Automated Classification Model With OTSU and CNN Method for Premature Ventricular Contraction Detection

Premature ventricular contraction (PVC) is one of the most common arrhythmias which can cause palpitation, cardiac arrest, and other symptoms affecting the work and rest activities of a patient. However, patients hardly decipher their own feelings to determine the severity of the disease thus, requiring a professional medical diagnosis. This study proposes a novel method based on image processing and convolutional neural network (CNN) to extract electrocardiography (ECG) curves from scanned ECG images derived from clinical ECG reports, and segment and classify heartbeats in the absence of a digital ECG data. The ECG curve is extracted using a comprehensive algorithm that combines the OTSU algorithm with erosion and dilation. This algorithm can efficiently and accurately separate the ECG curve from the ECG background grid. The performance of the classification model was evaluated and optimized using hundreds of clinical ECG data collected from Fujian Provincial Hospital. Additionally, thousands of clinical ECG reports were scanned to digital images as the test set to confirm the accuracy of the algorithm for practical application. Results showed that the average sensitivity, specificity, positive predictive value, and accuracy of the proposed model on the MIT-BIH dataset were 95.47%, 97.72%, 98.75%, and 98.25%, respectively. The classification average sensitivity, specificity, positive predictive value, and accuracy based on clinical scanned ECG images can reach to 97.24%, 81.6%, 83.8%, and 89.33%, respectively, and the clinical feasibility is high. Overall, the proposed method can extract ECG curves from scanned ECG images efficiently and accurately. Furthermore, it performs well on heartbeat classification of normal (N) and ventricular premature heartbeat

The changes of CD4+CD25+/CD4+ proportion in spleen of tumor-bearing BALB/c mice

CD4+CD25+ regulatory T lymphocytes (T(R)) constitute 5–10% of peripheral CD4+ T cells in naive mice and humans, and play an important role in controlling immune responses. Accumulating evidences show that T(R )cells are involved in some physiological processes and pathologic conditions such as autoimmune diseases, transplantation tolerance and cancer, and might be a promising therapeutic target for these diseases. To evaluate the change of CD4+CD25+ T(R )cells in mouse tumor models, CD4+CD25+ subset in peripheral blood and spleen lymphocytes from normal or C26 colon-carcinoma-bearing BABL/c mice were analyzed by flow cytometry using double staining with CD4 and CD25 antibodies. The proportion of CD4+CD25+/CD4+ in spleen lymphocytes was found to be higher than that in peripheral blood lymphocytes in normal mice. No difference was observed in the proportion in peripheral blood lymphocytes between tumor bearing mice and normal mice, while there was a significant increase in the proportion in spleen lymphocytes in tumor bearing mice as compared with normal mice. Moreover, the proportion increased in accordance with the increase in the tumor sizes. The increase in the proportion was due to the decrease in CD4+ in lymphocytes, which is resulted from decreased CD4+CD25- subset in lymphocytes. Our observation suggests the CD4+CD25+/CD4+ proportion in spleen lymphocytes might be a sensitive index to evaluate the T(R )in tumor mouse models, and our results provide some information on strategies of antitumor immunotherapy targeting CD4+CD25+ regulatory T lymphocytes

