Estimation of left ventricular parameters based on deep learning method.

Estimating material properties of personalized human left ventricular (LV) modelling is a central problem in biomechanical studies. In this work we use deep learning (DL) method to evaluating the passive myocardial mechanical properties inversely. In the first part of the paper, we establish a standardized geometric model of the LV. The geometric model parameters are optimized based on 27 different healthy volunteers. In the second part, we use statistical methods and Latin hypercube sampling (LHS) to obtain the geometric parameters data. The LV myocardium is described using a structure-based orthotropic Holzapfel-Ogden constitutive law. The LV diastolic pressure-volume (PV) curves are calculated by numerical simulation. Tn the third part, we establish the multiple neural networks to pblackict PV curve parameters. Then, instead of using constrained optimization problems to solve constitutive parameters, DL was used to establish the nonlinear mapping relationship of geometric parameters, PV curve parameters and constitutive parameters. The results show that the deep learning method can greatly improve the computational efficiency of numerical simulation and increase the possibility of its application in rapid feedback of clinical data.

Meta-analysis on the effect of combining Lianhua Qingwen with Western medicine to treat coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a worldwide life-threatening pandemic. Lianhua Qingwen is believed to possess the ability to treat or significantly improve the symptoms of COVID-19. These claims make it important to systematically evaluate the effects of using Lianhua Qingwen with Western medicine to treat COVID-19. OBJECTIVE: To evaluate the safety and efficacy of combination therapy, employing Lianhua Qingwen with Western medicine, to treat COVID-19, using a meta-analysis approach. SEARCH STRATEGY: China National Knowledge Infrastructure, Wanfang Database, VIP Database, PubMed, Embase, and Cochrane Library databases were searched for studies evaluating the effect of Lianhua Qingwen-Western medicine combination therapy in the treatment of COVID-19. INCLUSION CRITERIA: (1) Research object: hospitalized patients meeting the diagnostic criteria of COVID-19 were included. (2) Intervention measures: patients in the treatment group received Lianhua Qingwen treatment combined with Western medicine, while the control group received either Western medicine or Chinese medicine treatment. (3) Research type: randomized controlled trials and retrospective study were included. DATA EXTRACTION AND ANALYSIS: Two researchers extracted the first author, the proportion of males and females, age, body temperature, course of treatment, rate of disappearance of main symptoms, duration of fever, adverse reactions, and total effectiveness from the literature. Odds ratio (OR) and 95% confidence interval (CI) were used as the effect value for count data, and mean difference (MD) and 95% CI were used as the effect value for measurement data. RESULTS: Six articles met the inclusion criteria, including a total of 856 COVID-19 patients. The meta-analysis showed that Lianhua Qingwen combination therapy achieved higher rates of fever reduction (OR = 3.43, 95% CI [1.78, 6.59], P = 0.0002), cough reduction (OR = 3.39, 95% CI [1.85, 6.23], P < 0.0001), recovery from shortness of breath (OR = 10.62, 95% CI [3.71, 30.40], P < 0.0001) and recovery from fatigue (OR = 2.82, 95% CI [1.44, 5.53], P = 0.003), higher total effectiveness rate (OR = 2.51, 95% CI [1.73, 3.64], P < 0.00001), and shorter time to recovery from fever (MD = -1.00, 95% CI [-1.04, 0.96], P < 0.00001), and did not increase the adverse reaction rate (OR = 0.65, 95% CI [0.42, 1.01], P = 0.06), compared to the single medication control. CONCLUSION: The Lianhua Qingwen and Western medicine combination therapy is highly effective for COVID-19 patients and has good clinical safety. As only a small number of studies and patients were included in this review, more high-quality, multicenter, large-sample-size, randomized, double-blind, controlled trials are still needed for verification.

Analysis of Bacterial Biofilm Formation in Patients with Malignancy Undergoing Double J Stent Indwelling and Its Influencing Factors.

