A novel method combining gated SPECT and vectorcardiography to guide left ventricular lead placement to improve response to cardiac resynchronization therapy: A Proof of Concept study.

BACKGROUND: The segment of the latest mechanical contraction (LMC) does not always overlap with the site of the latest electrical activation (LEA). By integrating both mechanical and electrical dyssynchrony, this proof-of-concept study aimed to propose a new method for recommending left ventricular (LV) lead placements, with the goal of enhancing response to cardiac resynchronization therapy (CRT). METHODS: The LMC segment was determined by single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) phase analysis. The LEA site was detected by vectorcardiogram. The recommended segments for LV lead placement were as follows: (1) the LMC viable segments that overlapped with the LEA site;(2) the LMC viable segments adjacent to the LEA site;(3) If no segment met either of the above, the LV lateral wall was recommended. The response was defined as ≥15% reduction in left ventricular end-systolic volume (LVESV) 6-months after CRT. Patients with LV lead located in the recommended site were assigned to the recommended group, and those located in the non-recommended site were assigned to the non-recommended group. RESULTS: The cohort comprised of 76 patients, including 54 (71.1%) in the recommended group and 22 (28.9%) in the non-recommended group. Among the recommended group, 74.1% of the patients responded to CRT, while 36.4% in the non-recommended group were responders (p=.002). Compared to pacing at the non-recommended segments, pacing at the recommended segments showed an independent association with an increased response by univariate and multivariable analysis (odds ratio 5.00, 95% confidence interval 1.73-14.44, p=.003; odds ratio 7.33, 95% confidence interval 1.53-35.14, p=.013). Kaplan-Meier curves showed that pacing at the recommended LV lead position demonstrated a better long-term prognosis. CONCLUSIONS: Our findings indicate that pacing at the recommended segments, by integrating of mechanical and electrical dyssynchrony, is significantly associated with an improved CRT response and better long-term prognosis.

Efficacy of Lenvatinib Combined with PD-1 Inhibitor versus Sorafenib and PD-1 Inhibitor with or Without TACE for Hepatocellular Carcinoma with Extrahepatic Metastasis.

Background: Lenvatinib or Sorafenib combined with programmed cell death protein-1 (PD-1) inhibitor as recommend treatment of advanced hepatocellular carcinoma (HCC) with extrahepatic metastasis (EHM). We aimed to compared the prognosis of Lenvatinib plus PD-1 inhibitor (Len+PD-1) versus Sorafenib plus PD-1 (Sora+PD-1) as an initial therapy for HCC with EHM. Methods: Incorporating a sum of 229 HCC patients with EHM were encompassed within this study, with 127 in the Sora+PD-1 group and 102 in the Len+PD-1 group. Through propensity score matching (PSM), we compared overall survival (OS), progression-free survival (PFS), and patient safety between these two groups. Results: The median OS were 13.0 months and 14.2 months in the Sora+PD-1 group and Len+PD-1 group. The 6-, 12-, and 24-month OS rates were 92.9%, 58.9% and 5.6% in Sora+PD-1 group and 93.1%, 61.8% and 22.6% in Len+PD-1 group, respectively. The Len+PD-1 group had obviously better OS than the Sora+PD-1 group (P = 0.002). The 3-, 6-, and 12-month PFS rates were 76.4%, 27.6% and 1.6% in Sora+PD-1 group and 86.2%, 50.5% and 12.2% in Len+PD-1 group, respectively. Compared with Sora+PD-1 group, the Len+PD-1 group had obviously better PFS (P < 0.001). Analysis within subgroups showed that OS was significant in patients receiving TACE in Len+PD-1 group than Sora+PD-1 group (p = 0.003). Conclusion: Len+PD-1 group had longer OS and PFS than Sora+PD-1 group for patient with EHM. In addition, OS in patients received TACE was improved with Len+PD-1 treatment. For patients without TACE, there was no significance between Sora+PD-1 and Len+PD-1 groups.

Carbon emission reduction enabled by informatization construction: an analysis of spatial effects based on China's experience.

The "dual-carbon" objective presents a huge challenge for China and the world, with profound implications for the advancement of China's eco-friendly economy. Additionally, informatization development has a significant impact on the level of carbon emissions in both local and neighbouring regions. Therefore, we employ panel data from 30 provinces in China spanning the years 2012 to 2021, and use the Kernel density estimate and Moran's index to explore informatization level and carbon emissions space agglomeration characteristics. We elucidate the nonlinear relationship and heterogeneity between informatization improvement and carbon emissions based on the spatial Durbin model. The primary findings are as follows. Firstly, we discover a distinct spatial clustering phenomenon which the informatization level is high in coastal areas and low in inland areas, whereas carbon emissions are low in the south and high in the north. Secondly, the effect of the informatization level on carbon emissions is shown as a U-shaped and non-linear correlation, signifying inhibitory and subsequently promoting phases. Thirdly, we reveal the negative influence on carbon emissions caused by spatial lag terms of the informatization level, and find that a higher local informatization level will have an inhibitory effect on carbon emissions in neighbouring areas. Finally, there is a spatial heterogeneity in the impact of the informatization level on carbon emissions, which presents the U-shaped relation between informatization level and carbon emissions varies across the North-South subregion and the three major economic subregion of China.