Coordination Chemistry of U(Ⅵ) With Acetohydroxamic Acid

The deprotonation of acetohydroxamic acid(AHA) and its coordination chemistry with uranyl ion(\begin{document}${\mathrm{UO}}_2^{2+ }$\end{document}) in 1.0 mol/L NaClO4 has been investigated with potentiometric titration and Raman spectroscopy at 25 ℃. For the first time, the deprotonations of AHA in aqueous solutions are quantitatively investigated with potentiometric titration method. It is found that in aqueous solution AHA acts as a monobasic acid and the protonation constants calculated to be pKa1=9.24±0.11(errors are given by the HyperQuad software fitting calculations). The determined pKa1 is in good agreement with the previously reported one-step protonation. In a wide pH range from acidic to basic aqueous solutions, the two step-wise protonation of AHA has been found, at the same time, the complexation of U(Ⅵ) with AHA has been re-visited. For AHA at different degrees of deprotonation, various complexes of U(Ⅵ) with AHA at ratios of U(Ⅵ) and AHA from 1∶1 to 1∶3 are recognized by potentiometric titration method. Amongst, the 1∶1 set of complexes consists of UO2A+ and UO2(OH)A, the 1∶2 includes UO2A2 and UO2(OH)\begin{document}${\mathrm{A}}_2^{-}$\end{document}, and the 1∶3 is composed of three complexes UO2\begin{document}${\mathrm{A}}_3^{-}$\end{document}, UO2(OH)\begin{document}${\mathrm{A}}_3^{2-}$\end{document} and UO2(OH)2\begin{document}${\mathrm{A}}_3^{3-}$\end{document}. There are maybe more complex species formed during the titrations, especially in very basic solutions, but those cannot be well quantitatively characterized due to their very low solubilities. The stability constants of the mentioned seven species have been determined by HyperQuad software, with the values of UO2A+ and UO2A2 in good consistence with those reported previously. All other five new-detected complexes are detected in solutions of relatively higher pH values. In the potentiometric titrations at relatively low AHA concentration, both protons of AHA can be deprotonated to form higher proportioned UO2(OH)A in comparison with UO2A2, which is an equal species to UO2A+ in term of releasing/consuming H+ during the titration process. At greatly excessive concentrations of AHA, three complexes, UO2A+, UO2A2, and UO2\begin{document}${\mathrm{A}}_3^{-}$\end{document} are successively formed with only one proton deprotonated A− as the pH being increased; further, two species, UO2(OH)\begin{document}${\mathrm{A}}_3^{2-}$\end{document} and UO2(OH)2\begin{document}${\mathrm{A}}_3^{3-}$\end{document}, are formed with partial of the ligands in the form of completely deprotonated (OH)A2−. The Raman spectroscopic titrations show that the Raman shift of O=U=O moves to lower wavenumbers with the increase in the number of ligands, with 849 cm−1, 828 cm−1 and 807 cm−1 corresponding to the three sets of U(Ⅵ) to AHA ratios of 1∶1, 1∶2, and 1∶3, respectively. Moreover, the results demonstrate that the effect of deprotonation on the Raman shifts of uranyl ion is negligible, but the effect on the Raman intensity is significant. The almost same step-wise Raman shifts at about 21 cm−1 for the three sets of complexes, 1∶1, 1∶2 and 1∶3, indicates a similar coordination mode for all the AHA ligands with different degrees of deprotonation, which provides informative hints for the structures of the complexes

Evidence for Positive Selection on the Leptin Gene in Cetacea and Pinnipedia

The leptin gene has received intensive attention and scientific investigation for its importance in energy homeostasis and reproductive regulation in mammals. Furthermore, study of the leptin gene is of crucial importance for public health, particularly for its role in obesity, as well as for other numerous physiological roles that it plays in mammals. In the present work, we report the identification of novel leptin genes in 4 species of Cetacea, and a comparison with 55 publicly available leptin sequences from mammalian genome assemblies and previous studies. Our study provides evidence for positive selection in the suborder Odontoceti (toothed whales) of the Cetacea and the family Phocidae (earless seals) of the Pinnipedia. We also detected positive selection in several leptin gene residues in these two lineages. To test whether leptin and its receptor evolved in a coordinated manner, we analyzed 24 leptin receptor gene (LPR) sequences from available mammalian genome assemblies and other published data. Unlike the case of leptin, our analyses did not find evidence of positive selection for LPR across the Cetacea and Pinnipedia lineages. In line with this, positively selected sites identified in the leptin genes of these two lineages were located outside of leptin receptor binding sites, which at least partially explains why co-evolution of leptin and its receptor was not observed in the present study. Our study provides interesting insights into current understanding of the evolution of mammalian leptin genes in response to selective pressures from life in an aquatic environment, and leads to a hypothesis that new tissue specificity or novel physiologic functions of leptin genes may have arisen in both odontocetes and phocids. Additional data from other species encompassing varying life histories and functional tests of the adaptive role of the amino acid changes identified in this study will help determine the factors that promote the adaptive evolution of the leptin genes in marine mammals