OBJECTIVE: To analyze the bacterial biofilm (BF) formation in patients with malignancy undergoing double J stent indwelling and its influencing factors. METHODS: A total of 167 patients with malignant tumors who received double J stent indwelling in the hospital from January 2018 to January 2021 were included in the study. The urine and double J stent samples were collected for bacterial identification and observed for BF formation on the surface of the urinary catheter under a scanning electron microscope (SEM). Univariate and multivariate logistic regression analyses were used to analyze the influencing factors of BF. RESULTS: The BF formation rate was 34.73% (58/167). The BF formation rate of positive specimens cultured in urine and double J stent was significantly higher than that of negative ones (P<0.05). Staphylococcus was the main BF bacteria in double J stent and urine culture specimens, followed by Enterococcus, Pseudomonas, Enterobacter, and Acinetobacter. Compared with the non-BF group, the number of viable bacteria in the double J stent and urine and the catheterization time in the BF group rose markedly (P<0.05). Advanced age, chemotherapy, anemia, indwelling time ≥90d, and urinary tract infection were risk factors for BF formation in patients with malignancy undergoing double J stent indwelling (P<0.05). CONCLUSION: There is a high rate of BF formation in patients with malignancy undergoing double J stent indwelling, with Staphylococcus as the dominant species. Treatment requires enhanced urinary catheter management and nutritional status to inhibit BF formation and lower the rate of urinary catheter-related infections.

Azathioprine pretreatment ameliorates myocardial ischaemia reperfusion injury in diabetic rats by reducing oxidative stress, apoptosis, and inflammation.

This study was presented to observe the therapeutic effects of azathioprine (AZA) pretreatment on myocardial ischaemia reperfusion (I/R) damage in diabetic rats. All rats were randomly separated into control + sham operation; control +I/R; diabetes mellitus (DM) +I/R and DM +I/R + AZA groups. Diabetic rat models were established by intraperitoneally injecting 60 mg/kg streptozotocin (STZ). Diabetic rats were given 3 mg/kg AZA daily by gavage for 5 days. Then, myocardial I/R rat models were constructed. Myocardial infarction size and myocardial damage were respectively detected by TTC and H&E staining. Cardiac injury markers (CK-MB and MPO) and oxidative stress factors (SOD and MDA) were measured via ELISA. The protein expression of apoptotic markers (Caspase8, Caspase3, BAX and Bcl2), inflammatory factors (TLR4 and TNF-α) and AKT1/GSK3ß in myocardial tissues was measured by western blot, immunohistochemistry or immunofluorescence. Data showed that AZA pretreatment could lessen myocardial infarction size and myocardial damage, and could down-regulate serum CK-MB, MPO, SOD and MDA levels in diabetic rats under I/R. Furthermore, AZA pretreatment decreased Caspase8, Caspase3, BAX, TLR4 and TNF-α expression, and increased Bcl2 expression in myocardial tissues of diabetic rats following I/R. Also, AZA pretreatment lowered AKT1, p-AKT1, GSK3ß and p-GSK3ß expression in diabetic heart after I/R. This study found that AZA may reduce myocardial injury in diabetic rats following I/R via reducing oxidative stress, cardiomyocyte apoptosis, and inflammatory response, which could be related to AKT1/GSK3ß pathway inactivation.

Effect of indwelling time of double J tube on infected ureteral calculi and the distribution of pathogenic characteristics in diabetics.

OBJECTIVE: To investigate the effect of double J tube indwelling time on infected ureteral calculi (UC) and distribution of pathogenic characteristics in diabetics. METHODS: 132 diabetics with infected UC admitted to our hospital from April 2017 to April 2020 were selected. All patients were implanted with a double J tube, followed by percutaneous nephrolithotomy or ureteroscopic holmium laser lithotripsy. According to the indwelling time, they were divided into a research group (≤ 7 d, 60 cases) and a control group (> 7 d, 72 cases). We compared the baseline data, and surgical data of the two groups, and analyzed pathogenic bacteria. RESULTS: None of the differences in the operation time, hospital stay, and stone diameter were statistically significant (P > 0.05). Before placement of the double J tube, no striking differences in urinary white blood cells and blood white blood cells were observed between the two groups (P > 0.05). 7 days after the placement of the double J tube, a significant decrease of the urinary white blood cells and blood white blood cells was recorded (P < 0.05), with no significant differences between the two groups (P > 0.05). Before and after placement of double J tube, no striking differences in body temperature > 38.5°C or positive blood culture were observed between the two groups (P > 0.05). Surgical methods, stone removal rate one month after the operation, or incidence of postoperative complications were not significantly different (P > 0.05). 49 pathogenic strains were detected, among which Gram-negative bacteria accounted for 63.27%. The main pathogens were Escherichia coli and Pseudomonas aeruginosa. CONCLUSION: The indwelling time of the double J tube has no significant effect on the effectiveness and safety in diabetic patients with infected UC. It is necessary to reduce the indwelling time and implement targeted stone surgery.

Meta-analysis of mesh-plug repair and Lichtenstein repair in the treatment of primary inguinal hernia.

