Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma.

Hepatocellular carcinoma is the third leading cause of deaths from cancer worldwide. Infection with the hepatitis B virus is one of the leading risk factors for developing hepatocellular carcinoma, particularly in East Asia1. Although surgical treatment may be effective in the early stages, the five-year overall rate of survival after developing this cancer is only 50-70%2. Here, using proteomic and phospho-proteomic profiling, we characterize 110 paired tumour and non-tumour tissues of clinical early-stage hepatocellular carcinoma related to hepatitis B virus infection. Our quantitative proteomic data highlight heterogeneity in early-stage hepatocellular carcinoma: we used this to stratify the cohort into the subtypes S-I, S-II and S-III, each of which has a different clinical outcome. S-III, which is characterized by disrupted cholesterol homeostasis, is associated with the lowest overall rate of survival and the greatest risk of a poor prognosis after first-line surgery. The knockdown of sterol O-acyltransferase 1 (SOAT1)-high expression of which is a signature specific to the S-III subtype-alters the distribution of cellular cholesterol, and effectively suppresses the proliferation and migration of hepatocellular carcinoma. Finally, on the basis of a patient-derived tumour xenograft mouse model of hepatocellular carcinoma, we found that treatment with avasimibe, an inhibitor of SOAT1, markedly reduced the size of tumours that had high levels of SOAT1 expression. The proteomic stratification of early-stage hepatocellular carcinoma presented in this study provides insight into the tumour biology of this cancer, and suggests opportunities for personalized therapies that target it.

Diurnal gene oscillations modulated by RNA metabolism in tomato.

Diurnal rhythms are known to regulate the expression of a large number of genes, coordinating plant growth and development with diel changes in light and temperature. However, the impact of RNA metabolism on rhythmic gene oscillations in plant is not yet fully understood. To address this question, we performed transcriptome and degradome profiling on tomato leaves at 6 time points during one 24 h cycle, using RNA-seq and genome-wide mapping of uncapped and cleavage transcripts (GMUCT). Time-series profiling of RNA-seq revealed 9342 diurnal-oscillated genes, which were enriched in various metabolic processes. To quantify the general level of RNA degradation for each gene, we utilized the Proportion Uncapped (PU) metric, which represents the GMUCT/RNA-seq ratio. Oscillated PU analysis revealed that 3885 genes were regulated by rhythmic RNA degradation. The RNA decay of these diurnal genes was highly coordinated with mRNA downregulation during oscillation, highlighting the critical role of internal transcription-degradation balance in rhythmic gene oscillation. Furthermore, we identified 2190 genes undergoing co-translational RNA decay (CTRD) with 5' phosphate read ends enriched at the boundary of ribosomes stalling at translational termination sites. Interestingly, diurnal-changed mRNAs with large amplitudes tended to be co-translationally decay, suggesting that CTRD contributed to the rapid turnover of diurnal mRNAs. Finally, we also identified several genes, whose miRNA cleavage efficiency oscillated in a diurnal manner. Taken together, these findings uncovered the vital functions of RNA metabolism, including rhythmic RNA degradation, CTRD, and miRNA cleavage, in modulating the diurnal mRNA oscillations during diel change at post-transcriptional level in tomato.

Application of Exogenous Ascorbic Acid Enhances Cold Tolerance in Tomato Seedlings through Molecular and Physiological Responses.

Ascorbic acid (AsA), an essential non-enzymatic antioxidant in plants, regulates development growth and responses to abiotic and biotic stresses. However, research on AsA's role in cold tolerance remains largely unknown. Here, our study uncovered the positive role of AsA in improving cold stress tolerance in tomato seedlings. Physiological analysis showed that AsA significantly enhanced the enzyme activity of the antioxidant defense system in tomato seedling leaves and increased the contents of proline, sugar, abscisic acid (ABA), and endogenous AsA. In addition, we found that AsA is able to protect the photosynthetic system of tomato seedlings, thereby relieving the declining rate of chlorophyll fluorescence parameters. qRT-PCR analysis indicated that AsA significantly increased the expression of genes encoding antioxidant enzymes and involved in AsA synthesis, ABA biosynthesis/signal transduction, and low-temperature responses in tomato. In conclusion, the application of exogenous AsA enhances cold stress tolerance in tomato seedlings through various molecular and physiological responses. This provides a theoretical foundation for exploring the regulatory mechanisms underlying cold tolerance in tomato and offers practical guidance for enhancing cold tolerance in tomato cultivation.

