Calculation of left ventricular ejection fraction using an 8-layer residual U-Net with deep supervision based on cardiac CT angiography images versus echocardiography: a comparative study.

Background: Accurate segmentation of the left ventricle (LV) is an important step in assessing cardiac function. Cardiac CT angiography (CCTA) has become an important means of clinical diagnosis of cardiovascular diseases (CVDs) because of its advantages of non-invasive, short examination time and low cost. In order to obtain the segmentation of LV in CCTA scans, we propose a deep learning method based on 8-layer residual U-Net with deep supervision. In this study we compared the left ventricular ejection fraction (LVEF) calculated by deep learning (DL) method (AccuLV) from CCTA to LVEF by conventional two-dimensional echocardiography (EC). Methods: This was a retrospective cross-sectional study, and consecutive patients who had undergone CCTA and EC in our hospital from February 2021 to May 2021 were recruited. The current study included 180 patients who had undergone CCTA and EC. To obtain LVEF, we used an 8-layer residual U-Net with deep supervision to segment LV contours from CCTA images and compute LVEF (DL-LVEF). The EC and DL-LVEF measurements were compared. A 50% EC-LVEF cut-off value was used as a reference standard to assess the diagnostic performance of AccuLV in assessing LV function. Results: The overall mean EC-LVEF and DL-LVEF values were 64.0% (52.3%, 69.0%) and 73.0% (52.3%, 77.0%), respectively. Three patient groups were studied: (I) hypertensive patients, (II) postmenopausal women, and (III) diabetes. EC-LVEF and DL-LVEF were found to be positively correlated for all of the included patients (r=0.82, P<0.001), with the detailed results for the three groups as follows: hypertensive patients (r=0.77, P<0.001), postmenopausal women (r=0.92, P<0.001) and diabetes (r=0.88, P<0.001). The diagnostic accuracy, sensitivity, and specificity of the DL method in predicting EC-LVEF <50% for all patients were 93.9%, 92.3%, and 94.3%, and for hypertensive patients were 95.4%, 93.8%, and 95.8%, for postmenopausal women were 87.0%, 100%, and 84.2%, for diabetes were 97.4%, 100%, and 96.6%. Conclusions: In comparison to echocardiography, which is commonly used in clinical setting, AccuLV may be a promising, fully automated tool for rapid and accurate quantification of LV function and thus for making reliable clinical decisions.

Characterization of cuproptosis in gastric cancer and relationship with clinical and drug reactions.

Gastric cancer (GC) is the fifth most common cancer worldwide. Cuproptosis is associated with cell growth and death as well as tumorigenesis. Aiming to lucubrate the potential influence of CRGs in gastric cancer, we acquired datasets of gastric cancer patients from TCGA and GEO. The identification of molecular subtypes with CRGs expression was achieved through unsupervised learning-cluster analysis. To evaluate the application value of subtypes, the K-M survival analysis was conducted to evaluate the clinical prognostic characteristics. Subsequently, we performed Gene Set Variation Analysis (GSVA) and utilized ssGSEA to quantify the extent of immune infiltration. Further, the K-M survival analysis was used to identify the prognosis-related CRGs. Next, signature genes of diagnostic predictive value were screened using the least absolute shrinkage and selection operator (LASSO) algorithm from the expression matrix for TCGA, as well as the signature gene-related subtype was clustered by the "ConsensusClusterPlus" package. Finally, the immunological and drug sensitivity assessments of the signature gene-related subtypes were conducted. A total of 173 CRGs were identified, most of the CRGs undergo copy number variation in gastric cancer. Under different patient subtypes, immune cell levels differed significantly, and the subtype exhibiting high expression of the CRGs had a better prognosis. Furthermore, we selected 34 CRGs that were highly correlated with the prognosis of gastric cancer. By constructing a multivariate Cox proportional-hazards model and a hazard scoring system, we were able to categorize patients into high- and low-risk groups based on their hazard score. K-M analysis demonstrated a significant survival disadvantage in the high-risk group. Based on Lasso regression analysis, we screened 16 signature genes, a multivariate logistic regression model [cutoff: 0.149 (0.000, 0.974), AUC:0.987] and a prognosis network diagram was constructed and their prediction efficiency for gastric cancer prognostic diagnosis was well validated. According to the signature genes, the patients were separated to two signature subtypes. We found that patients with higher CRGs expression and better prognosis had lower levels of immune infiltration. Finally, according to the results of drug susceptibility analysis, docetaxel, 5-Fluorouracil, gemcitabin, and paclitaxel were found to be more sensitive to gastric cancer.

