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Antecedentes Pocos estudios han investigado el impacto del síndrome metabólico (SM) en la enfermedad por coronavirus 2019 (COVID-19). Describimos las características clínicas y el pronóstico de los pacientes con COVID-19 confirmados con SM durante la hospitalización y después del alta. Métodos Se incluyeron retrospectivamente 233 pacientes con COVID-19 de los hospitales de 8 ciudades de Jiangsu, China. Se describieron las características clínicas de los pacientes con COVID-19 y se analizaron los factores de riesgo de enfermedad grave mediante un análisis de regresión logística. Resultados Cuarenta y cinco (19,3%) de los 233 pacientes de COVID-19 tenían EM. La mediana de edad de los pacientes de COVID-19 con EM fue significativamente mayor que la de los pacientes sin EM (53,0 años frente a 46,0 años, P=0,004). No hubo diferencias significativas en cuanto a los síntomas clínicos, las imágenes de TC torácica anormales y los fármacos de tratamiento entre los dos grupos. Hubo más pacientes con EM que tuvieron enfermedades graves (33,3% frente a 6,4%, P

Background and Objectives: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) often lead to high mortality. Chronic obstructive pulmonary disease and asthma physiology score (CAPS) is a simple clinical severity score. The aim of this study was to explore whether CAPS could be an effective predictor for in-hospital and 1-year mortality in AECOPD patients. Methods. We used CAPS to grade all patients and record their clinical characteristics. The receiver operator characteristic (ROC) curve was used to determine the cut-off of CAPS that discriminated survivors and non-survivors. Univariate and multivariate logistic regression analyses and Cox regression analyses were used to identify the risk factors for in-hospital and 1-year mortality, respectively. Results. 240 patients were enrolled in our study; 18 patients died during hospitalization and 29 patients died during the 1-year follow-up. Compared with in-hospital survivors, those who died were older (80.83 ± 6.06 vs. 76.94 ± 8.30 years old, P = 0.019) and had a higher percentage of congestive heart failure (61.1% vs. 14.4%, P

The study aimed to investigate the incidence of and risk factors for liver damage in patients with human immunodeficiency virus type-1 (HIV-1) mono-infection receiving antiretroviral therapy (ART).We retrospectively analyzed the clinical data of patients who were diagnosed with HIV-1 infection and initiated ART from January to December 2017. Among them, 382 patients with HIV-1 mono-infection and normal baseline liver function were included in the analysis. The incidence of liver damage at each follow-up point, and possible risk factors for liver damage were evaluated via COX regression survival analyses.The overall incidence of liver damage (grade I-IV) was 27.23% (interquartile range [IQR]: 26.38%-28.72%). Grade I liver damage was most common and accounted for 22.13% of cases (IQR: 21.06%-24.04%), while grade II liver damage accounted for 3.40% of cases (IQR: 3.19%-4.26%). COX regression and survival analyses revealed that baseline body mass index (BMI), alanine aminotransferase (ALT) level, CD4Liver damage is common in patients with HIV-1 mono-infection undergoing ART. Patients with risk factors for liver damage should be well-informed before the initiation of ART, and liver function should be closely monitored during ART even in patients with normal liver function before ART.

Hepatic fibrosis is a damage repair response caused by multiple factors. A growing body of research suggests that long non-coding RNAs (lncRNAs) are involved in a wide range of biological processes, and thus regulate disease progression, including hepatic fibrosis. In this study, we investigated the mechanisms of the long non-coding RNA-non-coding RNA activated by DNA damage (NORAD) in modulating hepatic fibrosis development. Platelet-derived growth factor-BB (PDGF-BB) was used to activate LX-2 hepatic stellate cells (HSCs). The expression of NORAD and microRNA (miR)-495-3p was determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The effects of PDGF-BB on LX-2 cell viability, migration, invasion, and apoptosis were evaluated using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), Transwell, flow cytometry, and Western blot assays. The activation of HSCs was further verified by examining the expression of the typical markers, alpha smooth muscle actin (α-SMA) and collagen I (Col1α1), using qRT-PCR and Western blot assays. StarBase and dual-luciferase reporter assays were used to assess the binding relationship between miR-495-3p and NORAD. The NORAD levels remarkably increased, whereas the miR-495-3p levels decreased, in PDGF-BB-treated LX-2 cells. miR-495-3p was a putative downstream target of NORAD. NORAD silencing played an anti-fibrotic role by targeting miR-495-3p; this was accomplished by hindering PDGF-BB-treated LX-2 cell viability, migration, and invasion, decreasing the levels of α-SMA and Col1α1, and promoting apoptosis. miR-495-3p protected against hepatic fibrosis by inhibiting sphingosine 1-phosphate receptor 3 (S1PR3) expression. In summary, NORAD silencing inhibited hepatic fibrosis by suppressing HSC activation via the miR-495-3p/S1PR3 axis.

The nuclear factor kappa B (NF-κB) pathway and inhibitor of NF-κB kinase β (IKKβ) are involved in Alzheimer disease (AD) pathogenesis. This study explored the mechanisms underlying IKKβ-mediated Aβ aggregation and neuron regeneration in APP.PS1 mice. Adenoviral transduction particles were injected into the hippocampal CA1 region of the mice to knock down or inhibit target genes. Morris water maze was performed to evaluate the cognitive function of the mice. Aβ deposition was determined by histological examination. sh-IKKβ plasmids and microRNA (miR)-155-5p inhibitor were transfected into Aβ1-42-induced N2a cells. The expressions of AD-related proteins were detected by Western blot. The interaction between S-phase kinase-associated protein 2 (SKP2) and IKKβ was assessed by co-immunoprecipitation. IKKβ knockdown (KD) and miR-155-5p inhibition ameliorated cognitive impairment, improved neuron regeneration, and attenuated Aβ deposition in APP/PS1 mice. SKP2 KD aggravated cognitive impairment, inhibited neuron regeneration, and promoted Aβ deposition in the mice. SKP2 regulated the stability of IKKβ protein via ubiquitination. MiR-155-5p regulates Aβ deposition and the expression of Aβ generation-related proteins in N2a cells via targeting SKP2. These results indicate that the miR-155-5p/SKP2/IKKβ axis was critical for pathogenesis in this AD model and suggest the potential of miR-155-5p as a target for AD treatment.

Background Distant metastasis to vital organs is the major contributor to breast cancer mortality, and regional lymph node metastasis is an important facilitator of distant metastasis and recurrence in this cancer. The early diagnosis and precise treatment of lymph node metastasis are crucial for staging and prognosis in breast cancer. Herein, we report a visualized precision medicine nanoplatform of metastatic lymph nodes for ultrasonic/photoacoustic (US/PA) dual modal imaging-guided in situ targeted hyperthermia-combined chemotherapy. Results Carbon nanoparticles (CNs), approved by the China Food and Drug Administration, were loaded with docetaxel and rationally combined with anti-hypoxia-inducible factor 1α antibody-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles to achieve the combination of passive targeting at the lymph nodes and intracellular targeting at HIF 1α factor. The accumulation and retention of nanoparticles in metastatic lymph nodes via lymphatic delivery were enhanced. Docetaxel could be effectively offloaded by CNs that have active carbon nanoparticles, and the PLGA membrane prevented drug leakage. The nanoparticles exhibited excellent photothermal performance with a photothermal conversion efficiency of 28.9%, killing tumor cells in metastatic lymph nodes through hyperthermia. In vitro and in vivo systematic evaluations revealed that hyperpyrexia triggered the rupture of nanoparticles caused by the phase transition of perfluorohexane, resulting in docetaxel release for achieving in situ hyperthermia-combined chemotherapy. Conclusions The laser-triggered highly efficient in situ chemotherapy nanosystem achieves targeted synergistic chemo-hyperthermia treatment of metastatic lymph nodes, and lymphatic delivery represents a strategy to avoid additional injury caused by drugs entering the blood circulation. Graphical Abstract

MicroRNAs (miRNAs) are noncoding RNAs with 18–26 nucleotides; they pair with target mRNAs to regulate gene expression and produce significant changes in various physiological and pathological processes. In recent years, the interaction between miRNAs and their target genes has become one of the mainstream directions for drug development. As a large-scale biological database that mainly provides miRNA–target interactions (MTIs) verified by biological experiments, miRTarBase has undergone five revisions and enhancements. The database has accumulated >2 200 449 verified MTIs from 13 389 manually curated articles and CLIP-seq data. An optimized scoring system is adopted to enhance this update’s critical recognition of MTI-related articles and corresponding disease information. In addition, single-nucleotide polymorphisms and disease-related variants related to the binding efficiency of miRNA and target were characterized in miRNAs and gene 3′ untranslated regions. miRNA expression profiles across extracellular vesicles, blood and different tissues, including exosomal miRNAs and tissue-specific miRNAs, were integrated to explore miRNA functions and biomarkers. For the user interface, we have classified attributes, including RNA expression, specific interaction, protein expression and biological function, for various validation experiments related to the role of miRNA. We also used seed sequence information to evaluate the binding sites of miRNA. In summary, these enhancements render miRTarBase as one of the most research-amicable MTI databases that contain comprehensive and experimentally verified annotations. The newly updated version of miRTarBase is now available at https://miRTarBase.cuhk.edu.cn/.