Fine Mapping of Candidate Gene Controlling Anthocyanin Biosynthesis for Purple Peel in Solanum melongena L.

Fruit color is an intuitive quality of horticultural crops that can be used as an evaluation criterion for fruit ripening and is an important factor affecting consumers' purchase choices. In this study, a genetic population from the cross of green peel 'Qidong' and purple peel '8 guo' revealed that the purple to green color of eggplant peel is dominant and controlled by a pair of alleles. Bulked segregant analysis (BSA), SNP haplotyping, and fine genetic mapping delimited candidate genes to a 350 kb region of eggplant chromosome 10 flanked by markers KA2381 and CA8828. One ANS gene (EGP22363) was predicted to be a candidate gene based on gene annotation and sequence alignment of the 350-kb region. Sequence analysis revealed that a single base mutation of 'T' to 'C' on the exon green peel, which caused hydrophobicity to become hydrophilic serine, led to a change in the three-level spatial structure. Additionally, EGP22363 was more highly expressed in purple peels than in green peels. Collectively, EGP22363 is a strong candidate gene for anthocyanin biosynthesis in purple eggplant peels. These results provide important information for molecular marker-assisted selection in eggplants, and a basis for analyzing the regulatory pathways responsible for anthocyanin biosynthesis in eggplants.

miR-124 Exacerbates depressive-like behavior by targeting Ezh2 to induce autophagy.

On the basis of our previous research, miR-124 and autophagy have been shown to be associated with depression and antidepressant treatment, respectively. However, whether miR-124 is involved in depressive-like behavior and antidepressant efficacy through regulating autophagy remains poorly understood. The chronic unpredictable mild stress (CUMS) depression model in mice was established, and then intraperitoneal fluoxetine injections (10 mg/kg) were administered for a duration of 4 weeks. The behavioral changes induced by CUMS were evaluated by the tail suspension test, open field test, sucrose preference test, and elevated plus maze test. Quantitative real-time PCR was used to detect expression levels of miR-124 and its three precursor genes in hippocampus of mice. Western blotting was used to detect the expressions of Ezh2 and autophagy proteins (P62, Atg3, Atg7, LC3-I, and LC3- II) in hippocampus of mice. Depression-like behaviors were successfully induced in CUMS models and reversed by SSRI treatments. The expression levels of miR-124 and its precursor gene ( miR-124-3 ) were significantly increased in the hippocampus of CUMS mice, while the expression levels were significantly decreased after 4 weeks of fluoxetine treatment. The mRNA and protein expressions of Ezh2, a validated target of miR-124, were decreased in the hippocampus of CUMS mice, and the fluoxetine treatment could reverse the expressions. A correlation analysis suggested that miR-124 had a significant negative correlation with Ezh2 mRNA expression. The protein levels of LC3-II/I, P62, and Atg7, which were found to be regulated by Ezh2, were increased in the hippocampus of CUMS mice and decreased after fluoxetine treatment. We speculated that autophagy was enhanced in the CUMS model of depression and might be mediated by miR-124 targeting Ezh2.

HiGNN: A Hierarchical Informative Graph Neural Network for Molecular Property Prediction Equipped with Feature-Wise Attention.