Raptor couples mTORC1 and ERK1/2 inhibition by cardamonin with oxidative stress induction in ovarian cancer cells.

Background: A balance on nutrient supply and redox homeostasis is required for cell survival, and increased antioxidant capacity of cancer cells may lead to chemotherapy failure. Objective: To investigate the mechanism of anti-proliferation of cardamonin by inducing oxidative stress in ovarian cancer cells. Methods: After 24 h of drug treatment, CCK8 kit and wound healing test were used to detect cell viability and migration ability, respectively, and the ROS levels were detected by flow cytometry. The differential protein expression after cardamonin administration was analyzed by proteomics, and the protein level was detected by Western blotting. Results: Cardamonin inhibited the cell growth, which was related to ROS accumulation. Proteomic analysis suggested that MAPK pathway might be involved in cardamonin-induced oxidative stress. Western blotting showed that cardamonin decreased Raptor expression and the activity of mTORC1 and ERK1/2. Same results were observed in Raptor KO cells. Notably, in Raptor KO cells, the effect of cardamonin was weakened. Conclusion: Raptor mediated the function of cardamonin on cellular redox homeostasis and cell proliferation through mTORC1 and ERK1/2 pathways.

HAMP as a Potential Diagnostic, PD-(L)1 Immunotherapy Sensitivity and Prognostic Biomarker in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) remains a global medical problem. Programmed cell death protein 1 (PD-1) is a powerful weapon against many cancers, but it is not sensitive to some patients with HCC. We obtained datasets from the Gene Expression Omnibus (GEO) database on HCC patients and PD-1 immunotherapy to select seven intersecting DEGs. Through Lasso regression, two intersecting genes were acquired as predictors of HCC and PD-1 treatment prognosis, including HAMP and FOS. Logistic regression was performed to build a prediction model. HAMP had a better ability to diagnose HCC and predict PD1 treatment sensitivity. Further, we adapted the support vector machine (SVM) technique using HAMP to predict triple-classified outcomes after PD1 treatment in HCC patients, which had an excellent classification ability. We also performed external validation using TCGA data, which showed that HAMP was elevated in the early stage of HCC. HAMP was positively correlated with the infiltration of 18 major immune cells and the expression of 2 important immune checkpoints, PDCD1 and CTLA4. We discovered a biomarker that can be used for the early diagnosis, prognosis and PD1 immunotherapy efficacy prediction of HCC for the first time and developed a diagnostic model, prognostic model and prediction model of PD1 treatment sensitivity and treatment outcome for HCC patients accordingly.

CO2-Promoted and Nickel-Catalyzed Direct Hydroallylation of Terminal Alkynes with Allylic Alcohols: Access to 1,4-Dienes.

CO2-promoted and Ni-catalyzed direct hydroallylation of terminal alkynes with allylic alcohols has been achieved. Various 1,4-dienes could be synthesized in good yield with excellent Markovnikov selectivity for alkyl- and aryl-substituted terminal alkynes under mild reaction conditions. A gram-scale reaction gives considerable yield. Preliminary mechanistic studies support the reaction pathway through sequential carboxylation/allylnickelation/lithium bicarbonate nickelation/transmetalation in the hydroallylation of alkynes with allylic alcohols in the presence of CO2.

Visible-Light-Driven Reductive Carboxylation of Benzyl Bromides with Carbon Dioxide Using Formate as Terminal Reductant.

Cheap and available formate can be seen formally as a carbon dioxide radical anion (CO2•-) combined with a hydrogen atom, where the CO2•- is not only a highly active radical but also a very powerful reductant. In this paper, we successfully realized a visible-light-driven carboxylation of benzyl bromides with carbon dioxide to prepare high-value arylacetic acids using potassium formate as a terminal reductant. This reaction is characterized by mild reaction conditions and a wide range of substrates. Moreover, under nitrogen atmosphere, the reaction can also achieve the carboxylation of benzyl bromides utilizing an excess of potassium formate. Mechanistic experiments indicate this carboxylation proceeded through CO2•-, which was generated from the oxidation of 1,4-diazabicyclo[2.2.2]octane with excited photosensitizer Ir(ppy)2(dtbbpy)PF6 in the presence of the potassium formate.