There is still unmet demand for effective, safe, and patient-friendly anti-thrombotics to treat deep vein thrombosis (DVT) during pregnancy. Here we first engineer a bioactive amphiphile (TLH) by simultaneously conjugating Tempol and linoleic acid onto low molecular weight heparin (LMWH), which can assemble into multifunctional nanoparticles (TLH NP). In pregnant rats with DVT, TLH NP can target and dissolve thrombi, recanalize vessel occlusion, and eradicate the recurrence of thromboembolism, thereby reversing DVT-mediated intrauterine growth restriction and delayed development of fetuses. Mechanistically, therapeutic effects of TLH NP are realized by inhibiting platelet aggregation, facilitating thrombolysis, reducing local inflammation, attenuating oxidative stress, promoting endothelial repair, and increasing bioavailability. By decorating with a fibrin-binding peptide, targeting efficiency and therapeutic benefits of TLH NP are considerably improved. Importantly, LMWH nanotherapies show no toxicities to the mother and fetus at the dose 10-time higher than the examined therapeutic dosage.

BackgroundIn previous questionnaire surveys of miners, sleep disorders were found among underground workers. The influence of the special deep-underground environment and its potential mechanism are still unclear. Therefore, this study intends to utilize LC-MS metabolomics to study the potential differences between different environments and different sleep qualities.MethodsTwenty-seven miners working at 645–1,500 m deep wells were investigated in this study, and 12 local ground volunteers were recruited as the control group. The Pittsburgh Sleep Quality Index (PSQI) was used to examine and evaluate the sleep status of the subjects in the past month, and valuable basic information about the participants was collected. PSQI scores were obtained according to specific calculation rules, and the corresponding sleep grouping and subsequent analysis were carried out. Through liquid chromatography-mass spectrometry (LC-MS) non-targeted metabolomics analysis, differences in metabolism were found by bioinformatics analysis in different environments.ResultsBetween the deep-underground and ground (DUvsG) group, 316 differential metabolites were identified and 125 differential metabolites were identified in the good sleep quality vs. poor sleep quality (GSQvsPSQ) group. The metabolic pathways of Phenylalanine, tyrosine and tryptophan biosynthesis (p = 0.0102) and D-Glutamine and D-glutamate metabolism (p = 0.0241) were significantly enriched in DUvsG. For GSQvsPSQ group, Butanoate metabolism was statistically significant (p = 0.0276). L-Phenylalanine, L-Tyrosine and L-Glutamine were highly expressed in the deep-underground group. Acetoacetic acid was poorly expressed, and 2-hydroxyglutaric acid was highly expressed in good sleep quality.ConclusionsThe influence of the underground environment on the human body is more likely to induce specific amino acid metabolism processes, and regulate the sleep-wake state by promoting the production of excitatory neurotransmitters. The difference in sleep quality may be related to the enhancement of glycolytic metabolism, the increase in excitatory neurotransmitters and the activation of proinflammation. L-phenylalanine, L-tyrosine and L-glutamine, Acetoacetic acid and 2-hydroxyglutaric acid may be potential biomarkers correspondingly.

To detect the expression of multiple myeloma-associated antigen (MMSA)-8 and MMSA-1 in bone marrow mononuclear cells of patients with acute myeloid leukemia, and explore their roles in acute myeloid leukemia.A total of 83 patients with M2 acute myeloid leukemia in our hospital from January 2019 to January 2020 were selected as research group, during the same period, 15 patients diagnosed iron deficiency anemia were selected as control group. Real-time fluorescence quantitative PCR was used to detect the levels of MMSA-8 and MMSA-1 in bone marrow mononuclear cells. Patients in the research group were divided into remission and non remission according to the clinical curative effect, and were divided into good prognosis, medium prognosis, and poor prognosis according to the prognosis. The relationship between MMSA-8, MMSA-1 and clinical efficacy, prognosis was analyzed. In addition, the general data of patients in the research group were collected, including white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT), and percentage of bone marrow progenitor cells at admission. Pearson method was used to analyze the correlation between MMSA-8, MMSA-1 and clinical data, and MMSA-8 and MMSA-1.The analysis results about mRNA levels of MMSA-8 and MMSA-1 in bone marrow mononuclear cells of patients showed that patients in the research group were significantly higher than those in the control group (P0.05); In the research group, patients without remission were also significantly higher than those with remission, as well as those with medium and poor prognosis than with good prognosis, while only mRNA level of MMSA-1 in patients with poor prognosis was significantly higher than those with medium prognosis (P0.05). Pearson analysis showed that MMSA-8, MMSA-1 were positively correlated with WBC (r=0.468, r=0.516), and MMSA-8 was positively correlated with MMSA-1 (r=0.318).The levels of MMSA-8 and MMSA-1 in bone marrow mononuclear cells of patients with M2 acute myeloid leukemia are increased, which are closely related to the occurrence and development of the disease, and have certain value for the prognosis.M2型急性髓系白血病患者骨髓中MMSA-8、MMSA-1表达及临床意义.检测急性髓系白血病患者骨髓单个核细胞中多发性骨髓瘤相关抗原（MMSA）-8、MMSA-1表达情况，探讨二者在急性髓系白血病中的临床意义。.纳入2019年1月-2020年1月本院M2型急性髓系白血病患者83例为研究组，同期血液科诊断为单纯缺铁性贫血患者15例为对照组，实时荧光定量PCR检测骨髓单个核细胞中MMSA-8、 MMSA-1表达水平。将研究组患者根据疗效分为缓解、未缓解，根据预后状况分为预后良好、预后中等和预后不良，分析MMSA-8、MMSA-1与疗效、预后的关系。另收集研究组患者的一般资料，包括入院时血常规白细胞数、血红蛋白、血小板数和骨髓原始细胞百分比，Pearson法分析MMSA-8、MMSA-1与患者临床资料以及MMSA-8与MMSA-1的相关性。.对患者骨髓单个核细胞中MMSA-8、MMSA-1 mRNA水平分析结果显示，研究组患者明显高于对照组患者（P0.05）；研究组中未缓解患者明显高于缓解患者（P0.05），预后中等、预后不良患者均明显高于预后良好患者（P0.05），预后不良患者仅MMSA-1 mRNA水平明显高于预后中等患者（P0.05）。Pearson法分析结果显示，研究组患者MMSA-8、MMSA-1与白细胞数呈正相关（r=0.468，r=0.516），MMSA-8与MMSA-1呈正相关（r=0.318）。.M2型急性髓系白血病患者骨髓单个核细胞中MMSA-8、MMSA-1水平升高，二者均与疾病发生发展关系密切，且对预后有一定预测价值。.

Remote photoplethysmography (rPPG) is a non-contact technique for measuring cardiac signals from facial videos. High-quality rPPG pulse signals are urgently demanded in many fields, such as health monitoring and emotion recognition. However, most of the existing rPPG methods can only be used to get average heart rate (HR) values due to the limitation of inaccurate pulse signals. In this paper, a new framework based on generative adversarial network, called PulseGAN, is introduced to generate realistic rPPG pulse signals through denoising the chrominance signals. Considering that the cardiac signal is quasi-periodic and has apparent time-frequency characteristics, the error losses defined in time and spectrum domains are both employed with the adversarial loss to enforce the model generating accurate pulse waveforms as its reference. The proposed framework is tested on the public UBFC-RPPG database in both within-database and cross-database configurations. The results show that the PulseGAN framework can effectively improve the waveform quality, thereby enhancing the accuracy of HR, the heart rate variability (HRV) and the interbeat interval (IBI). The proposed method achieves the best performance compared to the denoising autoencoder (DAE) and CHROM, with the mean absolute error of AVNN (the average of all normal-to-normal intervals) improving 20.85% and 41.19%, and the mean absolute error of SDNN (the standard deviation of all NN intervals) improving 20.28% and 37.53%, respectively, in the cross-database test. This framework can be easily extended to other existing deep learning based rPPG methods, which is expected to expand the application scope of rPPG techniques., 10 pages, 11 figures

To identify the factors of family management affecting asthma control status in school-age children with asthma in China.The cross-sectional descriptive study was conducted among 139 children with asthma and their parents. The age range of the children was 7 to 14 years of age (MFactors significantly associated with asthma control were "Follow-Up Plan" (OR, 2.004; 95% CI, 1.009-3.981), "Attended a Lecture on asthma" (OR, 2.586; 95% CI, 1.103-6.066) and two dimensions of the FMSCA, "Children Identity" (OR = 1.133; 95% CI, 1.024-1.254) and "Family Focus" (OR = 1.114; 95% CI, 1.007-1.232).This study shows that asthma control status of school-age children in China is related to the parents' views of their child as having a "normal condition" and the parents' satisfaction with the balance between asthma related management and other aspects of family life.