SKP alleviates the ferroptosis in diabetic kidney disease through suppression of HIF-1α/HO-1 pathway based on network pharmacology analysis and experimental validation.

BACKGROUND: Diabetic kidney disease (DKD) represents a microvascular complication of diabetes mellitus. Shenkang Pills (SKP), a traditional Chinese medicine formula, has been widely used in the treatment of DKD and has obvious antioxidant effect. Ferroptosis, a novel mode of cell death due to iron overload, has been shown to be associated with DKD. Nevertheless, the precise effects and underlying mechanisms of SKP on ferroptosis in diabetic kidney disease remain unclear. METHODS: The active components of SKP were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Protein-protein interaction (PPI) network and Herb-ingredient-targets gene network were constructed using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted utilizing the Metascape system database. Additionally, an in vivo model of DKD induced by Streptozotocin (STZ) was established to further investigate and validate the possible mechanisms underlying the effectiveness of SKP. RESULTS: We retrieved 56 compounds and identified 223 targets of SKP through the TCMSP database. Key targets were ascertained using PPI network analysis. By constructing a Herb-Ingredient-Targets gene network, we isolated the primary active components in SKP that potentially counteract ferroptosis in diabetic kidney disease. KEGG pathway enrichment analysis suggested that SKP has the potential to alleviate ferroptosis through HIF signaling pathway, thereby mitigating renal injury in DKD. In animal experiments, fasting blood glucose, 24 h urine protein, urea nitrogen and serum creatine were measured. The results showed that SKP could improve DKD. Results from animal experiments were also confirmed the efficacy of SKP in alleviating renal fibrosis, oxidative stress and ferroptosis in DKD mice. These effects were accompanied by the significant reductions in renal tissue expression of HIF-1α and HO-1 proteins. The mRNA and immunohistochemistry results were the same as above. CONCLUSIONS: SKP potentially mitigating renal injury in DKD by subduing ferroptosis through the intricacies of the HIF-1α/HO-1 signaling pathway.

Helicobacter pylori CagA promotes immune evasion of gastric cancer by upregulating PD-L1 level in exosomes.

Cytotoxin-associated gene A (CagA) of Helicobacter pylori (Hp) may promote immune evasion of Hp-infected gastric cancer (GC), but potential mechanisms are still under explored. In this study, the positive rates of CagA and PD-L1 protein in tumor tissues and the high level of exosomal PD-L1 protein in plasma exosomes were significantly associated with the elevated stages of tumor node metastasis (TNM) in Hp-infected GC. Moreover, the positive rate of CagA was positively correlated with the positive rate of PD-L1 in tumor tissues and the level of PD-L1 protein in plasma exosomes, and high level of exosomal PD-L1 might indicate poor prognosis of Hp-infected GC. Mechanically, CagA increased PD-L1 level in exosomes derived from GC cells by inhibiting p53 and miRNA-34a, suppressing proliferation and anticancer effect of CD8+ T cells. This study provides sights for understanding immune evasion mediated by PD-L1. Targeting CagA and exosomal PD-L1 may improve immunotherapy efficacy of Hp-infected GC.

Organocatalytic Diastereoselective (4 + 1) Cycloaddition of o-Hydroxyphenyl-Substituted Secondary Phosphine Oxides.

The first organocatalytic diastereoselective (4 + 1) cycloaddition of o-hydroxyphenyl-substituted secondary phosphine oxides (SPOs) has been established, which makes use of o-hydroxyphenyl substituted SPOs as suitable four-atom phosphorus-containing 1,4-dinucleophiles and 3-indolylformaldehydes as competent 1,1-dielectrophiles under BroÌ·nsted acid catalysis. The reaction mechanism was suggested to involve the formation of 3-indolylmethanol intermediates and vinyliminium intermediates, which played an important role in controlling the reactivity and diastereoselectivity of the (4 + 1) cycloaddition under BroÌ·nsted acid catalysis. By this approach, a series of benzo oxaphospholes bearing P- and C-stereocenters were synthesized in moderate to good yields (50%-95% yields) with excellent diastereoselectivities (all >95:5 dr). This reaction not only represents the first organocatalytic diastereoselective (4 + 1) cycloaddition of o-hydroxyphenyl-substituted SPOs but also provides an efficient and diastereoselective method for the construction of phosphorus-containing benzo five-membered heterocyclic skeletons bearing both P-stereocenter and C-stereocenter.