Clinical Characteristics and Treatment Overview in Hand-Foot-and-Mouth Disease Using Real-World Evidence Based on Hospital Information System.

Objectives: To describe the epidemiological characteristics and medication overview of HFMD in Guangzhou and analyze the factors of length of stay (LOS) based on TCM usage. Method: From January 1, 2014, to June 30, 2019, clinical data of HFMD (ICD-10 B08.401) as the initial diagnosis, based on HIS of five medical institutions for outpatient and inpatient cases, was collected. The inpatient cases of the five hospitals in Guangzhou were utilized for hospitalization analysis. Information extracted from the warehouse was standardized. Descriptive analysis was used for baseline characteristics, medication usage, and inpatient characteristics. Potential factors were analyzed by bivariate analysis. COX regression analysis and Kaplan-Meier analysis for calculating HRs and 95% CIs were adopted to determine the predictors of LOS. Stratified COX regression was applied to analyze the relationship between predictors and LOS and to calculate interaction. Results: A total of 14172 patients with HFMD were included. It showed that HFMD would occur in males, infants, and summer. Cause and symptoms are the two aspects of conventional Western medicine treatments, while TCM treatment of HFMD took clearing heat and detoxification as the basic principle. Inpatients with HFMD were divided into two groups by the use ratio of TCM. Age, season, and disease severity were possible correlated factors of LOS, extrapolating from their disparity in distribution. By stratified Cox regression, three factors following presented as possible contributions to shortening LOS, including TCM ≥ 0.1 (HR = 1.79, 95% CI (1.67-1.92), P < 0.01), winter (HR = 1.28, 95% CI (1.12-1.47)), P < 0.01), mild HFMD (HR = 1.93, 95% CI (1.69-2.22), P < 0.01). Additive interaction of TCM use and disease severity was significant (RERI = 1.014 (0.493-1.534), P < 0.01). Conclusion: Young children and high temperature were the risk factors of HFMD infection, which suggests that increasing surveillance for susceptible particular-age individuals and season is indispensable. Favorable factors to decrease LOS included a higher proportion of TCM use, mild HFMD, and onset in winter. The proportion of TCM use had additive interaction with disease severity, indicating that TCM may have antiviral and other biological effects on HFMD. Increasing the proportion of TCM use was probably beneficial to shortening LOS.

Cardamonin suppresses pro-tumor function of macrophages by decreasing M2 polarization on ovarian cancer cells via mTOR inhibition.

Ovarian cancer is the most fatal tumor characterized by an abundance of tumor-associated macrophage (TAM) infiltrations in women. Functional TAMs, which mainly present M2-like phenotypes and perform key functions on tumor progress, have been considered an attractive target for ovarian cancer therapy. Cardamonin showed an excellent antitumor activity in multiple tumor cells. This study aimed to investigate the role of cardamonin on TAMs. With the conditioned medium of ovarian cancer cells, macrophages were induced to TAMs and, accordingly, promoted the proliferation, migration, and invasion of ovarian cancer cells. Cardamonin suppressed alternatively activated (M2) polarization of TAMs and downregulated TAM-secreted tumorigenic factors, thereby hindering the pro-tumor function of TAMs on ovarian cancer cells. Moreover, cardamonin inhibited tumor growth in xenograft nude mice and lowered the expression of CD163 and CD206. Mechanistically, cardamonin inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3), resulting in the suppression of M2 polarization. Furthermore, STAT3 is tightly related with mTOR activity. Altogether, these findings implied that cardamonin suppresses the pro-tumor function of TAMs by decreasing M2 polarization via mTOR inhibition, and cardamonin may be a potential therapeutic agent for ovarian cancer.

GPC2 Is a Potential Diagnostic, Immunological, and Prognostic Biomarker in Pan-Cancer.