Background/aim Estrogen receptor α (ERα) antagonist is the most common treatment for ERα-positive breast cancer. However, compensatory signaling contributes to resistance to ERα antagonists. Thus, to explore the potential agents for targeting compensatory signaling, we screened multiple target inhibitors for breast cancer treatment. Materials and methods We attempted to build a structure-based virtual screening model that can find potential compounds and assay the anticancer ability of these drugs by overall cell survival assay. The downstream compensatory phosphorylated signaling was measured by immunoblotting. Results Hamamelitannin and glucocheirolin were hits for ERα, phosphoinositide 3-kinase (PI3K), and KRAS proto-oncogene, GTPase (KRAS), which were active against estrogen and epidermal growth factor-triggered proliferation. Additionally, we select aminopterin as a hit for ERα, PI3K, KRAS, and SRC proto-oncogene, non-receptor tyrosine kinase (SRC) with inhibitory activities toward AKT serine/threonine kinase 1 (AKT) and mitogen-activated protein kinase kinase (MEK) signaling. Conclusion Our structure-based virtual screening model selected hamamelitannin, glucocheirolin, aminopterin, and pemetrexed as compounds that may act as potential inhibitors for improving endocrine therapies for breast cancer.

Bleeding is the most common adverse reaction to aspirin and can lead to drug discontinuation or even be life-threatening in the secondary prevention of stroke or transient ischemic attack. The aim of this study was to evaluate risk factors for bleeding adverse reaction of aspirin in ischemic stroke or transient ischemic attack.This retrospective analysis included patients treated with aspirin (100 mg) as a secondary prevention for ischemic stroke or transient ischemic attack. The bleeding events that occurred during the first year were collected, including gastrointestinal, skin, nasal cavity, gum, and urinary tract bleeding events. Then, univariate and multivariate logistic regression analyses were used to identify independent factors associated with bleeding events of aspirin.A total of 578 patients were enrolled in this study, and 58 patients developed bleeding during the first year of secondary prevention. Body weight and combination with selective serotonin reuptake inhibitors were found to be significant risk factors for overall bleeding (p = 0.025 and 0.012). Body weight below 60 kg was a risk factor for overall bleeding and gastrointestinal bleeding events.Patients weighing less than 60 kg were at increased risk of bleeding with 100 mg aspirin for secondary prevention of cerebral infarction transient ischemic attack.

To explore the effect of carvacrol on the biological behavior of leukemia cells and its regulation to circ-0008717/miR-217 molecular axis.Human acute lymphoblastic leukemia cells Molt-4 were cultured in vitro, and different concentrations of carvacrol were added to the cells. si-NC and si-circ-0008717 were transfected into Molt-4 cells (si-NC group, si-circ-0008717 group). pcDNA, pcDNA-circ-0008717, anti-miR-NC, anti-miR-217 were transfected into Molt-4 cells and then added to carvacrol-treated cells (carvacrol+pcDNA group, carvacrol+pcDNA-circ-0008717 group, carvacrol+anti-miR-NC group, carvacrol+anti-miR-217 group). MTT, plate clone formation experiment, and flow cytometry were used to detect the viability of the cell, colony formation number, and apoptosis rate of cells, respectively. The RT-qPCR method was used to detect the expression levels of circ-0008717 and miR-217. The dual luciferase reporter gene experiment was used to detect the targeting relationship between circ-0008717 and miR-217.After carvacrol treatment, the cell viability decreased significantly (r=-0.9405), expression level of circ-0008717 decreased (r=-0.9117), colonies formed number decreased (r=-0.9256), while the cell apoptosis rate increased (r= 0.8464), and the expression level of miR-217 increased (r=0.9468). Compared with the si-NC group, the expression level of miR-217 in si-circ-0008717 group increased (P＜0.001), the cell apoptosis rate increased (P＜0.001), while cell viability decreased (P＜0001), the number of colonies formed decreased (P＜0.001). Compared with the carvacrol+pcDNA group, the cell viability of the carvacrol+pcDNA-circ-0008717 group increased (P＜0.001), the number of colonies formed increased (P＜0.001), while the cell apoptosis rate decreased (P＜0.001). circ-0008717 could target miR-217. The cell viability of the carvacrol+anti-miR-217 group increased (P＜0.001), and the number of colonies formed increased (P＜0.001), while the cell apoptosis rate decreased (P＜0001) as compared with the carvacrol+anti-miR-NC group.Carvacrol can promote the expression of miR-217 by down-regulating the expression of circ-0008717, thereby reducing the proliferation and cloning ability of leukemia cells and promoting cell apoptosis.香芹酚对白血病细胞生物学行为的影响及其机制.探讨香芹酚对白血病细胞生物学行为的影响及其对circ-0008717/miR-217分子轴的调控作用.体外培养人急性淋巴细胞白血病细胞Molt-4，分别加入不同浓度的香芹酚处理细胞；si-NC、si-circ-0008717分别转染入Molt-4细胞（si-NC组、si-circ-0008717组），pcDNA、pcDNA-circ-0008717、anti-miR-NC、anti-miR-217分别转染入Molt-4细胞后加入香芹酚处理细胞（香芹酚+pcDNA组、香芹酚+pcDNA-circ-0008717组、香芹酚+anti-miR-NC组、香芹酚+anti-miR-217组）；MTT、平板克隆形成实验、流式细胞术分别检测细胞活力、集落形成数、细胞凋亡率；RT-qPCR法检测circ-0008717和miR-217的表达量；双荧光素酶报告基因实验检测circ-0008717与miR-217的靶向关系.经香芹酚处理后，细胞活力明显降低（r=-0.9405），circ-0008717的表达水平明显降低（r=-0.9117），集落形成数明显减少（r=-0.9256），细胞凋亡率明显升高（r=0.8464），miR-217的表达水平明显升高（r=0.9468）；与si-NC组比较，si-circ-0008717组miR-217的表达水平升高（P＜0.001），细胞活力降低（P＜0001），集落形成数明显减少（P＜0.001），细胞凋亡率升高（P＜0.001）；与香芹酚+pcDNA组比较，香芹酚+pcDNA-circ-0008717组细胞活力升高（P＜0.001），集落形成数明显增多（P＜0.001），细胞凋亡率明显降低（P＜0001）；circ-0008717可靶向调控miR-217的表达；与香芹酚+anti-miR-NC组比较，香芹酚+anti-miR-217组细胞活力明显升高（P＜0.001），集落形成数明显增多（P＜0.001），细胞凋亡率明显降低（P＜0.001）.香芹酚可通过下调circ-0008717的表达而促进miR-217的表达从而减弱白血病细胞增殖、克隆形成能力及促进细胞凋亡.

Sphingomyelin synthase 2 (SMS2) is a vital contributor to tissue injury and affects various pathological processes. However, whether SMS2 participates in the modulation of cardiac injury in myocardial infarction has not been determined. This study aimed to evaluate the potential role of SMS2 in the regulation of cardiomyocyte injury induced by hypoxia, an in vitro model for studying myocardial infarction. Our data revealed that SMS2 expression was significantly upregulated in cardiomyocytes in response to hypoxia. Loss-of-function experiments revealed that knockdown of SMS2 markedly restored the viability of cardiomyocytes impaired by hypoxia, and attenuated hypoxia-evoked apoptosis and reactive oxygen species (ROS) generation. In contrast, cardiomyocytes that highly expressed SMS2 were more sensitive to hypoxia-induced injury. Moreover, SMS2 deficiency enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling through inactivation of glycogen synthase kinase-3β. Notably, suppression of Nrf2 markedly abrogated SMS2 knockdown-mediated cardioprotective effects on hypoxia-exposed cardiomyocytes. Our results illustrate that downregulation of SMS2 exerts a cardioprotective function by protecting cardiomyocytes from hypoxia-induced apoptosis and oxidative stress through enhancement of Nrf2 activation. Our study indicates a potential role of SMS2 in the modulation of cardiac injury, which may contribute to the progression of myocardial infarction.