Spatial-temporal V-Net for automatic segmentation and quantification of right ventricle on gated myocardial perfusion SPECT images.

BACKGROUND: Functional assessment of right ventricle (RV) using gated myocardial perfusion single-photon emission computed tomography (MPS) heavily relies on the precise extraction of right ventricular contours. PURPOSE: In this paper, we present a new deep-learning-based model integrating both the spatial and temporal features in gated MPS images to perform the segmentation of the RV epicardium and endocardium. METHODS: By integrating the spatial features from each cardiac frame of the gated MPS and the temporal features from the sequential cardiac frames of the gated MPS, we developed a Spatial-Temporal V-Net (ST-VNet) for automatic extraction of RV endocardial and epicardial contours. In the ST-VNet, a V-Net is employed to hierarchically extract spatial features, and convolutional long-term short-term memory (ConvLSTM) units are added to the skip-connection pathway to extract the temporal features. The input of the ST-VNet is ECG-gated sequential frames of the MPS images and the output is the probability map of the epicardial or endocardial masks. A Dice similarity coefficient (DSC) loss which penalizes the discrepancy between the model prediction and the manual annotation was adopted to optimize the segmentation model. RESULTS: Our segmentation model was trained and validated on a retrospective dataset with 45 subjects, and the cardiac cycle of each subject was divided into eight gates. The proposed ST-VNet achieved a DSC of 0.8914 and 0.8157 for the RV epicardium and endocardium segmentation, respectively. The mean absolute error, the mean squared error, and the Pearson correlation coefficient of the RV ejection fraction (RVEF) between the manual annotation and the model prediction were 0.0609, 0.0830, and 0.6985. CONCLUSION: Our proposed ST-VNet is an effective model for RV segmentation. It has great promise for clinical use in RV functional assessment.

Association between Dietary Inflammatory Index and Risk of Colorectal Adenomatous Polyps in Kashgar Prefecture of Xinjiang, China.

Malignant colorectal tumors and precancerous lesions are closely associated with chronic inflammation. Specific dietary patterns can increase chronic inflammation in the body, thereby promoting the occurrence of tumors and precancerous lesions. We have conducted a case-control study in Kashgar Prefecture, Xinjiang, China, to explore the association between the energy-adjusted dietary inflammatory index (E-DII) and the risk of colorectal adenomatous polyps (CAP). A total of 52 newly diagnosed patients with CAP and 192 controls at the First People's Hospital of Kashgar Prefecture were enrolled in this study. Dietary information was collected using a food frequency questionnaire. The E-DII was calculated based on dietary data, reflecting an individual's dietary inflammatory potential. Logistic regression models were used to evaluate the relationship between the E-DII and the risk of CAP, with adjustments for potential confounding factors. The results showed that the maximum anti- and pro-inflammatory values of E-DII were -4.33 and +3.48, respectively. Higher E-DII scores were associated with an increased risk of CAP, and this association remained statistically significant after adjusting for age, sex, body mass index, smoking status, and other relevant variables. Notably, a more pro-inflammatory dietary pattern may be related to an increased risk of developing CAP in Kashgar Prefecture.

Regulation of Tomato Fruit Autophagic Flux and Promotion of Fruit Ripening by the Autophagy-Related Gene SlATG8f.

Autophagy is a highly conserved self-degradation process that involves the degradation and recycling of cellular components and organelles. Although the involvement of autophagy in metabolic changes during fruit ripening has been preliminarily demonstrated, the variations in autophagic flux and specific functional roles in tomato fruit ripening remain to be elucidated. In this study, we analyzed the variations in autophagic flux during tomato fruit ripening. The results revealed differential expression of the SlATG8 family members during tomato fruit ripening. Transmission electron microscopy observations and dansylcadaverine (MDC) staining confirmed the presence of autophagy at the cellular level in tomato fruits. Furthermore, the overexpression of SlATG8f induced the formation of autophagosomes, increased autophagic flux within tomato fruits, and effectively enhanced the expression of ATG8 proteins during the color-transition phase of fruit ripening, thus promoting tomato fruit maturation. SlATG8f overexpression also led to the accumulation of vitamin C (VC) and soluble solids while reducing acidity in the fruit. Collectively, our findings highlight the pivotal role of SlATG8f in enhancing tomato fruit ripening, providing insights into the mechanistic involvement of autophagy in this process. This research contributes to a better understanding of the key factors that regulate tomato fruit quality and offers a theoretical basis for tomato variety improvement.

A machine learning method integrating ECG and gated SPECT for cardiac resynchronization therapy decision support.