Background: Glypican 2 (GPC2), a member of glypican (GPC) family genes, produces proteoglycan with a glycosylphosphatidylinositol anchor. It has shown its ascending significance in multiple cancers such as neuroblastoma, malignant brain tumor, and small-cell lung cancer. However, no systematic pan-cancer analysis has been conducted to explore its function in diagnosis, prognosis, and immunological prediction. Methods: By comprehensive use of datasets from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), Genotype-Tissue Expression Project (GTEx), cBioPortal, Human Protein Atlas (HPA), UALCAN, StarBase, and Comparative Toxicogenomics Database (CTD), we adopted bioinformatics methods to excavate the potential carcinogenesis of GPC2, including dissecting the correlation between GPC2 and prognosis, gene mutation, immune cell infiltration, and DNA methylation of different tumors, and constructed the competing endogenous RNA (ceRNA) networks of GPC2 as well as explored the interaction of GPC2 with chemicals and genes. Results: The results indicated that GPC2 was highly expressed in most cancers, except in pancreatic adenocarcinoma, which presented at a quite low level. Furthermore, GPC2 showed the early diagnostic value in 16 kinds of tumors and was positively or negatively associated with the prognosis of different tumors. It also verified that GPC2 was a gene associated with most immune-infiltrating cells in pan-cancer, especially in thymoma. Moreover, the correlation with GPC2 expression varied depending on the type of immune-related genes. Additionally, GPC2 gene expression has a correlation with DNA methylation in 20 types of cancers. Conclusion: Through pan-cancer analysis, we discovered and verified that GPC2 might be useful in cancer detection for the first time. The expression level of GPC2 in a variety of tumors is significantly different from that of normal tissues. In addition, the performance of GPC2 in tumorigenesis and tumor immunity also confirms our conjecture. At the same time, it has high specificity and sensitivity in the detection of cancers. Therefore, GPC2 can be used as an auxiliary indicator for early tumor diagnosis and a prognostic marker for many types of tumors.

Establishment and application of population pharmacokinetics model of vancomycin in infants with meningitis.

BACKGROUND: To establish a population pharmacokinetics (PPK) model of vancomycin (VCM) for dose individualization in Chinese infants with meningitis. METHODS: We collected the data of 82 children with meningitis in hospital from July 2014 to June 2016. The initial vancomycin dosage regimen for children was 10 or 15 mg/kg for q12 h, q8 h or q6 h. Serum concentrations were determined by Viva-E Analyzer before and after the fifth administration. The PPK model was developed by nonlinear mixed-effect model software, assessed by the bootstrap method and then tested in 20 infant patients. RESULTS: The VCM clearance (CL) was increased by body weight (WT) and decreased by blood urea nitrogen (BUN). Pharmacokinetic parameters of VCM were not influenced by co-administered drugs. The trough concentrations of VCM were accurately predicted by the PPK model, with the prediction errors less than 32%. CONCLUSION: A new individual strategy for VCM regimens was proposed and validated by the PPK model.

Network pharmacology integrated with experimental validation reveals the regulatory mechanism of plastrum testudinis in treating senile osteoporosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Plastrum testudinis (PT) has been used in traditional Chinese medicine to treat bone diseases such as senile osteoporosis (SOP) for thousands of years. However, the underlying mechanisms remain largely unknown. AIM OF THE STUDY: This study aims to investigate the possible molecular mechanism of PT in the treatment of SOP using an integrated strategy of network pharmacology and experimental validation. MATERIALS AND METHODS: The compounds of PT and its targets were identified through the BATMAN-TCM database. The SOP-related targets were retrieved from the GeneCards database. Protein-protein interaction information was obtained by inputting the intersection targets into the STRING database. Cytoscape software was used to construct a protein-protein interaction network and a PT-compound-target-SOP network. Using Cytoscape and R software, we conducted GO function and KEGG pathway enrichment analyses. We also conducted in vivo and in vitro experiments to verify the network pharmacology findings. RESULTS: In total, 6 active compounds and 342 targets of PT were screened, of which 57 common targets were related to SOP. The GO biological process enrichment analysis identified 880 entries, mainly relating to the regulation of hormone response, the cell apoptotic process, the apoptotic signaling pathway, NF-kappaB transcription factor activity, fatty acid transportation, osteoclast differentiation, macrophage activation, and inflammatory response. The KEGG pathway enrichment analysis identified 52 entries, including 14 related signaling pathways, which mainly involved the TNF, MAPK, IL-17, AGE-RAGE, estrogen, relaxin, and other signaling pathways. Our in vivo experiments confirmed that PT alleviates SOP, while the in vitro experiments demonstrated that PT exerts a suppressive effect on osteoclast differentiation and bone resorption in a concentration-dependent manner. Furthermore, we observed that PT downregulates the expression of osteoclast-specific genes, including C-FOS, TNF, and BDNF, in the MAPK signaling pathway. CONCLUSION: Through network pharmacology and experimental validation, this study is the first to report that PT downregulates the expression of osteoclast-specific genes, including C-FOS, TNF, and BDNF, in the MAPK signaling pathway, thus exerting a suppressive effect on osteoclast differentiation and bone resorption, which may be the molecular mechanism for PT treatment of SOP.