Comparison analysis of PD-1/PD-L1 inhibitors plus lenvatinib or gemcitabine/cisplatin as first-line treatment for patients with advanced intrahepatic cholangiocarcinoma

BackgroundIntrahepatic cholangiocarcinoma (ICC) is a highly aggressive primary liver cancer, with increasing incidence worldwide. Effective first-line treatments for advanced ICC patients are currently limited. Therefore, our study aimed to assess the efficacy and safety of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors in combination with gemcitabine/cisplatin (GC) and lenvatinib as first-line treatment in advanced ICC patients.MethodsThis retrospective cohort study included 51 advanced ICC patients, among whom 25 patients were administered with PD-1/PD-L1 plus lenvatinib and 26 patients were administered with PD-1/PD-L1 plus GC. Baseline characteristics including demographic information, medical history, clinical characteristics, laboratory data, and imaging examination were collected. The primary endpoints were progression-free survival (PFS) and sixth- and ninth-month overall survival (OS) rate. Survival curve was plotted by the Kaplan–Meier method. A Cox proportion risk model was performed to investigate independent risk factors of PFS and OS. The secondary outcomes were objective response rate (ORR), disease control rate (DCR), and adverse events.ResultsThe median age of advanced ICC patients in our study was 58.0 (95% confidence interval [95% CI] = 48.0–72.4) years, with 33 male and 18 female patients. Patients in the PD-1/PD-L1 inhibitors plus lenvatinib group were more likely to be in ECOG grade above 1, develop ascites, and have an elevated level of ALT. The ORR was 16.0% in the PD-1/PD-L1 inhibitors plus lenvatinib group and 23.1% in the GC group (p = 0.777). The DCR was 52.0% in the lenvatinib group and 46.2% in the GC group (p = 0.676). The combination treatment of PD-1/PD-L1 inhibitors plus lenvatinib was associated with longer PFS than the GC group; however, it was not statistically significant (lenvatinib: 9.5 months, GC: 5.1 months, p = 0.454). The sixth-month and ninth-month OS rates were 82.0% and 76.9% in the lenvatinib group and 87.4% and 71.5% in the GC group. After adjusting for confounders, multivariate Cox regression analysis showed that ECOG grade above 1 was an independent risk factor for PFS (hazard ratio [HR] = 3.388, 95% CI = 1.312–8.746, p = 0.012) and OS (HR = 4.220, 95% CI = 1.131–15.742, p = 0.032).ConclusionPD-1/PD-L1 inhibitors in combination with lenvatinib or GC all demonstrated significant efficacy and safety as first-line treatment in patients with advanced ICC. As for patients who refuse or are intolerant to chemotherapy, PD-1/PD-L1 plus lenvatinib would be recommended

Angiotensin-converting enzyme gene 2350 G/A polymorphism and susceptibility to atrial fibrillation in Han Chinese patients with essential hypertension