PURPOSE: Cardiac resynchronization therapy (CRT) has been established as an important therapy for heart failure. Mechanical dyssynchrony has the potential to predict responders to CRT. The aim of this study was to report the development and the validation of machine learning models which integrate ECG, gated SPECT MPI (GMPS), and clinical variables to predict patients' response to CRT. METHODS: This analysis included 153 patients who met criteria for CRT from a prospective cohort study. The variables were used to model predictive methods for CRT. Patients were classified as "responders" for an increase of LVEF ≥ 5% at follow-up. In a second analysis, patients were classified as "super-responders" for an increase of LVEF ≥ 15%. For ML, variable selection was applied, and Prediction Analysis of Microarrays (PAM) approach was used to model response while Naïve Bayes (NB) was used to model super-response. These ML models were compared to models obtained with guideline variables. RESULTS: PAM had AUC of 0.80 against 0.72 of partial least squares-discriminant analysis with guideline variables (p = 0.52). The sensitivity (0.86) and specificity (0.75) were better than for guideline alone, sensitivity (0.75) and specificity (0.24). Neural network with guideline variables was better than NB (AUC = 0.93 vs. 0.87) however without statistical significance (p = 0.48). Its sensitivity and specificity (1.0 and 0.75, respectively) were better than guideline alone (0.78 and 0.25, respectively). CONCLUSIONS: Compared to guideline criteria, ML methods trended toward improved CRT response and super-response prediction. GMPS was central in the acquisition of most parameters. Further studies are needed to validate the models.

Protein Kinase D1 Correlates with Less Lymph Node Metastasis Risk, Enhanced 5-FU Sensitivity, and Better Prognosis in Colorectal Cancer.

Protein kinase D1 (PKD1) controls tumor growth and invasion of gastrointestinal tract-related cancers, but its prognostic role in colorectal cancer (CRC) is not clear yet. Therefore, this research intended to assess the potential of PKD1 as a marker for CRC patients' management, also to evaluate its effect on 5-fluorouracil (5-FU) chemosensitivity in CRC cell lines. PKD1 protein and mRNA expressions were measured by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction assays in 214 CRC patients, respectively. The PKD1 overexpression plasmids and negative control (NC) plasmids were transfected into the HCT-116 and LoVo cell lines followed by 0-16 µM 5-FU treatment. PKD1 protein (P < 0.001) and mRNA expressions (P < 0.001) were both descended in tumor tissues compared to tumor-adjacent tissues. Meanwhile, tumor PKD1 protein and mRNA expressions were both negatively related to lymph node metastasis, N stage, and tumor-node-metastasis (TNM) stage (all P < 0.05). Prognostically, high expressions of PKD1 protein and mRNA were linked with prolonged disease-free survival (DFS) and overall survival (OS) (all P < 0.05). After adjustment by multivariate Cox analyses, PKD1 mRNA high expression independently forecasted longer DFS [hazard ratio (HR) = 0.199, P = 0.002] and OS (HR = 0.212, P = 0.022). In vitro experiments revealed that PKD1 overexpression decreased the half maximal inhibitory concentration value of 5-FU in the HCT-116 (P = 0.016) and LoVo (P = 0.007) cell lines. PKD1 expression links with less lymph node metastasis risk and satisfied prognosis in CRC patients, which promotes CRC cell chemosensitivity to 5-FU chemosensitivity as well.

Discovery of Novel Benzoxaborole-Containing Streptochlorin Derivatives as Potential Antifungal Agents.

Streptochlorin is a kind of indole alkaloid derived from marine microorganisms. It is a promising lead compound due to its potent bioactivity in preventing many phytopathogens, as shown in our previous study. To explore the potential applications of this natural product, a series of novel benzoxaborole-containing streptochlorin derivatives were designed and synthesized through a one-step and catalyst-free reaction in water at room temperature. All target compounds were first screened for their antifungal profiles in vitro against six common phytopathogenic fungi. The results of bioassay revealed that most of the designed compounds exhibited more significant antifungal activities against Botrytis cinrea, Gibberella zeae, Rhizoctorzia solani, Colletotrichum lagenarium, and alternaria leaf spot under the concentration of 50 µg/mL, and this is highlighted by compounds 4i and 5f, which demonstrated impressive antifungal effects against G. zeae and R. solani, with their corresponding EC50 values 0.2983 and 0.2657 µg/mL, which are obviously better than positive control flutriafol and boscalid (5.2606 and 1.2048 µg/mL, respectively). Scanning electron microscopy on the hyphae morphology showed that compound 5b might cause mycelial abnormalities of G. zeae. 3D-QSAR studies of CoMFA and CoMSIA were carried out on 29 target compounds with antifungal activity against B. cinrea. The analysis results indicated that introducing appropriate electronegative groups at the 5-position of benzoxaborole and the 4,5-positions of the indole ring could effectively improve the anti-B. cinrea activity. Moreover, compound 5b showed good antifungal activities in vivo against Phytophthora capsici. Molecular docking was further explored to ascertain the practical value of the active compound as a potential inhibitor of LeuRS. The abovementioned results indicate that the designed benzoxaborole-containing streptochlorin derivatives could be further studied as template molecules of novel antifungal agents.