Elucidating and accurately predicting the druggability and bioactivities of molecules plays a pivotal role in drug design and discovery and remains an open challenge. Recently, graph neural networks (GNNs) have made remarkable advancements in graph-based molecular property prediction. However, current graph-based deep learning methods neglect the hierarchical information of molecules and the relationships between feature channels. In this study, we propose a well-designed hierarchical informative graph neural network (termed HiGNN) framework for predicting molecular property by utilizing a corepresentation learning of molecular graphs and chemically synthesizable breaking of retrosynthetically interesting chemical substructure (BRICS) fragments. Furthermore, a plug-and-play feature-wise attention block is first designed in HiGNN architecture to adaptively recalibrate atomic features after the message passing phase. Extensive experiments demonstrate that HiGNN achieves state-of-the-art predictive performance on many challenging drug discovery-associated benchmark data sets. In addition, we devise a molecule-fragment similarity mechanism to comprehensively investigate the interpretability of the HiGNN model at the subgraph level, indicating that HiGNN as a powerful deep learning tool can help chemists and pharmacists identify the key components of molecules for designing better molecules with desired properties or functions. The source code is publicly available at https://github.com/idruglab/hignn.

Correlation between the quality of cartilage repair tissue and patellofemoral osteoarthritis after matrix-induced autologous chondrocyte implantation at three-year follow-up: a cross-sectional study.

PURPOSE: To investigate whether the quality of cartilage repair tissue is associated with patellofemoral osteoarthritis (PFOA) at a three year follow-up after matrix-induced autologous chondrocyte implantation (MACI). METHODS: This retrospective study included 32 patients who underwent MACI between October 2014 and May 2018 at our institute. The Lysholm score and Visual Analog Scale (VAS) score were assessed. The magnetic resonance observation of cartilage repair tissue (MOCART) 2.0 score and T2* relaxation time of repair tissue were used to evaluate cartilage repair tissue quality. A modified MRI Osteoarthritis Knee Score (mMOAKS) was used to evaluate PFOA. RESULTS: Compared with pre-operative scores, the final Lysholm score (50.71 ± 2.22 vs 89.70 ± 1.18; t = 15.5, P < 0.0001) and VAS score (4.67 ± 0.47 vs 0.92 ± 0.64; t = 22.62, P < 0.0001) were improved at 3 years after MACI. At the three year follow-up, the mean MOCART 2.0 score was 61.56 ± 18.11, and the T2* relaxation time of the repair tissue was significantly lower than that in the healthy control region (24.11 ± 6.38 vs 34.39 ± 1.33, t = - 8.635, P < 0.0001). The mean mMOAKS score was 9.16 ± 4.51. On univariate analysis, the MOCART 2.0 score and T2* relaxation time were negatively associated with the mMOAKS score. CONCLUSION: MACI can lead to significant pain relief and restoration of knee joint function, and good quality cartilage repair tissue was a protective factor against PFOA at the three year follow-up.

Genome-Wide Analyses of SlFWL Family Genes and Their Expression Profiles under Cold, Heat, Salt and Drought Stress in Tomato.

PLAC8 is a cysteine-rich protein that serves as a central mediator of tumor evolution in mammals. PLAC8 motif-containing proteins widely distribute in fungi, algae, higher plants and animals that have been described to be implicated in fruit size, cell number and the transport of heavy metals such as cadmium or zinc. In tomatoes, FW2.2 is a PLAC8 motif-containing gene that negatively controls fruit size by regulating cell division and expansion in the carpel ovary during fruit development. However, despite FW2.2, other FWL (FW2.2-Like) genes in tomatoes have not been investigated. In this study, we identified the 21 SlFWL genes, including FW2.2, examined their expression profiles under various abiotic adversity-related conditions. The SlFWL gene structures and motif compositions are conserved, indicating that tomato SlFWL genes may have similar roles. Cis-acting element analysis revealed that the SlFWL genes may participate in light and abiotic stress responses, and they also interacted with a variety of phytohormone-responsive proteins and plant development elements. Phylogenetic analyses were performed on five additional plant species, including Arabidopsis, pepper, soybean, rice and maize, these genes were classified into five subfamilies. Based on the results of collinearity analyses, the SlFWL genes have a tighter homologous evolutionary relationship with soybean, and these orthologous FWL gene pairs might have the common ancestor. Expression profiling of SlFWL genes show that they were all responsive to abiotic stresses, each subgroup of genes exhibited a different expression trend. Our findings provide a strong foundation for investigating the function and abiotic stress responses of the SlFWL family genes.