The present study systematically evaluated the clinical effects of mesh-plug and Lichtenstein herniorrhaphy in the treatment of primary inguinal hernia. PubMed, Embase, and the Cochrane Library (cut-off: May 25, 2020) databases were searched to select randomized controlled trials (RCTs) on mesh-plug and Lichtenstein herniorrhaphy for the treatment of primary inguinal hernia. Articles that met the inclusion criteria were screened and evaluated for quality. RevMan 5.3 software was used to perform a meta-analysis of operation time, discomfort in the inguinal region, haematoma, seroma, infection, time to return to normal activities, incidence of postoperative chronic pain, and recurrence rate. Eleven RCTs with 1457 patients in the mesh-plug group and 1472 in the Lichtenstein group were included. Meta-analysis showed that the mesh-plug herniorrhaphy group had a shorter operation time than the Lichtenstein herniorrhaphy group [P < 0.0001] but a longer time to return to normal activities after surgery [MD = 1.48, 95% CI (0.58, 2.38), P = 0.001]. There were no significant differences in postoperative discomfort in the inguinal region [P = 0.90], seroma [P = 0.10], haematoma [P = 0.27], infection [P = 0.40], incidence of postoperative chronic pain [P = 0.90], or recurrence rate [P = 0.77] between groups. Mesh-plug herniorrhaphy requires a shorter operation time than Lichtenstein herniorrhaphy, and there is no significant difference in postoperative complications or recurrence rate between the two methods. Clinical trial registration: INPLASY202070088. Meta-analysis of mesh -plug repair and Lichtenstein repair in the treatment of primary inguinal hernia.

Surrogate models based on machine learning methods for parameter estimation of left ventricular myocardium.

A long-standing problem at the frontier of biomechanical studies is to develop fast methods capable of estimating material properties from clinical data. In this paper, we have studied three surrogate models based on machine learning (ML) methods for fast parameter estimation of left ventricular (LV) myocardium. We use three ML methods named K-nearest neighbour (KNN), XGBoost and multi-layer perceptron (MLP) to emulate the relationships between pressure and volume strains during the diastolic filling. Firstly, to train the surrogate models, a forward finite-element simulator of LV diastolic filling is used. Then the training data are projected in a low-dimensional parametrized space. Next, three ML models are trained to learn the relationships of pressure-volume and pressure-strain. Finally, an inverse parameter estimation problem is formulated by using those trained surrogate models. Our results show that the three ML models can learn the relationships of pressure-volume and pressure-strain very well, and the parameter inference using the surrogate models can be carried out in minutes. Estimated parameters from both the XGBoost and MLP models have much less uncertainties compared with the KNN model. Our results further suggest that the XGBoost model is better for predicting the LV diastolic dynamics and estimating passive parameters than other two surrogate models. Further studies are warranted to investigate how XGBoost can be used for emulating cardiac pump function in a multi-physics and multi-scale framework.

PAX3 silencing inhibits prostate cancer progression through the suppression of the TGF-ß/Smad signaling axis.

Multiple studies have confirmed the pro-oncogenic effects of PAX3 in an array of cancers, but its role in prostate cancer (PCa) remains largely undefined. The aim of this study is to investigate the role of PAX3 in PCa. PAX3 expression was compared between PCa tumor tissue and nontumor tissues and PCa cell lines and normal prostate epithelial cells (PNT2) by western blot analysis and immunohistochemistry staining. MTT and immunofluorescence assays were used to detect PCa cell proliferation. Flow cytometry was used to evaluate cell apoptosis in PCa. Transwell assays were used for the determination of cell migration and PCa cell invasion. PAX3 expression was higher in PCa tissues and human PCa cell lines. Moreover, PAX3 silencing inhibited the proliferation, metastasis, and epithelial-mesenchymal transition (EMT) of PCa cells, and increased the rates of apoptosis. PAX3 silencing inhibited transforming growth factor-ß (TGF-ß)/Smad signaling in PCa cells. The effects of si-PAX3 on the proliferation, apoptosis, metastasis, and EMT of PCa cells were alleviated by TGF-ß1 treatment. PAX3 silencing inhibits PCa progression through the inhibition of TGF-ß/Smad signaling. This reveals PAX3 as a novel biomarker and therapeutic target for future PCa treatments.

O-linked N-acetylgalactosamine modification is present on the tumor suppressor p53.