Semen analysis plays an important role in the diagnosis of male infertility. However, many studies have demonstrated that the current methods of semen analysis are inefficient for assessing male fertility.To test whether prior discontinuous density gradient centrifugation (DDCG) improves the performance of semen analysis in diagnosing male infertility.Infertile men and fertile men were recruited from the clinic. Pre- and post-DDGC values for the semen parameters of sperm concentration, total sperm number, percent total motility, percent progressive motility, percent normal sperm morphology, and sperm DNA fragmentation rate were compared.A total of 528 men (252 infertile men and 276 fertile men) were enrolled in the present study. After DDGC, sensitivity was significantly increased for sperm concentration, total sperm number, and sperm morphology (P .01); specificity was significantly increased for progressive motility and sperm morphology (P .01); and diagnostic accuracy was significantly improved for all of these parameters (area under the curve (AUC): P .01). Total motility and sperm DNA fragmentation rate exhibited no obvious change in sensitivity, specificity or accuracy after DDGC (all P .01). For the combination of all these semen parameters, diagnostic accuracy improved significantly after DDGC (AUC: P .01). In a multiple regression analysis, only sperm morphology and sperm DNA fragmentation rate had P values less than 0.05 before DDGC, whereas all parameters except total sperm number contributed to the equation after DDGC.DDGC is a mature, standardized procedure for clinical commonly used to optimize spermatozoa. The diagnostic accuracy of semen analysis was significantly improved after DDGC, which indicated that assessing "functional spermatozoa" might be a more suitable method for semen analysis than the WHO 2010 criteria.Assessing semen parameters after DDGC might improve their diagnostic accuracy for male infertility.

Sitafloxacin, a new fluoroquinolone, has strong antibacterial activity. We evaluated the effects of sitafloxacin granules in single‐dose and multidose cohorts and the effects of ABCB1, UGT1A1, and UGT1A9 genetic polymorphisms on the pharmacokinetics (PK) of sitafloxacin in healthy subjects. The single‐dose study included 3 fasted cohorts receiving 50, 100, and 200 mg of sitafloxacin granules and 1 cohort receiving 50 mg of sitafloxacin granules with a high‐fat meal. The multidose study included 1 cohort receiving 100 mg of sitafloxacin granules once daily for 5 days. PK parameters were calculated using noncompartmental parameters based on concentration‐time data. The genotypes for ABCB1, UGT1A1, and UGT1A9 single‐nucleotide polymorphisms were determined using Sanger sequencing. Subsequently, the association between sitafloxacin PK parameters and target single‐nucleotide polymorphisms was analyzed. Sitafloxacin granules were well tolerated up to 200 and 100 mg in the single‐dose and multidose studies, respectively. Sitafloxacin AUC and Cmax increased linearly within the detection range, and a steady state was reached within 3 days after the administration of multiple oral doses. Our findings showed that Cmax was lower in the ABCB1 (rs1045642) mutation group, whereas t1/2 was longer in the UGT1A1 (rs2741049) and UGT1A9 (rs3832043) mutation groups. In conclusion, sitafloxacin granules were safe at single doses and multiple doses up to 200 and 100 mg/day, respectively, with a linear plasma PK profile. However, ABCB1 (rs1045642), UGT1A1 (rs2741049), and UGT1A9 (rs3832043) genetic polymorphisms are likely to influence the Cmax or t1/2 and thereby merit further clinical evaluation.

DNA methylation has been implicated as an important mechanism for the development of uterine corpus endometrial carcinoma (UCEC), indicating that methylation-driven genes may be potential biomarkers for survival prediction. In this study, we aimed to identify a new prognostic methylation signature for UCEC based on differentially expressed genes (DEGs) and long noncoding RNAs (lncRNAs) (DELs). Sample-matched RNA-sequencing and methylation-array data were downloaded from The Cancer Genome Atlas database, by analysis of which a total of 269 DEGs and 4 DELs were identified to be methylation driven. Least absolute shrinkage and selection operator analysis screened that 14 methylation-driven genes were significantly associated with overall survival (OS) and thus were used as a signature to establish a prognostic risk model. Based on the median threshold, the patients were divided into the low-risk and the high-risk groups, which showed significantly different survival periods under the Kaplan-Meier curve. The area under receiver operating characteristic curve (AUC) was 0.934, 0.919, and 0.952 for the training, validation, and entire cohort, respectively. Stratification analysis showed that the established risk model may add prognostic values to conventional clinical factors (age, neoplasm histologic grade, and clinical stage). A nomogram was constructed based on the risk model and clinical parameters, with the AUC of 0.978 and c-index of 0.8079. Database for Annotation, Visualization, and Integrated Discovery (DAVID) function enrichment and Human Protein Atlas (HPA) protein expression validation showed 5 of these 14 genes may be especially important for UCEC (hypermethylated lowly expressed: CCBE1, FOXL2, PHLDB2, and DTNA; hypomethylated highly expressed: CCNE1). Comparison with breast cancer in the methylation level indicated ABCA12, CCNE1, and CLRN3 may be specific methylation-driven genes for UCEC. LncRNA HCG11 may function by coexpressing with DTNA. In conclusion, this 14-DNA methylation signature combined with clinical factors may a potentially effective biomarker in predicting OS for UCEC patients.

This study aims to explore lipidic mechanism towards low‐density lipoprotein receptor (LDLR)‐mediated platinum chemotherapy resistance. By using the lipid profiling technology, LDLR knockdown was found to increase lysosomal lipids and decrease membranous lipid levels in EOC cells. LDLR knockdown also down‐regulated ether‐linked phosphatidylethanolamine (PE‐O, lysosomes or peroxisomes) and up‐regulated lysophosphatidylcholine [LPC, lipid droplet (LD)]. This implies that the manner of using Lands cycle (conversion of lysophospholipids) for LDs might affect cisplatin sensitivity. The bioinformatics analyses illustrated that LDLR‐related lipid entry into LD, rather than an endogenous lipid resource (eg Kennedy pathway), controls the EOC prognosis of platinum chemotherapy patients. Moreover, LDLR knockdown increased the number of platinum‐DNA adducts and reduced the LD platinum amount. By using a manufactured LPC‐liposome‐cisplatin (LLC) drug, the number of platinum‐DNA adducts increased significantly in LLC‐treated insensitive cells. Moreover, the cisplatin content in LDs increased upon LLC treatment. Furthermore, lipid profiles of 22 carcinoma cells with differential cisplatin sensitivity (9 sensitive vs 13 insensitive) were acquired. These profiles revealed low storage lipid levels in insensitive cells. This result recommends that LD lipidome might be a common pathway in multiple cancers for platinum sensitivity in EOC. Finally, LLC suppressed both cisplatin‐insensitive human carcinoma cell training and testing sets. Thus, LDLR‐platinum insensitivity can be due to a defective Lands cycle that hinders LPC production in LDs. Using lipidome assessment with the newly formulated LLC can be a promising cancer chemotherapy method.

Disruption of copper homeostasis is associated with a number of severe diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), Wilson’s disease, and Menkes syndrome. Given this association, the detection and capture of Cu2+ in biological fluids and tissues may provide a new direction for the diagnosis and treatment of related disorders. The current analytical approaches, however, are challenging due to the high cost, complexity, and long time required to prepare and analyze samples. Here, we report a novel salen ligand, namely N,N’-(1,2-phenylene)bis(1-(1H-imidazol-4-yl)methanimine) (pimi), which can readily detect and concurrently capture Cu2+ from aqueous as well as biological mediums. Pimi can selectively and specifically detect Cu2+ from biofluid and cellular samples with rapid ccresponse time (

Platinum-based therapy remains the cornerstone for cancer therapy; however, its efficacy varies. The role of lipoprotein receptor-mediated lipid entry for cancer development has been reported. Yet, the roles and mechanism of the low-density lipoprotein receptor (LDLR) in chemo-sensitivities are unknown. In the current report, we used epithelial ovarian cancer (EOC), composed of various cellularities, to study this issue. Using public cDNA microarray database and single cohort study, LDLR expressions were positively associated with epithelial ovarian carcinomas (EOCs) platinum-based chemotherapy patients’ disease prognosis. In vitro and in vivo add-in/silencing LDLR was introduced to determine cisplatin sensitivity and cancer growth. Results revealed that knocked-down LDLR could sensitize while overexpressed LDLR could insensitize EOC cells to the cytotoxic effects of cisplatin. Moreover, the trans-omics approaches depicted an LDLR→LPC (Lyso-phosphatidylcholine)→FAM83B (phospholipase-related)→FGFRs (cisplatin sensitivity and phospholipase-related) regulatory axis. Finally, the manipulation of LDLR expression in EOC cells was found to determine the efficacy of cisplatin therapy in terms of tumor suppression. In conclusion, the LDLR→LPC→FAM83B→FGFRs axis is an example of tumor macroenvironmental regulation of therapy outcomes. Relatedly, LDLR expression could serve as a biomarker of chemotherapy sensitivity in EOCs. Significance: this study describes the role of LDLR in the development of insensitivity to platinum-based chemotherapy in epithelial ovarian cancer. The lipidome (e.g., LPC) and transcriptome (e.g., FAM38B) interactions revealed using trans-omics approaches an LDLR→LPC→FAM83B→FGFRs regulatory axis in cancer cells, in an animal model, and in patients.