Feasibility of Left Ventricle Lead Implantation in Cardiac Resynchronization Therapy Guided by Gated SPECT and Ventricular Remodeling. / Viabilidade do Implante de Eletrodo Ventricular Esquerdo na Terapia de Ressincronização Cardíaca Guiada por Gated SPECT e Remodelamento Ventricular.

BACKGROUND: Cardiac resynchronization therapy (CRT) may benefit patients with advanced heart failure (HF). Abnormal eccentricity index by gated SPECT is related to structural and functional alterations of the left ventricle (LV). OBJECTIVE: The aim of this study is to evaluate the feasibility of LV lead implantation guided by phase analysis and its relationship to ventricular remodeling. METHODS: Eighteen patients with indication for CRT underwent myocardial scintigraphy for implant orientation, and eccentricity and ventricular shape parameters were evaluated. P < 0.05 was adopted as statistical significance. RESULTS: At baseline, most patients were classified as NYHA 3 (n = 12). After CRT, 11 out of 18 patients were reclassified to a lower degree of functional limitation. In addition, patients' quality of life was improved post-CRT. Significant reductions were observed in QRS duration, PR interval, end-diastolic shape index, end-systolic shape index, stroke volume, and myocardial mass post-CRT. The CRT LV lead was positioned concordant, adjacent, and discordant in 11 (61.1%), 5 (27.8%), and 2 (11.1%) patients, respectively. End-systolic and end-diastolic eccentricity demonstrated reverse remodeling post-CRT. CONCLUSIONS: LV lead implantation in CRT guided by gated SPECT scintigraphy is feasible. The placement of the electrode concordant or adjacent to the last segment to contract was a determinant of reverse remodeling.

FUNDAMENTO: A terapia de ressincronização cardíaca (TRC) pode beneficiar pacientes com insuficiência cardíaca (IC) avançada. O índice de excentricidade anormal por gated SPECT está relacionado a alterações estruturais e funcionais do ventrículo esquerdo (VE). OBJETIVO: O objetivo do presente estudo foi avaliar a viabilidade do implante de eletrodos do VE guiado por análise de fase e sua relação com o remodelamento ventricular. MÉTODOS: Dezoito pacientes com indicação de TRC foram submetidos à cintilografia miocárdica para orientar o implante, avaliando-se os parâmetros de excentricidade e forma ventricular. P < 0,05 foi adotado como significância estatística. RESULTADOS: Na linha de base do estudo, a maioria dos pacientes foi classificada como NYHA 3 (n = 12). Após a TRC, 11 dos 18 pacientes foram reclassificados para um menor grau de limitação funcional. Além disso, a qualidade de vida dos pacientes melhorou após a TRC. Foram observadas reduções significativas na duração do QRS, intervalo PR, índice de forma diastólica final, índice de forma sistólica final, volume sistólico e massa miocárdica pós-TRC. O eletrodo do VE da TRC foi posicionado concordante, adjacente e discordante em 11 (61,1%), 5 (27,8%) e 2 (11,1%) pacientes, respectivamente. A excentricidade sistólica e diastólica final demonstrou remodelamento reverso após a TRC. CONCLUSÕES: O implante de eletrodo do VE em TRC guiado por cintilografia gated SPECT é viável. A colocação do eletrodo concordante ou adjacente ao último segmento a se contrair foi um determinante do remodelamento reverso.

Automatic reorientation by deep learning to generate short-axis SPECT myocardial perfusion images.

BACKGROUND: Single photon emission computed tomography (SPECT) myocardial perfusion images (MPI) can be displayed both in traditional short-axis (SA) cardiac planes and polar maps for interpretation and quantification. It is essential to reorient the reconstructed transaxial SPECT MPI into standard SA slices. This study is aimed to develop a deep-learning-based approach for automatic reorientation of MPI. METHODS: A total of 254 patients were enrolled, including 226 stress SPECT MPIs and 247 rest SPECT MPIs. Fivefold cross-validation with 180 stress and 201 rest MPIs was used for training and internal validation; the remaining images were used for testing. The rigid transformation parameters (translation and rotation) from manual reorientation were annotated by an experienced nuclear cardiologist and used as the reference standard. A convolutional neural network (CNN) was designed to predict the transformation parameters. Then, the derived transform was applied to the grid generator and sampler in spatial transformer network (STN) to generate the reoriented image. A loss function containing mean absolute errors for translation and mean square errors for rotation was employed. A three-stage optimization strategy was adopted for model optimization: (1) optimize the translation parameters while fixing the rotation parameters; (2) optimize rotation parameters while fixing the translation parameters; (3) optimize both translation and rotation parameters together. RESULTS: In the test set, the Spearman determination coefficients of the translation distances and rotation angles between the model prediction and the reference standard were 0.993 in X axis, 0.992 in Y axis, 0.994 in Z axis, 0.987 along X axis, 0.990 along Y axis and 0.996 along Z axis, respectively. For the 46 stress MPIs in the test set, the Spearman determination coefficients were 0.858 in percentage of profusion defect (PPD) and 0.858 in summed stress score (SSS); for the 46 rest MPIs in the test set, the Spearman determination coefficients were 0.9 in PPD and 0.9 in summed rest score (SRS). CONCLUSIONS: Our deep learning-based LV reorientation method is able to accurately generate the SA images. Technical validations and subsequent evaluations of measured clinical parameters show that it has great promise for clinical use.