OBJECTIVE: The angiotensin-converting enzyme gene is one of the most studied candidate genes related to atrial fibrillation. Among the polymorphisms of the angiotensin-converting enzyme gene, the 2350 G/A polymorphism (rs4343) is known to have the most significant effects on the plasma angiotensin-converting enzyme concentration. The aim of the present study was to investigate the association of the angiotensin-converting enzyme 2350 G/A polymorphism with atrial fibrillation in Han Chinese patients with essential hypertension. METHODS: A total of 169 hypertensive patients were eligible for this study. Patients with atrial fibrillation (n = 75) were allocated to the atrial fibrillation group, and 94 subjects without atrial fibrillation were allocated to the control group. The PCR-based restriction fragment length polymorphism technique was used to assess the genotype frequencies. RESULTS: The distributions of the angiotensin-converting enzyme 2350 G/A genotypes (GG, GA, and AA, respectively) were 40.43%, 41.49%, and 18.08% in the controls and 18.67%, 46.67%, and 34.66% in the atrial fibrillation subjects (p = 0.037). The frequency of the A allele in the atrial fibrillation group was significantly greater than in the control group (58.00% vs. 38.83%, p = 0.0007). Compared with the wild-type GG genotype, the GA and AA genotypes had an increased risk for atrial fibrillation. Additionally, atrial fibrillation patients with the AA genotype had greater left atrial dimensions than the patients with the GG or GA genotypes (

Evaluation of human enterovirus 71 and coxsackievirus A16 specific immunoglobulin M antibodies for diagnosis of hand-foot-and-mouth disease

<p>Abstract</p> <p>Background</p> <p>Hand-foot-and-mouth disease (HFMD) is caused mainly by the human enterovirus type 71 (HEV71) and the Coxsackievirus A group type 16 (CVA16). Large outbreaks of disease have occurred frequently in the Asia-Pacific region. Reliable methods are needed for diagnosis of HFMD in childen. IgM-capture ELISA, with its notable advantages of convenience and low cost, provides a potentially frontline assay. We aimed to evaluate the newly developed IgM-capture ELISAs for HEV71 and CVA16 in the diagnosis of HFMD, and to measure the kinetics of IgM over the course of HEV71 or CVA16 infections.</p> <p>Results</p> <p>We mapped, for the first time, the kinetics of IgM in HEV71 and CVA16 infection. HEV71- and CVA16-IgM were both detectable in some patients on day 1 of illness, and in 100% of patients by day 5 (HEV71) and day 8 (CVA16) respectively; both IgMs persisted for several weeks. The IgM detection rates were 90.2% (138 of 153 sera) and 68.0% (66 of 97 sera) for HEV71 and CVA16 infections, respectively, during the first 7 days of diseases. During the first 90 days after onset these values were 93.6% (233 of 249 sera) and 72.8% (91 of 125 sera) for HEV71 and CVA16 infections, respectively. Some cross-reactivity was observed between HEV71- and CVA16-IgM ELISAs. HEV71-IgM was positive in 38 of 122 (31.1%) CVA16 infections, 14 of 49 (28.6%) other enteroviral infections and 2 of 105 (1.9%) for other respiratory virus infected sera. Similarly, CVA16-IgM was apparently positive in 58 of 211 (27.5%) HEV71 infections, 16 of 48 (33.3%) other enterovirus infections and 3 of 105 (2.9%) other respiratory virus infected sera. Nevertheless, the ELISA yielded the higher OD₄₅₀value of main antibody than that of cross-reaction antibody, successfully identifying the enteroviral infection in 96.6% (HEV71) and 91.7% (CVA16) cases. When blood and rectal swabs were collected on the same day, the data showed that the agreement between IgM-capture ELISA and real-time RT-PCR in HEV71 was high (Kappa value = 0.729) while CVA16 somewhat lower (Kappa value = 0.300).</p> <p>Conclusions</p> <p>HEV71- and CVA16-IgM ELISAs can be deployed successfully as a convenient and cost-effective diagnostic tool for HFMD in clinical laboratories.</p

The paradoxical patterns of expression of indoleamine 2,3-dioxygenase in colon cancer