The follow-up data of discharged patients with coronavirus disease 19 (COVID-19) have not yet been fully analyzed and reported. This study aimed to evaluate the clinical features, test results, and outcomes of COVID-19 patients after discharge.149 COVID-19 patients with follow-up data after discharge were included. Post-hospitalization data related to clinical features and outcomes were obtained by following the patients up to 6 weeks.The COVID-19 patients were followed for a median of 28.0 days (range of 22 days to 42 days) after discharge from hospital. At the end of follow-up, four patients (2.7%) still had cough. The proportions of leukopenia and lymphopenia were 7.4% and 4.7%, respectively. The proportions of ALT, AST, and Cr abnormalities were 26.2%, 6.0%, and 0%, respectively. Abnormal chest CT was detected in 94 (63.1%) patients, including 14 (9.4%) unilateral pneumonia and 80 (53.7%) bilateral pneumonia. However, the proportion of chest CT abnormality significantly decreased compared to that at the time of admission.One month after discharge, few patients with COVID-19 had clinical symptoms; however, a substantial proportion of COVID-19 patients harbored abnormal laboratory and radiological examinations. Moderately long-term medical follow-up would justifiably benefit COVID-19 patients after discharge.

To explore the diagnostic performance of EFSUMB CEUS Pancreatic Applications guidelines (version 2017) before and after the addition of iso-enhancement and very fast/fast washout as supplementary diagnostic criteria for PDAC.In this retrospective study, patients diagnosed with solid pancreatic lesions from January 2017 to December 2020 were evaluated. Pancreatic ductal adenocarcinoma (PDAC) is reported to show hypo-enhancement in all phases according to the EFSUMB guidelines. First, based on this definition, all lesions were categorized as PDAC and non-PDAC. Then, iso-enhancement and very fast/fast washout were added as supplementary diagnostic criteria, and all lesions were recategorized. The diagnostic performance was assessed in terms of the accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV). The reference standard consisted of histologic evaluation or composite imaging and clinical follow-up findings.A total of 455 nodules in 450 patients (median age, 58.37 years; 250 men) were included. The diagnostic performance using the EFSUMB CEUS guidelines for PDAC had an ACC of 69.5%, SEN of 65.4%, SPE of 84%, PPV of 93.5%, NPV of 40.6%, and ROC of 0.747. After recategorization according to the supplementary diagnostic criteria, the diagnostic performance for PDAC had an ACC of 95.8%, SEN of 99.2%, SPE of 84%, PPV of 95.7%, NPV of 96.6%, and ROC of 0.916.The EFSUMB guidelines and recommendations for pancreatic lesions can effectively identify PDAC via hypo-enhancement on CEUS. However, the diagnostic performance may be further improved by the reclassification of PDAC lesions after adding iso-enhancement and very fast/fast washout mode.• In the EFSUMB guidelines, the only diagnostic criterion for PDAC is hypo-enhancement, to which iso-enhancement and very fast/fast washout mode were added in our research. • Using hypo-enhancement/iso-enhancement with very fast/fast washout patterns as the diagnostic criteria for PDAC for solid pancreatic masses on CEUS has high diagnostic accuracy. • The blood supply pattern of PDAC can provide important information, and CEUS has unique advantages in this respect due to its real-time dynamic attenuation ability.

Aurora A kinase (Aurora A) is a serine/threonine kinase regulating control of multiple events during cell-cycle progression. Playing roles in promoting proliferation and inhibiting cell death in cancer cells leads Aurora A to become a target for cancer therapy. It is overexpressed and associated with a poor prognosis in ovarian cancer. Improving cisplatin therapy outcomes remains an important issue for advanced-stage ovarian cancer treatment, and Aurora A inhibitors may improve it. In the present study, we identified natural compounds with higher docking scores than the known Aurora A ligand through structure-based virtual screening, including the natural compound fangchinoline, which has been associated with anticancer activities but not yet investigated in ovarian cancer. The binding and inhibition of Aurora A by fangchinoline were verified using cellular thermal shift and enzyme activity assays. Fangchinoline reduced viability and proliferation in ovarian cancer cell lines. Combination fangchinoline and cisplatin treatment enhanced cisplatin–DNA adduct levels, and the combination index revealed synergistic effects on cell viability. An in vivo study showed that fangchinoline significantly enhanced cisplatin therapeutic effects in OVCAR-3 ovarian cancer-bearing mice. Fangchinoline may inhibit tumor growth and enhance cisplatin therapy in ovarian cancer. This study reveals a novel Aurora A inhibitor, fangchinoline, as a potentially viable adjuvant for ovarian cancer therapy.

Previous studies have showed that the apoptosis of vascular smooth muscle cells (VSMCs) underlies the mechanism of pathological calcifications in patients with chronic kidney disease (CKD). SET domain-containing protein 8 (SET8), as an efficient protein has been reported to modulate cell apoptosis in hepatocellular carcinoma cell, esophageal squamous cell and neuronal cell through regulating pathological processes, such as cell-cycle progression and transcription regulation. However, whether SET8 is involved in high phosphorus induced vascular calcification by mediating apoptosis remains undefined. Here, we reported that SET8 was located both in nucleus and cytoplasm, and significantly downregulated in calcification models. SET8 deficiency promoted the apoptosis of VSMCs, which was indicated by the increased Bax/Bcl-2 and cleaved caspase-3/total caspase-3 ratios. Mechanistically, PI3K/Akt pathway was mediated by SET8 and inhibition of PI3K/Akt signaling pathway by giving LY294002 or transfecting Akt phosphorylation inactivated mutation plasmid increased apoptosis and calcification. Akt phosphorylation constitutively activated mutation could reduce apoptosis and calcification of VSMCs. Furthermore, exogenous overexpression of SET8 could reverse the effect of PI3K/Akt inhibition on the apoptosis and calcification of VSMCs. In summary, our researches suggested that SET8 overexpression ameliorated high phosphorus induced calcification of vascular smooth muscle cells via activating PI3K/Akt mediated anti-apoptotic effects.

Gastric cancer (GCa) is a malignancy with few effective treatments. Ursolic acid (UA), a bioactive triterpenoid enriched in Hedyotis diffusa Willd, known to suppress GCa without identified target. CYP19A1 (cytochrome P450 family 19A1; also known as aromatase, Ar) was correlated to GCa prognosis. Relatedly, Ar silencers, which halt the expression of Ar exhibited anti-GCa effects in experimental models, are currently being investigated.The docking simulation score of UA was compared with Ar inhibitors, e.g., letrozole, exemestane, in Ar protein crystallization. Hedyotis diffusa Willd ethanol extract, UA, or 5-fluracil were applied onto AGS, SC-M1, MKN45 GCa cells for cancer inhibition tests. Immunoblot for measuring gene expressions upon drug treatments, or gene knockdown/overexpression. Treatments were also applied in a MKN45 implantation tumor model. A web-based GCa cohort for Ar expression association with prognosis was performed.The ethanol extracts of Hedyotis diffusa Willd, enrich with UA, exhibited cytotoxic activity against GCa cells. Molecular docking simulations with the 3D Ar structure revealed an excellent fitting score for UA. UA increase cytotoxic, and suppressed colony, in addition to its Ar silencing capacity. Moreover, UA synergistically facilitated 5-FU, (a standard GCa treatment) regimen in vitro. Consistent with those results, adding estradiol did not reverse the cancer-suppressing effects of UA, which confirmed UA acts as an Ar silencer. Furthermore, UA exhibited tumor-suppressing index (TSI) score of 90% over a 6-week treatment term when used for single dosing in xenograft tumor model. In the clinical setting, Ar expression was found to be higher in GCa tumors than normal parental tissue from the TCGA (The Cancer Genome Atlas) cohort, while high Ar expression associated with poor prognosis. Together, the results indicate UA could be used to treat GCa by silencing Ar expression in GCa. Hedyotis diffusa Willd ethanol extract could be an functional food supplements.