A method using deep learning to discover new predictors from left-ventricular mechanical dyssynchrony for CRT response.

BACKGROUND: Studies have shown that the conventional parameters characterizing left ventricular mechanical dyssynchrony (LVMD) measured on gated SPECT myocardial perfusion imaging (MPI) have their own statistical limitations in predicting cardiac resynchronization therapy (CRT) response. The purpose of this study is to discover new predictors from the polarmaps of LVMD by deep learning to help select heart failure patients with a high likelihood of response to CRT. METHODS: One hundred and fifty-seven patients who underwent rest gated SPECT MPI were enrolled in this study. CRT response was defined as an increase in left ventricular ejection fraction (LVEF) > 5% at 6 [Formula: see text] 1 month follow up. The autoencoder (AE) technique, an unsupervised deep learning method, was applied to the polarmaps of LVMD to extract new predictors characterizing LVMD. Pearson correlation analysis was used to explain the relationships between new predictors and existing clinical parameters. Patients from the IAEA VISION-CRT trial were used for an external validation. Heatmaps were used to interpret the AE-extracted feature. RESULTS: Complete data were obtained in 130 patients, and 68.5% of them were classified as CRT responders. After variable selection by feature importance ranking and correlation analysis, one AE-extracted LVMD predictor was included in the statistical analysis. This new AE-extracted LVMD predictor showed statistical significance in the univariate (OR 2.00, P = .026) and multivariate (OR 1.11, P = .021) analyses, respectively. Moreover, the new AE-extracted LVMD predictor not only had incremental value over PBW and significant clinical variables, including QRS duration and left ventricular end-systolic volume (AUC 0.74 vs 0.72, LH 7.33, P = .007), but also showed encouraging predictive value in the 165 patients from the IAEA VISION-CRT trial (P < .1). The heatmaps for calculation of the AE-extracted predictor showed higher weights on the anterior, lateral, and inferior myocardial walls, which are recommended as LV pacing sites in clinical practice. CONCLUSIONS: AE techniques have significant value in the discovery of new clinical predictors. The new AE-extracted LVMD predictor extracted from the baseline gated SPECT MPI has the potential to improve the prediction of CRT response.

Viabilidade do Implante de Eletrodo Ventricular Esquerdo na Terapia de Ressincronização Cardíaca Guiada por Gated SPECT e Remodelamento Ventricular / Feasibility of Left Ventricle Lead Implantation in Cardiac Resynchronization Therapy Guided by Gated SPECT and Ventricular Remodeling

Resumo Fundamento A terapia de ressincronização cardíaca (TRC) pode beneficiar pacientes com insuficiência cardíaca (IC) avançada. O índice de excentricidade anormal por gated SPECT está relacionado a alterações estruturais e funcionais do ventrículo esquerdo (VE). Objetivo O objetivo do presente estudo foi avaliar a viabilidade do implante de eletrodos do VE guiado por análise de fase e sua relação com o remodelamento ventricular. Métodos Dezoito pacientes com indicação de TRC foram submetidos à cintilografia miocárdica para orientar o implante, avaliando-se os parâmetros de excentricidade e forma ventricular. P < 0,05 foi adotado como significância estatística. Resultados Na linha de base do estudo, a maioria dos pacientes foi classificada como NYHA 3 (n = 12). Após a TRC, 11 dos 18 pacientes foram reclassificados para um menor grau de limitação funcional. Além disso, a qualidade de vida dos pacientes melhorou após a TRC. Foram observadas reduções significativas na duração do QRS, intervalo PR, índice de forma diastólica final, índice de forma sistólica final, volume sistólico e massa miocárdica pós-TRC. O eletrodo do VE da TRC foi posicionado concordante, adjacente e discordante em 11 (61,1%), 5 (27,8%) e 2 (11,1%) pacientes, respectivamente. A excentricidade sistólica e diastólica final demonstrou remodelamento reverso após a TRC. Conclusões O implante de eletrodo do VE em TRC guiado por cintilografia gated SPECT é viável. A colocação do eletrodo concordante ou adjacente ao último segmento a se contrair foi um determinante do remodelamento reverso.