<p>Abstract</p> <p>Background</p> <p>One of the putative mechanisms of tumor immune escape is based on the hypothesis that carcinomas actively create an immunosuppressed state via the expression of indoleamine 2,3-dioxygenase (IDO), both in the cancer cells and in the immune cells among the tumor-draining lymph nodes (TDLN). In an attempt to verify this hypothesis, the patterns of expression of IDO in the cancer cells and the immune cells among colon cancers were examined.</p> <p>Methods</p> <p>Seventy-one cases of pathologically-confirmed colon cancer tissues matched with adjacent non-cancerous tissues, lymph node metastases, and TDLN without metastases were collected at the Sun Yat-sen Cancer Center between January 2000 and December 2000. The expression of IDO and Bin1, an IDO regulator, was determined with an immunohistochemical assay. The association between IDO or Bin1 expression and TNM stages and the 5-year survival rate in colon cancer patients was analyzed.</p> <p>Results</p> <p>IDO and Bin1 were detected in the cytoplasm of cancer cells and normal epithelium. In primary colon cancer, the strong expression of IDO existed in 9/71 cases (12.7%), while the strong expression of Bin1 existed in 33/71 cases (46.5%). However, similar staining of IDO and Bin1 existed in the adjacent non-cancerous tissues. Among the 41 cases with primary colon tumor and lymph node metastases, decreased expression of IDO was documented in the lymph node metastases. Furthermore, among the TDLN without metastases, a higher density of IDO⁺cells was documented in 21/60 cases (35%). Both univariate and multivariate analyses revealed that the density of IDO⁺cells in TDLN was an independent prognostic factor. The patients with a higher density of IDO⁺cells in TDLN had a lower 5-year survival rate (37.5%) than the cells with a lower density (73.1%).</p> <p>Conclusion</p> <p>This study demonstrated paradoxical patterns of expression of IDO in colon cancer. The high density IDO⁺cells existed in TDLN and IDO was down-regulated in lymph nodes with metastases, implying that IDO in tumor and immune cells functions differently.</p

SPECIFIC NEUROPROTECTIVE EFFECTS OF MANUAL STIMULATION OF REAL ACUPOINTS VERSUS NON-ACUPOINTS IN RATS AFTER MIDDLE CEREBRAL ARTERY OCCLUSION

The objective of this study was to investigate the effectiveness and specific effects of acupuncture on ischemic-induced damage in rats after permanent middle cerebral artery occlusion. Cerebral ischemia was induced by middle cerebral artery occlusion in male Wistar rats. The rats were divided into the following 4 groups: normal controls, ischemic, real acupuncture-treated (Shuigou, DU26), and non-acupoint-treated groups. On the third postoperative day, neurological deficit scores, cerebral blood flow, infarction volume, and neuronal cell death counts were measured. In the real acupuncture-treated group, the neurological deficit scores and cerebral blood flow were improved (p < 0.05) and the infarction volume and neuronal cell death counts were reduced (p < 0.01) compared to the ischemic and non-acupoint-treated groups. The present study demonstrated that real acupuncture was effective against focal ischemia-induced damage in rats after middle cerebral artery occlusion, and the effects were specifically related to the right needling location

Redox memristors with volatile threshold switching behavior for neuromorphic computing

The spiking neural network (SNN), closely inspired by the human brain, is one of the most powerful platforms to enable highly efficient, low cost, and robust neuromorphic computations in hardware using traditional or emerging electron devices within an integrated system. In the hardware implementation, the building of artificial spiking neurons is fundamental for constructing the whole system. However, with the slowing down of Moore’s Law, the traditional complementary metal-oxide-semiconductor (CMOS) technology is gradually fading and is unable to meet the growing needs of neuromorphic computing. Besides, the existing artificial neuron circuits are complex owing to the limited bio-plausibility of CMOS devices. Memristors with volatile threshold switching (TS) behaviors and rich dynamics are promising candidates to emulate the biological spiking neurons beyond the CMOS technology and build high-efficient neuromorphic systems. Herein, the state-of-the-art about the fundamental knowledge of SNNs is reviewed. Moreover, we review the implementation of TS memristor-based neurons and their systems, and point out the challenges that should be further considered from devices to circuits in the system demonstrations. We hope that this review could provide clues and be helpful for the future development of neuromorphic computing with memristors