ObjectivesTo screen out the predictors of central cervical lymph node metastasis (CLNM) for papillary thyroid carcinoma (PTC) and establish a prediction model to guide the operation of PTC patients (cN0).MethodsData from 296 PTC patients (cN0) who underwent thyroid operation at the Second Affiliated Hospital of Chongqing Medical University were collected and retrospectively analyzed. They were divided into two groups in accordance with central CLNM or not. Their information, including ultrasound (US) features, BRAFV600E status, and other characteristics of the two groups, was analyzed and compared using univariate and multivariate logistic regression analyses, and the independent predictors were selected to construct a nomogram. The calibration plot, C-index, and decision curve analysis were used to assess the prediction model’s calibration, discrimination, and clinical usefulness.ResultsA total of 37.8% (112/296) of PTC patients had central CLNM, and 62.2% (184/296) did not. The two groups were compared using a univariate logistic regression analysis, and there were no significant differences between the two groups in sex, aspect ratio, boundary, morphology, hypoechoic nodule, thyroid peroxidase antibody, or tumor location (P>0.05), and there were significant differences between age, tumor size, capsule contact, microcalcifications, blood flow signal, thyroglobulin antibodies (TgAb), and BRAF gene status (PConclusionIn conclusion, three independent predictors of central CLNM, including tumor size (> 1.0 cm), US features (microcalcifications), and TgAb (positive), were screened out. A visualized nomogram model was established based on the three predictors in this study, which could be used as a basis of central cervical lymph node dissection (CLND) for PTC patients (cN0).

Background In 2016, the government of Bao’an District, Shenzhen, China launched a free medication program for all non-registered permanent residents with severe mental disorders (SMD) within its jurisdiction, in efforts to reduce the relapse caused by intermittent medication or non-medication. Participation in the program has not been analyzed since its inauguration. This study aimed to evaluate the participation of non-registered permanent residents with SMD in the program from 2016 to 2020 and to explore its influencing factors. Methods This is a retrospective cross-sectional study of 3760 non-registered permanent residents with SMD in Bao’an District, Shenzhen, China (response rate: 78.64%). Data have been obtained from two sources: the Shenzhen Information System for Psychosis in 2020 and the free medication program’s management files from 2016 to 2020. We employ descriptive statistics to analyze the participation rate of the free medication program among non-registered permanent patients. Logistic regression analysis is used to explore the factors affecting the patients’ participation in the program. Results The participation rate of the free medication program among non-registered permanent patients has shown an upward trend, rising from 28.83% in 2016 to 58.32% in 2020. High participation rates have been registered among the following patient subgroups: those aged between 30 and 39 (63.11%), those with high school/technical secondary school (62.33%), those from rural areas (61.62%), those living in poverty (67.79%), those suffering schizoaffective disorder (72.26%), those having SMD for less than 5 years (59.89%), and those with family history of mental illness (71.23%).Logistics regression analysis shows that age, patient-guardian relationship, place of residence, financial condition, types of disease, duration of illness and family history are the main factors affecting the patients’ decision to participate in the free medication program. Conclusion The steadily increasing participation rate of the free medication program indicates that the program has been gradually accepted and recognized by non-registered permanent residents with SMD. However, nearly half of the patients have yet to join the program. To further raise the participation rate, special attention should be given to patients who are financially secure, aged below 20, without guardians, intellectually disabled or suffering SMD for over 5 years.

Methadone maintenance treatment (MMT) remains the cornerstone for the management of opiate abuse. However, MMT can be associated with complex factors, including complications during the tolerance phase, the inability of some patients to maintain treatment effects during the tapering or abstinence phases, and the development of methadone dependence. Previous studies have revealed a sex disparity in MMT efficacy, showing that women undergoing MMT experiencing an increase in psychological symptoms compared with men and suggesting a link between disparate responses and the effects of estrogen signaling on methadone metabolism. More specifically, estradiol levels are positively associated with MMT dosing, and the expression of a single-nucleotide polymorphism (SNP) associated with estrogen receptor (ER) regulation is also associated with MMT dosing. In addition to performing mechanistic dissections of estrogen signaling in the presence of methadone, past studies have also proposed the targeting of estrogen signaling during MMT. The present report provides an overview of the relevant literature regarding sex effects, including differences in sex hormones and their potential impacts on MMT regimens. Moreover, this article provides a pharmacological perspective on the targeting of estrogen signals through the use of selective ER modulators (SERMs) during MMT. Preliminary preclinical experiments were also performed to evaluate the potential effects of targeting estrogen signaling with tamoxifen on methadone metabolism.

Multimodal general anesthesia based on modified intercostal nerve block (MINB) has been found as a novel method to achieve an intraoperative opioid-sparing effect. However, there is little information about the effective method to inhibit visceral nociceptive stress during single-port thoracoscopic surgery.To investigate whether a low-dose dexmedetomidine infusion followed by MINB might be an alternative method to blunt visceral stress effectively.Double-blind, randomized control trial.Affiliated hospital from March 2020 through September 2020.Fifty-four patients were randomized (1:1), 45 patients were included to receive dexmedetomidine with a 0.4 microgram/kg bolus followed by 0.4 microgram/kg/h infusion (group Dex) or saline placebo (group Con). During the operation, an additional dose of remifentanil 0.05-0.25 microgram/kg/min was used to keep mean arterial pressure (MAP) or heart rate (HR) values around 20% below baseline values. The primary outcome was to evaluate remifentanil consumption. Secondary outcomes included intraoperative hemodynamics, the first time to press an analgesia pump, and adverse effects.Remifentanil consumption during surgery was markedly decreased in the Dex group than in the Con group (0 [0-0] versus 560.0 [337.5-965.0] microgram; P = 0.00). MAP and HR in the Con group during the first 5 minutes after visceral exploration was significantly higher than in the Dex group (P0.05). Time to first opioid demand was significantly prolonged (P = 0.04) and postoperative length of stay was shortened slightly in the Dex group (P = 0.05).This study was limited by the measurement of nociception.This study demonstrates that low-dose dexmedetomidine infusion combined with MINB might be an effective alternative method to blunt visceral stress in patients undergoing single-port thoracoscopic lobectomy. Furthermore, the analgesic effect of MINB was significantly prolonged after dexmedetomidine infusion.

Aurora kinase A (AURKA) carries out an essential role in proliferation and involves in cisplatin resistance in various cancer cells. Overexpression of AURKA is associated with the poor prognosis of cancer patients. Thus, AURKA has been considered as a target for cancer therapy. Developing AURKA inhibitors became an important issue in cancer therapy. A natural compound emodin mainly extracted from rhubarbs possesses anti-cancer properties. However, the effect of emodin on AURKA has never been investigated. In the present study, molecular docking analysis indicated that emodin interacts with AURKA protein active site. We also found nine emodin analogues from Key Organic database by using ChemBioFinder software. Among that, one analogue 8L-902 showed a similar anti-cancer effect as emodin. The bindings of emodin and 8L-902 on AURKA protein were confirmed by cellular thermal shift assay. Furthermore, emodin inhibited the AURKA kinase activity in vitro and enhanced the cisplatin-DNA adduct level in a resistant ovarian cancer cell line. It seems that emodin may have the potential to inhibit cancer cell growth and enhance cisplatin therapy in cancer with resistance. Collectively, our finding reveals a novel AURKA inhibitor, emodin, which may be vulnerable to ovarian cancer therapy in the future.