Abstract Background Cardiac resynchronization therapy (CRT) may benefit patients with advanced heart failure (HF). Abnormal eccentricity index by gated SPECT is related to structural and functional alterations of the left ventricle (LV). Objective The aim of this study is to evaluate the feasibility of LV lead implantation guided by phase analysis and its relationship to ventricular remodeling. Methods Eighteen patients with indication for CRT underwent myocardial scintigraphy for implant orientation, and eccentricity and ventricular shape parameters were evaluated. P < 0.05 was adopted as statistical significance. Results At baseline, most patients were classified as NYHA 3 (n = 12). After CRT, 11 out of 18 patients were reclassified to a lower degree of functional limitation. In addition, patients' quality of life was improved post-CRT. Significant reductions were observed in QRS duration, PR interval, end-diastolic shape index, end-systolic shape index, stroke volume, and myocardial mass post-CRT. The CRT LV lead was positioned concordant, adjacent, and discordant in 11 (61.1%), 5 (27.8%), and 2 (11.1%) patients, respectively. End-systolic and end-diastolic eccentricity demonstrated reverse remodeling post-CRT. Conclusions LV lead implantation in CRT guided by gated SPECT scintigraphy is feasible. The placement of the electrode concordant or adjacent to the last segment to contract was a determinant of reverse remodeling.

[Analysis of Microbial Interaction Law of Mud Membrane in IFAS Process for Treating Low Carbon Source Sewage in South China].

To assess the problem of sewage treatment under the condition of low carbon sources, we carried out a study of activated sludge and a biofilm symbiosis system (IFAS). The occurrence characteristics and interaction law of microorganisms in two phases of sludge membrane under low carbon source conditions were discussed, and their niche and influence on treatment efficiency were clarified. Through a pilot-scale experiment in actual water plants, the biofilm characteristics, sludge membrane activity, and succession law of flora were analyzed, and the microbial structure and interaction in sludge membrane in two phases under the control of different activated sludge ages were compared. The results showed that the sludge concentration in the reactor increased with the increase in SRT under variable SRT. Because the microbial concentration in SRT-H was much higher than that in SRT-L, the competition between mud films in SRT-H was more intense than that in SRT-L, and the pollutant removal efficiency in SRT-H was lower than that in SRT-L. Under the condition of low-carbon feed water, the sludge activity in the IFAS process decreased with the increase in SRT. Under the condition of low SRT(5 d), the nitrification, denitrification, phosphorus accumulation, and phosphorus absorption rate of activated sludge increased by 122%, 88%, 34%, and 44%, respectively, compared with that of high SRT (25 d). However, SRT had little effect on biofilm activity, and there was little difference in nitrification activity and denitrification activity between the two SRTs. Microbial sequencing analysis showed that the functional bacteria of the IFAS process were enriched and transferred with the change in SRT between the two phases of mud membrane. In SRT-L, the functional bacteria that were enriched and transferred between the two phases of mud film owing to the "seeding" effect were mainly unclassified_g__Enterobacteriaceae, whereas in SRT-H, Acinetobacter was mainly used. At the same time, by analyzing the distribution of dominant functional bacteria, it was found that there was some competition between denitrifying bacteria and phosphorus-accumulating bacteria in activated sludge. Under the condition of a lack of organic substrate in the influent, the relative abundance of denitrifying bacteria was obviously higher than that of phosphorus-accumulating bacteria, which indicated that denitrifying bacteria could better adapt to low-carbon source conditions. Thus, they could occupy a dominant competition position, which was mainly reflected in the increase in the relative abundance of aerobic denitrifying bacteria. In addition, the SRT change in the mud phase reacted in the membrane phase, making the residence time of biofilm change correspondingly, thus changing the flora structure, screening out different dominant bacteria genera, and further increasing the difference.

Circular RNA 0001666 inhibits colorectal cancer cell proliferation, invasion and stemness by inactivating the Wnt/ß-catenin signaling pathway and targeting microRNA-1229.