Magnetic resonance imaging R2* sequences can better detect microstructural cartilage changes than T2 mapping in cynomolgus monkeys with limited knee kinematics: preliminary imaging findings.

BACKGROUND: The difference between MRI (Magnetic resonance imaging)-R2* and T2 mapping sequences regarding their superiority in the detection of microstructural cartilage changes in knees with limited ROM (range of motion) was unknown. METHODS: Twenty male cynomolgus monkeys (mean age: 10.65 ± 0.97 years) underwent knee ROM evaluations and were divided into three groups: Group A (n = 10), with similar left and right knee ROM; Group B (n = 5), with left knee ROM superior to right; and Group C (n = 5), with left knee ROM inferior to right. Twenty-eight ROIs (regions of interest) in the cartilage of the lateral (L) and medial (M) femoral trochlea (FT), anterior (A)/central (C)/posterior (P) femoral condyle (FC) and tibial plateau (TP) of both knees were identified in each monkey. The corresponding ROI values in R2* and T2 mapping sequences were recorded for analysis. One-way ANOVA, Chi-square tests and Pearson's correlation analysis were used for statistical analyses. RESULTS: Among the total 1120 ROIs, significant differences in R2* values among the three groups existed in two ROIs: cartilage of the right MPTP (F = 5.216, P = 0.017) and left MAFC (F = 4.919, P = 0.021). However, the T2 mapping values of all ROIs were similar among the three groups. Microstructural cartilage changes occurred more frequently in the medial (40 ROIs) than in the lateral (0 ROIs) knee compartment (χ2 = 43.077, P < 0.001). The Group B cartilage R2* value of the right MPTP increased with the difference in bilateral knee ROM (r = 0.913, P = 0.030). CONCLUSIONS: In knees with limited ROM, MRI-R2* sequence is superior to T2 mapping in the detection of microstructural cartilage changes, which the medial knee compartment was more susceptible to. Cartilage R2* values tend to increase with the amount of knee ROM loss.

Prediction Model for Severe Mycoplasma pneumoniae Pneumonia in Pediatric Patients by Admission Laboratory Indicators.

OBJECTIVE: The purpose of this study was to develop a model for predicting severe Mycoplasma pneumoniae pneumonia (SMPP) in pediatric patients with Mycoplasma pneumoniae pneumonia (MPP) on admission by laboratory indicators. METHODS: Pediatric patients with MPP from January 2019 to December 2020 in our hospital were enrolled in this study. SMPP was diagnosed according to guideline for diagnosis and treatment of community-acquired pneumonia in children (2019 version). Prediction model was developed according to the admission laboratory indicators. Receiver operating characteristic curve and Goodness-of-fit test were analyzed for the predictive value. RESULTS: A total of 233 MPP patients were included in the study, with 121 males and 112 females, aged 4.541 (1-14) years. Among them, 84 (36.1%, 95% CI 29.9-42.6%) pediatric patients were diagnosed as SMPP. Some admission laboratory indicators (immunoglobulins M (IgM), eosinophil proportion, eosinophil count, hemoglobin, erythrocyte sedimentation rate (ESR), total protein, albumin and prealbumin) were found statistically different (p < 0.05) between non-SMPP group and SMPP group. Logistic regress analysis showed IgM, eosinophil proportion, eosinophil count, ESR and prealbumin were independent risk factors for SMPP. According to these five admission laboratory indicators, the prediction model for SMPP in pediatric patients was developed. The area under curve of the prediction model was 0.777, and the goodness-of-fit test showed that the predicted SMPP incidence by the model was consistent with the actual incidence (χ2 = 244.51, p = 0.203). CONCLUSION: We developed a model for predicting SMPP in pediatric patients by admission laboratory indicators. This model has good discrimination and calibration, which provides a basis for the early identification SMPP on admission. However, this model should be validated by multicenter studies with large sample.