Cardiovascular disease (CVD) is one of the most serious diseases threatening human health. Arterial blood pressure (ABP) waveforms, containing vivid cardiovascular information, are of great significance for the diagnosis and the prevention of CVD. This paper proposes a deep learning model, named ABP-Net, to transform photoplethysmogram (PPG) signals into ABP waveforms that contain vital physiological information related to cardiovascular systems. In order to guarantee the quality of the predicted ABP waveforms, the structure of the network, the input signals and the loss functions are carefully designed. Specifically, a Wave-U-Net, one kind of fully convolutional neural networks (CNN), is taken as the core architecture of the ABP-Net. Besides the original PPG signals, its first derivative and second derivative signals are all utilized as the inputs of the ABP-Net. Additionally, the maximal absolute loss, accompany with the mean squared error loss is employed to ensure the match of the predicted ABP waveform with the reference one. The performance of the proposed ABP network is tested on the public MIMIC II database both in subject-dependent and subject-independent manners. Both results verify the superior performance of the proposed model over those existing methods accordingly. The mean absolute error (MAE) and the root-mean-square error (RMSE) between the predicted waveforms via the ABP-Net and the reference ones are 3.20 mmHg and 4.38 mmHg during the subject-dependent experiments while those are 5.57 mmHg and 7.15 mmHg during the subject-independent experiments. Benefiting from the predicted high-quality ABP waveforms, more ABP related physiological parameters can be better obtained, which effectively expands the application scope of PPG devices.

Background There is still little knowledge about the association of liver fibrosis with the clinical outcomes of COVID‐19 patients with non‐alcoholic fatty liver disease (NAFLD). The aim of the study was to determine the association of NAFLD fibrosis score (NFS)–determined liver fibrosis with clinical outcomes of COVID‐19 patients with NAFLD. Methods The NAFLD was diagnosed by the Hepatic Steatosis Index (HSI) in the absence of other causes of chronic liver diseases. NFS was used to evaluate the severity of liver fibrosis. Results A total of 86 COVID‐19 patients with NAFLD were included. The median age was 43.5 years, and 58.1% of patients were male. Thirty‐eight (44.2%) patients had advanced liver fibrosis according to the NFS. Multivariate analysis indicated that concurrent diabetes (odds ratio [OR] 8.264, 95% confidence interval [CI] 1.202–56.830, p = 0.032) and advanced liver fibrosis (OR 11.057, 95% CI 1.193–102.439, p = 0.034) were independent risk factors of severe illness in COVID‐19 patients with NAFLD. Conclusion NAFLD patients with NFS‐determined advanced liver fibrosis are at higher risk of severe COVID‐19., Concurrent with NAFLD is common in COVID‐19 patients. The presence of advanced liver fibrosis was an independent risk factor of severe illness in COVID‐19 patients with NAFLD.

Background The clinical and virological course of patients with coronavirus disease 2019 (COVID-19) are lacking. We aimed to describe the clinical and virological characteristics of COVID-19 patients from 10 designated hospitals in 10 cities of Jiangsu province, China. The factors associated with the clearance of SARS-CoV-2 were investigated. Methods A total of 328 hospitalized patients with COVID-19 were retrospectively recruited. The epidemiological, clinical, laboratory, radiology and treatment data were collected. The associated factors of SARS-CoV-2 clearance were analyzed. Results The median duration of hospitalization was 16.0 days (interquartile range [IQR] 13.0–21.0 days). On multivariate Cox regression analysis, age > 60 years (hazard ratio [HR] 0.643, 95% confidence interval [CI] 0.454–0.911, P = 0.013) was associated with the delayed SARS-CoV-2 clearance, while the atomized inhalation of interferon α-2b could improve the clearance of SARS-CoV-2 (HR, 1.357, 95% CI 1.050–1.755, P = 0.020). Twenty-six (7.9%) patients developed respiratory failure and 4 (1.2%) patients developed ARDS. Twenty (6.1%) patients were admitted to the ICU, while no patient was deceased. Conclusions Our study found that age > 60 years was associated with the delayed SARS-CoV-2 clearance, while treated with atomized inhalation of interferon α-2b could promote the clearance of SARS-CoV-2.

A highly diastereoselective method for the synthesis of novel spiro-tetrahydroquinoline derivatives is reported here, using a one-pot reaction method. All compounds were characterized by 1H-nuclear magnetic resonance (NMR) and mass spectroscopy, and their stereo configurations were confirmed by X-ray analysis. These activities of these derivatives were then tested in human keratocyte cells. The responses of cells to treatment with selected compounds were studied using scratch analysis, and the compounds were tested in a mouse excision wound model. Three of the derivatives demonstrated significant wound-healing activities.

CYP19A1/aromatase (Ar) is a prognostic biomarker of gastric cancer (GCa). Ar is a critical enzyme for converting androstenedione to oestradiol in the steroidogenesis cascade. For decades, Ar has been targeted with Ar inhibitors (ARIs) in gynaecologic malignancies; however, it is unexplored in GCa. A single‐cohort tissue microarray examination was conducted to study the association between Ar expression and disease outcome in Asian patients with GCa. The results revealed that Ar was a prognostic promoter. Bioinformatics analyses conducted on a Caucasian‐based cDNA microarray databank showed Ar to be positively associated with GCa prognosis for multiple clinical modalities, including surgery, 5‐Fluorouracil (5‐FU) for adjuvant chemotherapy, or HER2 positivity. These findings imply that targeting Ar expression exhibits a potential for fulfilling unmet medical needs. Hence, Ar‐targeting compounds were tested, and the results showed that exemestane exhibited superior cancer‐suppressing efficacy to other ARIs. In addition, exemestane down‐regulated Ar expression. Ablating Ar abundance with short hairpin (sh)Ar could also suppress GCa cell growth, and adding 5‐FU could facilitate this effect. Notably, adding oestradiol could not prevent exemestane or shAr effects, implicating a nonenzymatic mechanism of Ar in cancer growth. Regarding translational research, treatment with exemestane alone exhibited tumour suppression efficacy in a dose‐dependent manner. Combining subminimal doses of 5‐FU and exemestane exerted an excellent tumour suppression effect without influencing bodyweight. This study validated the therapeutic potentials of exemestane in GCa. Combination of metronomic 5‐FU and exemestane for GCa therapy is recommended.

N,N-Dimethylformamide (DMF) is a widespread contaminant of leather factories and their surrounding environment. There is a lack of direct in vivo evidence supporting CYP2E1 as a primary enzyme responsible for DMF metabolism and hepatotoxicity. In this study, a novel Cyp2e1 knockout (KO) mouse model was generated and used to assess whether DMF metabolism and hepatotoxicity is CYP2E1 dependent using an acute toxicity protocol with a single dose of 1500 mg DMF/kg. An epidemiological study in 698 DMF-exposed workers and 188 non-DMF-exposed controls was conducted to investigate the associations between functional polymorphisms of CYP2E1 (rs6413432/rs2031920) and DMF metabolite (N-methylcarbmoylated-hemoglobin [NMHb]). We successfully established Cyp2e1 KO mice with evidence from DNA sequence analysis, which showed 1-bp insertion at 65 bp (C) site of Cyp2e1 Exon 1. In addition, western blot and in vivo pharmacokinetic study also showed a complete absence of CYP2E1 protein and a 92% and 88% reduction in CYP2E1 activity among males and females, respectively. DMF metabolism as evidenced by increased blood NMHb, and hepatotoxicity as evidenced by elevated liver/body weight ratio, activity of liver enzymes and massive liver necrosis were detected in wild-type (WT) mice but were completely abrogated in KO mice, strongly supporting a CYP2E1-dependent pattern of DMF metabolism and hepatotoxicity. Moreover, variant allele of CYP2E1-rs6413432 was also significantly associated with higher NMHb levels in DMF-exposed workers (P = 0.045). The increase of glucose-regulated protein 94 detected in WT mice but not in KO mice suggested CYP2E1-dependent endoplasmic reticulum stress may be a key mechanism underlying DMF-induced hepatotoxicity.

The soluble amyloid protein procurer α (sAPPα) and β (sAPPβ) have been postulated as promising new cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) and multiple other neurodegenerative diseases, but have failed to meet expectations with their often discordant and even contradictory findings to date. The aim of the study was to systematically explore this issue. Cochrane Library, PubMed, and CNKI were systematically searched without language or date restrictions. This network meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and also adhered to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Twenty studies, comprising ten groups, were eligible and included. Overall, 19 eligible studies with 1634 patients contributed to the analysis of CSF sAPPα levels and 16 eligible studies with 1684 patients contributed to the analysis of CSF sAPPβ levels. CSF sAPPβ levels are significantly higher in AD than in corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP); higher in Control than in Depression, CBS and PSP; higher in Parkinson's disease dementia (PDD) than in CBS and PSP; higher in mild cognitive impairment progressed to AD dementia during the follow-up period (pMCI) than in Depression and PSP; higher in stable mild cognitive impairment (sMCI) than in Depression. With regard to CSF sAPPα levels, there were no significant difference among groups. However, surprisingly, the resultant rankings graphically showed that pMCI populations have the highest levels of CSF sAPPα and sAPPβ. Furthermore, it seemed there was a positive correlation between CSF sAPPα and sAPPβ levels. The measurement of CSF sAPPα and sAPPβ levels may provide an alternative method for the diagnosis of early-stage AD, pMCI, which is conducive to preventive therapy.