A previous bioinformatics study suggested that circular RNA 0001666 (circ_0001666) and its target microRNA (miR)-1229 were associated with colorectal cancer (CRC) pathogenesis. However, the role of this interaction in the regulation of CRC cell malignancy remains unclear. Thus, the aim of the present study was to examine the interaction between circ_0001666 and miR-1229, and its effects on CRC cell malignancy. circ_0001666 overexpression or knockdown plasmids were transfected into the HT-29 and HCT-116 cell lines. In addition, in rescue experiments, circ_000166 or miR-1229 overexpression plasmids were transfected into the HT-29 cell line, either alone or in combination. Following transfection, cell proliferation, apoptosis, invasion and the number of CD133+ cells were analyzed. The protein expression level of proteins in the Wnt/ß-catenin pathway was also examined. In both HT-29 and HCT-116 cell lines, circ_0001666 overexpression increased apoptosis, whilst inhibiting cell proliferation and invasion, and reducing the frequency of CD133+ cells. By contrast, circ_0001666 knockdown reduced apoptosis, but increased cell proliferation and the number of CD133+ cells. However, cell invasion remained unaffected. In addition, circ_0001666 expression levels negatively regulated those of miR-1229, whereas miR-1229 expression did not affect circ_0001666, in both the HT-29 and HCT-116 cell lines. Furthermore, a luciferase reporter assay confirmed that miR-1229 directly bound to circ_0001666. In the HT-29 cell line, miR-1229 overexpression activated the Wnt/ß-catenin pathway, and promoted cell proliferation, invasion and stemness, while suppressing cell apoptosis. In addition, miR-1229 overexpression reversed the effects of circ_0001666 overexpression. In conclusion, circ_0001666 suppresses CRC cell proliferation, invasion and stemness by inhibiting the Wnt/ß-catenin signaling pathway by targeting miR-1229, and may represent a potential target for CRC treatment.

Development of an approach to extracting coronary arteries and detecting stenosis in invasive coronary angiograms.

Purpose: In stable coronary artery disease (CAD), reduction in mortality and/or myocardial infarction with revascularization over medical therapy has not been reliably achieved. Coronary arteries are usually extracted to perform stenosis detection. As such, developing accurate segmentation of vascular structures and quantification of coronary arterial stenosis in invasive coronary angiograms (ICA) is necessary. Approach: A multi-input and multiscale (MIMS) U-Net with a two-stage recurrent training strategy was proposed for the automatic vessel segmentation. The proposed model generated a refined prediction map with the following two training stages: (i) stage I coarsely segmented the major coronary arteries from preprocessed single-channel ICAs and generated the probability map of arteries; and (ii) during the stage II, a three-channel image consisting of the original preprocessed image, a generated probability map, and an edge-enhanced image generated from the preprocessed image was fed to the proposed MIMS U-Net to produce the final segmentation result. After segmentation, an arterial stenosis detection algorithm was developed to extract vascular centerlines and calculate arterial diameters to evaluate stenotic level. Results: Experimental results demonstrated that the proposed method achieved an average Dice similarity coefficient of 0.8329, an average sensitivity of 0.8281, and an average specificity of 0.9979 in our dataset with 294 ICAs obtained from 73 patients. Moreover, our stenosis detection algorithm achieved a true positive rate of 0.6668 and a positive predictive value of 0.7043. Conclusions: Our proposed approach has great promise for clinical use and could help physicians improve diagnosis and therapeutic decisions for CAD.

Application analysis of omental flap isolation and modified pancreaticojejunostomy in pancreaticoduodenectomy (175 cases).

BACKGROUND: To explore the application value of free omental wrapping and modified pancreaticojejunostomy in pancreaticoduodenectomy (PD). METHODS: The clinical data of 175 patients who underwent pancreaticoduodenectomy from January 2015 to December 2020 were retrospectively analysed. In total, 86 cases were divided into Group A (omental wrapping and modified pancreaticojejunostomy) and 89 cases were divided into Group B (control group). The incidences of postoperative pancreatic fistula and other complications were compared between the two groups, and univariate and multivariate logistic regression analyses were used to determine the potential risk factors for postoperative pancreatic fistula. Risk factors associated with postoperative overall survival were identified using Cox regression. RESULTS: The incidences of grade B/C pancreatic fistula, bile leakage, delayed bleeding, and reoperation in Group A were lower than those in Group B, and the differences were statistically significant (P < 0.05). Group A had an earlier drainage tube extubation time, earlier return to normal diet time and shorter postoperative hospital stay than the control group (P < 0.05). The levels of C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) inflammatory factors 1, 3 and 7 days after surgery also showed significant. Univariate and multivariate logistic regression analyses showed that a body mass index (BMI) ≥ 24, pancreatic duct diameter less than 3 mm, no isolation of the greater omental flap and modified pancreaticojejunostomy were independent risk factors for pancreatic fistula (P < 0.05). Cox regression analysis showed that age ≥ 65 years old, body mass index ≥ 24, pancreatic duct diameter less than 3 mm, no isolation of the greater omental flap isolation and modified pancreaticojejunostomy, and malignant postoperative pathology were independent risk factors associated with postoperative overall survival (P < 0.05). CONCLUSIONS: Wrapping and isolating the modified pancreaticojejunostomy with free greater omentum can significantly reduce the incidence of postoperative pancreatic fistula and related complications, inhibit the development of inflammation, and favourably affect prognosis.