Effect of Exogenous Glycine Betaine on the Germination of Tomato Seeds under Cold Stress.

Cold stress is known to influence tomato growth, development, and yield. In this study, we analyzed the germination of tomato seeds treated with exogenous glycine betaine (GB) at a low temperature (14 °C). The results showed that cold stress inhibited tomato seed germination, and pretreatment with exogenous GB reduced this inhibition and enhanced the germination rate (GR), germination index (GI), and viability of tomato seeds at low temperatures. Analysis of gene expression and metabolism revealed that GB positively regulated endogenous hormone gibberellin (GA) content and negatively regulated abscisic acid (ABA) content, while GB reduced the starch content in the seeds by up-regulating the amylase gene expression. Gene expression analysis showed that the key genes (SlSOD, SlPOD, and SlchlAPX) involved in reactive oxygen species (ROS) scavenging systems were up-regulated in GB-pretreated tomato seeds compared with the control. At the same time, levels of malondialdehyde and hydrogen peroxide were significantly lower, while the proline content and peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) levels were elevated compared with those in the control. These results demonstrate that exogenous GB as a positive regulator effectively alleviated the inhibition of tomato seed germination under cold stress by different signal pathways.

Fine Mapping and Gene Analysis of restorer-of-fertility Gene CaRfHZ in Pepper (Capsicum annuum L.).

Cytoplasmic male sterility (CMS) is a common biological phenomenon used in hybrid production of peppers (Capsicum annuum L.). Although several restorer-of-fertility (Rf) genes of pepper CMS lines have been mapped, there is no report that the Rf gene with clear gene function has been isolated. Here, pepper CMS line HZ1A and its restorer line HZ1C were used to construct (HZ1A × HZ1C) F2 populations and map the Rf gene. A single dominant gene CaRfHZ conferred male fertility according to inheritance analysis. Using sterile plants from (HZ1A × HZ1C) F2 populations and bulked segregant analysis (BSA), the CaRfHZ gene was mapped between P06gInDel-66 and P06gInDel-89 on chromosome 6. This region spans 533.81 kb, where four genes are annotated according to Zunla-1 V2.0 gene models. Based on the analysis of genomic DNA sequences, gene expressions, and protein structures, Capana06g002968 was proposed as the strongest candidate for the CaRfHZ gene. Our results may help with hybrid pepper breeding and to elucidate the mechanism of male fertility restoration in peppers.

Transcriptome Analyses Reveal the Role of Light in Releasing the Morphological Dormancy of Celery Seed by Integrating Plant Hormones, Sugar Metabolism and Endosperm Weakening.

Celery seed is known to be difficult to germinate due to its morphological dormancy. Light is the key signal to release morphological dormancy and promote seed germination. However, this mechanism has rarely been studied. We performed physiological, transcriptome analyses on celery seed exposed to light and dark to decipher the mechanism by which light promotes germination of celery seed. The results showed that light significantly enhanced the expression of gibberellin synthesis genes and abscisic acid degradation genes and inhibited the expression of abscisic acid synthesis genes and gibberellin degradation genes. Moreover, gibberellin synthesis inhibitor could completely inhibit the germination capacity of celery seed, indicating that gibberellin is indispensable in the process of celery seed germination. Compared with dark, light also increased the activity of α-amylase and ß-amylase and the expression of related coding genes and promoted the degradation of starch and the increase of soluble sugar content, suggesting that light enhanced the sugar metabolism of celery seed. In addition, transcriptome analysis revealed that many genes related to endosperm weakening (cell wall remodeling enzymes, extension proteins) were up-regulated under light. It was also found that light promoted the accumulation of hydrogen peroxide in the radicle, which promoted the endosperm weakening process of celery seed. Our results thus indicated that light signal may promote the release of morphological dormancy through the simultaneous action of multiple factors.

Arthroscopic reconstruction of anterior cruciate ligaments with allograft: single-tunnel single-bundle versus single-tunnel double-bundle techniques.

