.

Machine Learning Approaches to Define Candidates for Ambulatory Single Level Laminectomy Surgery.

STUDY DESIGN: retrospective cohort study. OBJECTIVES: To test and compare 2 machine learning algorithms to define characteristics associated with candidates for ambulatory same day laminectomy surgery. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for patients who underwent single level laminectomy in 2017 and 2018. The main outcome was ambulatory same day discharge. Study variables of interest included demographic information, comorbidities, preoperative laboratory values, and intra-operative information. Two machine learning predictive modeling algorithms, artificial neural network (ANN) and random forest, were trained to predict same day discharge. The quality of models was evaluated with area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) measures. RESULTS: Among 35,644 patients, 13,230 (37.1%) were discharged on the day of surgery. Both ANN and RF demonstrated a satisfactory model quality in terms of AUC (0.77 and 0.77), accuracy (0.69 and 0.70), sensitivity (0.83 and 0.58), specificity (0.55 and 0.80), PPV (0.77 and 0.69), and NPV (0.64 and 0.70). Both models highlighted several important predictive variables, including age, duration of operation, body mass index and preoperative laboratory values including, hematocrit, platelets, white blood cells, and alkaline phosphatase. CONCLUSION: Machine learning approaches provide a promising tool to identify candidates for ambulatory laminectomy surgery. Both machine learning algorithms highlighted the as yet unrecognized importance of preoperative laboratory testing on patient pathway design.

Primary clinical evaluation of the joint replacement for the treatment of the first metatarsophalangeal arthritis.

OBJECTIVE: To retrospectively assess the primary clinical results of a cohort of the first metatarsophalangeal joint replacement with double-stemmed hinge silicone implant. METHODS: A total of 12 patients (15 feet) received the joint replacement with double-stemmed hinge silicone implant. There were 2 males and 10 females with a mean age of 61.4 (range, 56-75) years old. Of them, 9 cases (11 feet) were hallux valgus with osteoarthritis; 1 case (2 feet) was rheumatic arthritis; 2 cases (2 feet) were traumatic arthritis. The subjective and objective results were evaluated during follow-up. RESULTS: All of the patients were followed up regularly with an average of 24.7 months, ranging from 12 to 38 months. Ten patients were completely satisfied with the operation; 1 patient showed partial satisfaction, and 1 patient was not satisfied because of the first matatarsophalangeal joint pain due to severe hyperosteogeny surrounding the cut bone surface 3 years after the operation. Osteolysis around the implant occurred in 2 cases without clinical symptoms, and no special treatment was given. CONCLUSION: The joint replacement is a preferable method in alleviating pain and improving walking function with proper indication.

Analysis of crucial genes, pathways and construction of the molecular regulatory networks in vascular smooth muscle cell calcification.

Vascular calcification (VC) accompanies the trans-differentiation of vascular smooth muscle cells (VSMCs) into osteo/chondrocyte-like cells and resembles physiological bone mineralization. However, the molecular mechanisms underlying VC initiation and progression have remained largely elusive. The aim of the present study was to identify the genes and pathways common to VSMC and osteoblast calcification and construct a regulatory network of non-coding RNAs and transcription factors (TFs). To this end, the Gene Expression Omnibus dataset GSE37558 including mRNA microarray data of calcifying VSMCs (CVSMCs) and calcifying osteoblasts (COs) was analyzed. The differentially expressed genes (DEGs) were screened and functionally annotated and the microRNA (miRNA/mRNA)-mRNA, TF-miRNA and long non-coding RNA (lncRNA)-TF regulatory networks were constructed. A total of 318 DEGs were identified in the CVSMCs relative to the non-calcified VSMCs, of which 43 were shared with the COs. The CVSMC-related DEGs were mainly enriched in the functional terms cell cycle, extracellular matrix (ECM), inflammation and chemotaxis-mediated signaling pathways, of which ECM was enriched by the DEGs for the COs as well. The protein-protein interaction network of CVSMCs consisted of 281 genes and 3,650 edges. There were 30 hub genes in this network, including maternal embryonic leucine zipper kinase (MELK), which potentially regulates the differentially expressed TF (DETF) forkhead box (FOX)M1 and is a potential target gene of Homo sapiens miR-485-3p and miR-181d. The TF-miRNA network included 251 TFs and 60 miRNAs, including 10 DETFs such as FOXO1 and snail family transcriptional repressor 2 (SNAI2). Furthermore, the lncRNAs H19 imprinted maternally expressed transcript (H19) and differentiation antagonizing non-protein coding RNA (DANCR) were predicted as the upstream regulators of FOXO1 and SNAI2 in the lncRNA-TF regulatory network. DANCR, MELK and FOXM1 were downregulated, and H19, FOXO1 and SNAI2 were upregulated in the CVSMCs. Taken together, the CVSMCs and COs exhibited similar molecular changes in the ECM. In addition, the MELK-FOXM1, H19/DANCR-FOXO1 and SNAI2 regulatory pathways likely mediate VSMC calcification.

Identification of genes, pathways and transcription factor-miRNA-target gene networks and experimental verification in venous thromboembolism.

Venous thromboembolism (VTE) is a complex, multifactorial life-threatening disease that involves vascular endothelial cell (VEC) dysfunction. However, the exact pathogenesis and underlying mechanisms of VTE are not completely clear. The aim of this study was to identify the core genes and pathways in VECs that are involved in the development and progression of unprovoked VTE (uVTE). The microarray dataset GSE118259 was downloaded from the Gene Expression Omnibus database, and 341 up-regulated and 8 down-regulated genes were identified in the VTE patients relative to the healthy controls, including CREB1, HIF1α, CBL, ILK, ESM1 and the ribosomal protein family genes. The protein-protein interaction (PPI) network and the transcription factor (TF)-miRNA-target gene network were constructed with these differentially expressed genes (DEGs), and visualized using Cytoscape software 3.6.1. Eighty-nine miRNAs were predicted as the targeting miRNAs of the DEGs, and 197 TFs were predicted as regulators of these miRNAs. In addition, 237 node genes and 4 modules were identified in the PPI network. The significantly enriched pathways included metabolic, cell adhesion, cell proliferation and cellular response to growth factor stimulus pathways. CREB1 was a differentially expressed TF in the TF-miRNA-target gene network, which regulated six miRNA-target gene pairs. The up-regulation of ESM1, HIF1α and CREB1 was confirmed at the mRNA and protein level in the plasma of uVTE patients. Taken together, ESM1, HIF1α and the CREB1-miRNA-target genes axis play potential mechanistic roles in uVTE development.