Linggui Zhugan Decoction for peripheral vertigo: A protocol for systematic review and meta-analysis.

BACKGROUND: Vertigo is a sense of movement or rotation of the patient's own or an external object. At present, western medicine treatment such as vestibular suppressant medications commonly used in clinical practice are ineffective and have adverse reactions. In traditional Chinese medicine, Linggui Zhugan Decoction (LZD) was used by doctors to warm yang for resolving fluid retention, strengthen the spleen and clear away dampness, with significant effect. Recently, some clinical studies have also shown that LZD has reliable effect in treating peripheral vertigo, but there is no systematic evidence. Therefore, this study aims to objectively evaluate the efficacy and safety of LZD in the treatment of peripheral vertigo. METHODS: Eight electronic databases will be searched from inception to August 2020 by 2 independent researchers, in order to collect qualified randomized controlled trials (RCTs) on the LZD treatment for peripheral vertigo. The therapeutic effects according to Clinical efficacy will be adopted as the primary outcomes. RevMan V.5.3 software will be used for the data synthesis and the Cochrane's risk of bias assessment tool will be used to assess the risk of bias. RESULTS: This review will conduct a high-quality synthesis on present evidence of LZD for peripheral vertigo. CONCLUSION: The conclusion of the study will indicate whether LZD is an effective treatment for peripheral vertigo by providing updated evidence. PROSPERO REGISTRATION NUMBER: PROSPERO CRD 42021238817.

DAP1 negatively regulates autophagy induced by cardamonin in SKOV3 cells.

Autophagy is closely related to the formation and development of multiple human tumors including ovarian cancer. As a major regulator of this process, the role of mTOR (mammalian target of rapamycin) has been well proven. Cardamonin, a kind of flavonoid from plants, has effects on induction of autophagy and thus antiproliferation of cancer cells. However, the detailed mechanism remains unclear. DAP1 (death-associated protein 1) is a proline-rich protein, which is involved in the regulation of cellular growth and programmed cell death including autophagy and apoptosis. The aim of this study was to investigate whether DAP1 is involved in proliferation inhibition and autophagy induced by cardamonin in tumor cells. Using online bioinformatics tools, we found that DAP1 expression is closely related to the survival of patients with ovarian cancer. Our study showed that autophagy induced by cardamonin was associated with mTOR inhibition, and DAP1 was involved in this process. Silence of DAP1 decreased cell proliferation but enhanced the antiproliferative effect of cardamonin in SKOV3 cells. The level of autophagy was elevated by DAP1 silencing in SKOV3 cells. Notably, cardamonin showed higher autophagy flux in the DAP1 small interfering RNA group. Taken together, our results implied that DAP1 negatively regulates autophagy induced by cardamonin, and it may be a potential target for ovarian cancer therapy.

Speech Emotion Recognition Based on Selective Interpolation Synthetic Minority Over-Sampling Technique in Small Sample Environment.

Speech emotion recognition often encounters the problems of data imbalance and redundant features in different application scenarios. Researchers usually design different recognition models for different sample conditions. In this study, a speech emotion recognition model for a small sample environment is proposed. A data imbalance processing method based on selective interpolation synthetic minority over-sampling technique (SISMOTE) is proposed to reduce the impact of sample imbalance on emotion recognition results. In addition, feature selection method based on variance analysis and gradient boosting decision tree (GBDT) is introduced, which can exclude the redundant features that possess poor emotional representation. Results of experiments of speech emotion recognition on three databases (i.e., CASIA, Emo-DB, SAVEE) show that our method obtains average recognition accuracy of 90.28% (CASIA), 75.00% (SAVEE) and 85.82% (Emo-DB) for speaker-dependent speech emotion recognition which is superior to some state-of-the-arts works.