PURPOSE: To compare the clinical results of anterior cruciate ligament (ACL) reconstruction using the single-tunnel single-bundle (STSB) technique versus the single-tunnel double-bundle (STDB) technique. METHODS: This was a retrospective, single-center, single-surgeon study based on data collected from March 2012 to June 2013. According to our inclusion/exclusion criteria, a total of 78 patients (64 males, 14 females; mean age, 25.1 years) who underwent arthroscopic ACL reconstruction with anterior tibialis tendon allografts through either the STSB technique (36 cases) or the STDB technique (42 cases) in our department were recruited. The International Knee Documentation Committee (IKDC), Lysholm, and Tegner scores were used to evaluate the subjective function of the knee joint during the postoperative follow-up. The Lachman test and pivot shift test were used to objectively assess the stability of the knee. RESULTS: The average follow-up duration was 24.9 ± 1.8 months in the STSB group and 24.6 ± 1.7 months in the STDB group (P > 0.05). Patients in both groups recovered to the preoperative sports level with few complications. The postoperative Lysholm score (86.1 ± 7.5 vs. 47.7 ± 9.0 in the STSB group; 87.0 ± 7.1 vs. 48.2 ± 8.3 in the STDB group), IKDC score (87.8 ± 7.2 vs. 49.3 ± 6.1 in the STSB group; 88.7 ± 6.6 vs. 49.8 ± 6.3 in the STDB group), Tegner score (6.5 ± 1.3 vs. 2.5 ± 1.3 in the STSB group; 6.6 ± 1.2 vs. 2.6 ± 1.2 in the STDB group), Lachman test positive rate (8.3% vs. 89.9% in the STSB group; 7.1% vs. 85.7% in the STDB group), and pivot shift test positive rate (27.8% vs. 63.9% in the STSB group; 7.1% vs. 69.0% in the STDB group) were significantly improved compared to the preoperative status in both groups (P < 0.05). However, no statistically significant difference was observed between the two groups at the final follow-up (P > 0.05), except for the pivot shift test positive rate in the STDB group versus the STSB group (7.1% vs. 27.8%, P < 0.05). CONCLUSIONS: The STDB technique achieved a satisfactory clinical outcome with better rotational stability compared to the traditional STSB technique and therefore provided an effective option for ACL reconstruction. LEVEL OF EVIDENCE: Case series, Level IV.

A long-wavelength activable AIEgen fluorescent probe for HClO and cell apoptosis imaging.

Hypochlorous acid (HClO) is an important bactericide, and adjusting the content of HClO helps to improve the host's innate immunity and resist microbial invasion. Aggregation-induced luminescence (AIE) is the opposite of aggregation-induced quenching (ACQ). Compounds with AIE properties emit weakly in a dispersed state in solution and they can emit strong fluorescence in an aggregated state. In this article, we proposed a new AIE fluorescent probe QM-ClO based on the quinoline-malononitrile (QM) fluorophore and dimethylthiocarbamate (DMTC) to detect HClO. The probe QM-ClO showed a fast response time, a low detection limit of 30.8 nM and a large Stokes shift (190 nm). Carbonyl cyanide metachlorophenyl-hydrazone (CCCP) was used to induce cell apoptosis, and then an increase in the HClO content was observed in the cell. It is proved that cell apoptosis can lead to the increase of the HClO content in the cell. This probe provides an effective tool for studying apoptosis-related diseases.

Correlation between the subchondral bone marrow lesions and cartilage repair tissue after matrix-associated autologous chondrocyte implantation in the knee: a cross-sectional study.