BACKGROUND: Mucin-type O-glycosylation (referred to as O-GalNAc glycosylation) is the most abundant O-glycosylation on membrane and secretory proteins. Recently several evidences suggest that nuclear or cytoplasmic proteins might also have O-GalNAc glycosylation. However, what nucleocytoplasmic proteins are O-GalNAc glycosylated and what the biological function of this modification in cells are still poorly understood. Previously, we reported the tumor suppressor p53 could be O-GalNAc glycosylated in vitro. To investigate the existence and function of O-GalNAc glycosylation on nucleocytoplasmic proteins in cell, p53 as a representative nucleocytoplasmic protein was studied. METHODS: Using lectin blotting with GalNAc specific lectins, enzymatic treatments with O-GlcNAcase, core 1 ß1, 3-galactosyltransferase and O-glycosidase, and metabolic labeling with un-O-acetylated GalNAz in UDP-Gal/UDP-GalNAc 4-epimerase (GALE) knockout cells, we validated the O-GalNAc glycosylation on p53. Using mass spectrometry analysis and site-directed mutagenesis, we identified the glycosylated sites and studied the functions of O-GalNAc glycosylation on p53. RESULTS: The p53 was O-GalNAc glycosylated in cells. Ser121 residue was one of the glycosylated sites on p53. The O-GalNAc glycosylation at Ser121 was associated with the stability and activity of p53. CONCLUSIONS: These results revealed that the O-GalNAc glycosylation was a novel modification on p53. GENERAL SIGNIFICANCE: Our study provided a pilot evidence that the O-GalNAc glycosylation existed on nucleocytoplasmic protein.

Systematic identification of the protein substrates of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase-T1/T2/T3 using a human proteome microarray.

O-GalNAc glycosylation is the initial step of the mucin-type O-glycosylation. In humans, it is catalyzed by a family of 20 homologous UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts). So far, there is very limited information on their protein substrate specificities. In this study, we developed an on-chip ppGalNAc-Ts assay that could rapidly and systematically identify the protein substrates of each ppGalNAc-T. In detail, we utilized a human proteome microarray as the protein substrates and UDP-GalNAz as the nucleotide sugar donor for click chemistry detection. From a total of 16 368 human proteins, we identified 570 potential substrates of ppGalNAc-T1, T2, and T3. Among them, 128 substrates were overlapped, while the rest were isoform specific. Further cluster analysis of these substrates showed that the substrates of ppGalNAc-T1 had a closer phylogenetic relationship with that of ppGalNAc-T3 compared with ppGalNAc-T2, which was consistent with the topology of the phylogenetic tree of these ppGalNAc-Ts. Taken together, our microarray-based enzymatic assay comprehensively reveals the substrate profile of the ppGalNAc-T1, T2, and T3, which not only provides a plausible explanation for their partial functional redundancy as reported, but clearly implies some specialized roles of each enzyme in different biological processes.

Disulfide- and terminal alkyne-functionalized magnetic silica particles for enrichment of azido glycopeptides.

Disulfide- and terminal alkyne-modified magnetic silica particles (DA-MSPs) were synthesized and used to covalently capture and reductively release azido glycopeptides via click chemistry and dithiothreitol treatment. Using DA-MSPs, an efficient and specific enrichment method for separating azido glycopeptides has been developed.

Characterization of ppGalNAc-T18, a member of the vertebrate-specific Y subfamily of UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferases.

The first step of mucin-type O-glycosylation is catalyzed by members of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (ppGalNAc-T; EC 2.4.1.41) family. Each member of this family has unique substrate specificity and expression profiles. In this report, we describe a new subfamily of ppGalNAc-Ts, designated the Y subfamily. The Y subfamily consists of four members, ppGalNAc-T8, -T9, -T17 and -T18, in which the conserved YDX(5)WGGENXE sequence in the Gal/GalNAc-T motif of ppGalNAc-Ts is mutated to LDX(5)YGGENXE. Phylogenetic analysis revealed that the Y subfamily members only exist in vertebrates. All four Y subfamily members lack in vitro GalNAc-transferase activity toward classical substrates possibly because of the UDP-GalNAc-binding pocket mutants. However, ppGalNAc-T18, the newly identified defining member, was localized in the endoplasmic reticulum rather than the Golgi apparatus in lung carcinoma cells. The knockdown of ppGalNAc-T18 altered cell morphology, proliferation potential and changed cell O-glycosylation. ppGalNAc-T18 can also modulate the in vitro GalNAc-transferase activity of ppGalNAc-T2 and -T10, suggesting that it may be a chaperone-like protein. These findings suggest that the new Y subfamily of ppGalNAc-Ts plays an important role in protein glycosylation; characterizing their functions will provide new insight into the role of ppGalNAc-Ts.