BACKGROUND: The contribution of the subchondral bone in the development and progression of osteoarthritis (OA) has long been recognized, but its role in cartilage repair procedures has only recently attracted more attention. PURPOSE: To explore the correlation between the cartilage repair tissue (RT) and the subchondral bone marrow lesions (BMLs) after matrix-associated autologous chondrocyte implantation (MACI) in the knee joint. MATERIAL AND METHODS: A total of 30 patients who underwent MACI in the knee from January 2015 to June 2018 and follow-up magnetic resonance imaging (MRI) scan were recruited in this study. The MRI results of cartilage RT were evaluated using T2* relaxation time. Subchondral BMLs were also qualitatively evaluated by use of the two-dimensional proton density-weighted fat-suppressed (2D-PD-FS) and three-dimensional dual-echo steady-state (3D-DESS) sequences. RESULTS: The univariate analysis displayed a significant negative correlation between subchondral BMLs and cartilage RT (P < 0.01). In the minimally adjusted model (only age, sex, and body mass index [BMI] adjusted), the results did not show obvious changes (ß = -6.54, 95% confidence interval [CI] = -10.99 to -2.09; P = 0.008). After adjustment for the full models (age, sex, BMI, defect size, combined injury, and preoperative duration of symptoms adjusted), the connection was also detected (ß = -6.66, 95% CI -11.82 to -1.50; P = 0.019). CONCLUSION: After MACI, the subchondral BMLs are significantly correlated with cartilage RT-T2* relaxation time. The role of subchondral bone in cartilage repair procedures should not be underestimated.

Preliminary Study on the Safety and Efficacy of One-Stop Treatment of Percutaneous LAAO Combined with Coronary Intervention for Higher Risk of Bleeding in Patients with AF Complicated with CHD.

AIMS: To explore the feasibility, safety, and efficacy of 1-stop treatment of percutaneous left atrial appendage occlusion (LAAO) combined with coronary intervention for patients with nonvalvular atrial fibrillation (AF) complicated with coronary heart disease (CHD). METHODS AND RESULTS: We retrospectively analyzed the clinical data of 6 patients with AF combined with CHD admitted from Zhuhai People's Hospital from April 2017 to June 2018. After the operation, all patients were treated with aspirin (100 mg qd) and clopidogrel (75 mg qd) for 1 year, which is considered long-term use of aspirin/clopidogrel. The effects of LAAO and coronary intervention were evaluated immediately. The location of the left atrial appendage occluder, thrombosis, residual leak, and clinical manifestations were observed during the 90-day follow-up. The patients were implanted with Watchman™ devices and coronary stents. After the operation, the immediate sealing effect was satisfactory. The Watchman occluder was used in accordance with the PASS principle (position, anchor, size, seal), and the coronary intervention was satisfactory. During the operation, there were no device-related thrombosis, tamponade, or vascular complications. Follow-up results showed that in the 6 patients, there were no hemorrhagic strokes, worsening heart function, residual leakage, device-related thrombosis, angina pectoris, myocardial infarction, skin ecchymosis, gastrointestinal bleeding, or cerebral hemorrhage. CONCLUSION: For patients with nonvalvular AF combined with CHD, the safety and feasibility of 1-stop treatment with left atrial appendage and coronary intervention are reliable, and the curative effects were also satisfactory at short- and medium-term follow-up.

Arthroscopic repair of the medium-size rotator cuff tear with the novel technique of the point union bridge: a minimum 2-year follow-up cohort study.

BACKGROUND: Achieving secure fixation and preventing retear have been recognized as fundamental in arthroscopic repair of rotator cuff tears. Moreover, reducing internal implantation can lower medical expenses and minimize the operation time, which is essential for the surgical safety and postoperative rehabilitation of the patients. We have recently proposed the point union bridge (PUB) suture configuration as a novel method for not only providing equivalent fixation but also decreasing the operation time and medical expenses. However, no comparative clinical studies have been performed. METHODS: From March 2014 to September 2016, a total of 88 patients with diagnoses of medium-size rotator cuff tears underwent arthroscopic repair with a randomly assigned technique-either the PUB technique (n = 42) or the double-row suture bridge (DRSB) technique (n = 46). All patients underwent a minimal 2-year follow-up. We used the Constant-Murley score (CMS), American Shoulder and Elbow Surgeons (ASES) score, active and passive range of motion, and visual pain-simulation score (visual analog scale [VAS] score) to assess the functional outcomes. In addition, we recorded the arthroscopic operation time, medical costs, and postoperative complications. All patients received magnetic resonance imaging at the 6-month and 2-year postoperative evaluations to assess structural integrity and tendon healing. RESULTS: At the 2-year follow-up, all scoring parameters evaluated (CMS, ASES score, and VAS score), as well as active and passive range of motion, improved significantly in both groups as compared with preoperative assessments. The PUB technique significantly decreased the operation time (55.9 ± 14.1 minutes vs. 72.2 ± 14.2 minutes for PUB vs. DRSB, P < .001) and medical expenses ($2608.0 ± $391.1 vs. $4056.9 ± $350.9 for PUB vs. DRSB, P < .001). However, no significant differences between the 2 techniques were found in any functional assessments of the shoulder (CMS, ASES score, and VAS score), repair integrity, or the retear rate at the 2-year follow-up. CONCLUSION: Arthroscopic repair of the medium-size rotator cuff tear with either the PUB or DRSB technique could yield both satisfactory improvements in the shoulder function of patients and equivalent tendon integrity. With less consumption of internal implants, the PUB technique significantly reduced the operation time and decreased medical expenses.

General method for complex-wave fields registration with high fidelity.

In the field of optical imaging, the image registration method could be applied to realize a large field of view along with high resolution. The traditional image registration methods are mostly conceived for intensity images and might fail for complex-valued images. Especially, those methods do not account for the random phase offset associated with phase. In this paper, we proposed a general method for complex-wave field registration. A similar procedure has been proposed for the reconstruction of the ptychographic dataset, but here is modified for the registration of general wave fields. The method can efficiently separate the illumination and object function, refine the positions of each wavefront, and thus provide a stitched wide-field object wave with high fidelity. Simulation and experimental results applied to register the wave fields obtained from digital holographic microscopy are given to verify the feasibility of the method. This method would have potential applications in large-field high-resolution microscopy, adaptive imaging, remote sensing and the measurement of structured optical fields.

Intra-articular injection of hUC-MSCs expressing miR-140-5p induces cartilage self-repairing in the rat osteoarthritis.

INTRODUCTION: Currently, osteoarthritis (OA) receives global increasing attention because it associates severe joint pain and serious disability. Stem cells intra-articular injection therapy showed a potential therapeutic superiority to reduce OA development and to improve treating outputs. However, the long-term effect of stem cells intra-articular injection on the cartilage regeneration remains unclear. Recently, miR-140-5p was confirmed as a critical positive regulator in chondrogenesis. We hypothesized that hUC-MSCs overexpressing miR-140-5p have better therapeutic effect on osteoarthritis. MATERIALS AND METHODS: To enhance stem cell chondrogenic differentiation, we have transfected human umbilical cord mesenchymal stem cells (hUC-MSCs) with miR-140-5p mimics and miR-140-5p lentivirus to overexpress miR-140-5p in a short term or a long term accordingly. Thereafter, MSCs proliferation, chondrogenic genes expression and extracellular matrix were assessed. Destabilization of the medial meniscus (DMM) surgery was performed on the knee joints of SD rats as an OA model, and then intra-articular injection of hUC-MSCs or hUC-MSCs transfected with miR-140-5p lentivirus was carried to evaluate the cartilage healing effect with histological staining and OARSI scores. The localization of hUC-MSCs after intra-articular injection was further confirmed by immunohistochemical staining. RESULTS: Significant induction of chondrogenic differentiation in the miR-140-5p-hUC-MSCs (140-MSCs), while its proliferation was not influenced. Interestingly, intra-articular injection of 140-MSCs significantly enhanced articular cartilage self-repairing in comparison to normal hUC-MSCs. Moreover, we noticed that intra-articular injection of high 140-MSCs numbers reinforces cells assembling on the impaired cartilage surface and subsequently differentiated into chondrocytes. CONCLUSIONS: In conclusion, these results indicate therapeutic superiority of hUC-MSCs overexpressing miR-140-5p to treat OA using intra-articular injection.