Bone marrow‑derived mesenchymal stem cells (MSCs), are the basic cellular components that make up the bone marrow microenvironment (BMM). In acute myeloid leukemia (AML), the morphology and function of MSCs changes in accordance with the transformation of the BMM. Moreover, the transformation of MSCs into osteoblasts is determined through the bone morphogenetic protein (BMP) pathway, ultimately leading to an altered expression of the downstream adhesion molecule, connective tissue growth factor (CTGF). In this study, we aimed to explore the interaction of possible pathways in AML‑derived mesenchymal stem cells (AML‑MSCs) co‑cultured with the K562 and K562‑ADM cell lines. AML‑MSCs were co‑cultured with K562/K562‑ADM cells, and the interactions between the cells were verified by morphological detection, peroxidase staining (POX), reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and fluorescence in situ hybridization (FISH). The proliferation of K562/K562‑ADM cells under co‑culture conditions was detected by flow cytometry. The expression levels of BMP4 and CTGF were examined by RT‑qPCR and western blot (WB) analysis. The detection of interleukin (IL)‑6 and IL‑32 was also determined by enzyme linked immunosorbent assay (ELISA). In the co‑culture system, the K562‑ADM cells underwent fusiform transformation. The occurrence of this transformation was associated with an increased expression of CTGF due to the dysregulation of the BMP pathway. The AML‑MSCs promoted the proliferation of the K562‑ADM cell, but inhibited that of the K562 cells. These findings were confirmed by changes in the expression of the soluble cytokines, IL‑6 and IL‑32. On the whole, the findings of this study demonstrate that AML‑MSCs regulate the expression of CTGF through the BMP pathway. In addition, they affect cytokine production, induce spindle‑shaped transformation, and increase drug resistance in the K562‑ADM cells. Thus, the morphological transformation through the BMP pathway provides us with a novel target with which to circumvent tumor occurrence, development, drug resistance, invasion and metastasis.

Bone age assessment (BAA) has various clinical applications such as diagnosis of endocrine disorders and prediction of final adult height for adolescents. Recent studies indicate that deep learning techniques have great potential in developing automated BAA methods with significant advantages over the conventional methods based on handcrafted features. In this paper, we propose a multi-scale data fusion framework for bone age assessment with X-ray images based on non-subsampled contourlet transform (NSCT) and convolutional neural networks (CNNs). Unlike the existing CNN-based BAA methods that adopt the original spatial domain image as network input directly, we pre-extract a rich set of features for the input image by performing NSCT to obtain its multi-scale and multi-direction representations. This feature pre-extraction strategy could be beneficial to network training as the number of annotated examples in the problem of BAA is typically quite limited. The obtained NSCT coefficient maps at each scale are fed into a convolutional network individually and the information from different scales are then merged to achieve the final prediction. Specifically, two CNN models with different data fusion strategies are presented for BAA: a regression model with feature-level fusion and a classification model with decision-level fusion. Experiments on the public BAA dataset Digital Hand Atlas demonstrate that the proposed method can obtain promising results and outperform many state-of-the-art BAA methods. In particular, the proposed approaches exhibit obvious advantages over the corresponding spatial domain approaches (generally with an improvement of more than 0.1 years on the mean absolute error), showing great potential in the future study of this field.

Objectives The primary aim of this study was to determine if computed tomographic (CT) texture analysis measurements of the tumor are independently associated with progression-free survival (PFS) and overall survival (OS) in patients with unresectable pancreatic ductal adenocarcinoma (PDAC), including both unresectable locally advanced and metastatic PDAC, who were treated with chemotherapy. Methods After an institutional review board waiver was obtained, contrast material-enhanced CT studies in 41 patients with unresectable PDAC who underwent contrast-enhanced CT before chemotherapy between 2014 and 2017 were analyzed in terms of tumor texture, with quantification of mean gray-level intensity (Mean), entropy, mean of positive pixels (MPP), kurtosis, standard deviation (SD), and skewness for fine to coarse textures (spatial scaling factor (SSF) 0–6, respectively). The association between pretreatment and posttreatment texture parameters, as well as Δ value (difference between posttreatment and pretreatment texture parameters), and survival time was assessed by using Cox proportional hazards models and Kaplan-Meier analysis. Results Findings from the multivariate Cox model indicated that tumor size, tumor SD (HR, 0.942; 95% CI: 0.898, 0.988) and skewness (HR, 0.407; 95% CI: 0.172, 0.962) measurements with SSF = 3, and tumor SD (HR, 0.958; 95% CI: 0.92, 0.997) measurements with SSF = 4 were significantly and independently associated with PFS, while tumor size and tumor SD (HR, 0.928; 95% CI: 0.882, 0.976) measurements with SSF = 3 were significantly and independently associated with OS. None of the post-therapy texture parameters or Δ value had a significant association with OS or PFS in multivariate Cox regression models. Medium SD (SSF = 3) of more than 38.38 and coarse SD (SSF = 4) of more than 40.67 were associated with longer PFS after chemotherapy (for SSF = 3, median PFS was 10.0 vs 6.0 months [P = 0.024], and for SSF = 4, median PFS was 12.0 vs 6.0 months [P = 0.003]). SD of 38.38 or greater (SSF = 3) as a dichotomized variable was a significant positive prognostic factor for OS (median OS, 20.0 vs 9.0 months [P = 0.04]). Survival models that included a combination of pretreatment SD (SSF = 3) with tumor size, had the potential to perform better than SD alone, while having no statistical significance in this study (area under the ROC curve, 0.756 vs 0.715 [P = 0.066]). Conclusions Pretreatment CT quantitative imaging biomarkers from texture analysis are associated with PFS and OS in patients with unresectable PDAC who were treated with chemotherapy, and the combination of pretreatment texture parameters and tumor size have the potential to perform better in survival models than imaging biomarker alone.

Gesture recognition based on surface electromyogram (sEMG) signals has drawn significant attention and obtained satisfactory achievement in the field of human-computer interaction. However, the same gesture performed with different arm positions tends not to generate the same sEMG signals. Traditional solutions can be divided into two types. One type treats the same gesture with different arm positions as the same type, leading to a relatively low classification rate. The other type adopts a gesture classifier followed by the position classifier, which will achieve a satisfactory classification accuracy but at the expenses of high training burdens. To address these issues, we propose a novel framework to explore the intrinsic position independent (PI) characteristics of sEMG signals generated from the same gesture with different arm positions by canonical correlation analysis (CCA), termed as PICCA. In this framework, with the bridge link of the predefined expert set, both the training set and the testing set can be mapped into a unified-style with CCA, and hence, the classification accuracy can be improved in both user-dependent and user-independent manners. Experimental results on 13 gestures with 3 arm positions indicate that the proposed PICCA can achieve higher classification rates than those without CCA (with 28.52% and 44.19% promotions during user-dependent and user-independent manners respectively) while maintaining acceptable training burdens. These improvements will facilitate the practical implementation of myoelectric interfaces.

This paper depicted the whole-course care for an advanced cancer patient from hospital to home.In this case,telemedicine was employed to provide guidance on the symptom control,comfort care,psychotherapy,and bereavement counseling.The patient got the holistic care from the whole family and team.The holistic care finally gave a good death of the patient and aided in the recovery of the family members from grief.

Surgical wounds are common injuries of skin and tissues and usually become a clinical problem. Until now, various synthetic and natural peptides have been widely explored as potential drug candidates for wound healing. Inhibition of the TNF-α signaling pathway and promotion of angiogenesis are suggested to be involved in their effects. Angiogenesis at the wound site is one of the essential requisites for rapid healing. In the present study, a novel peptide extract derived from the natural source Lates calcarifer, commonly known as sea bass or barramundi, was evaluated for its wound healing property. The specific acidic and enzymatic approaches were employed for producing sea bass extract containing small size peptides (molecular weight ranging from 1 kD to 5 kD). The cytotoxicity of the extract was examined in HaCaT and NIH3T3. After this, the effects of enzyme digested peptide extracts of sea bass on wound healing in mice were investigated. The peptide extracts (660 and 1320 mg/kg/day) and control protein (1320 mg/kg/day) was orally given to the wounded mice, respectively, for 12 days. The surgical method was improved by implanting a silicone ring at the wound site. The ring avoided the contracting effect in murine wounds, making it more closely related to a clinical condition. The results showed promising improvement at the wound site in mice. Sea bass peptide extracts accelerated the wound healing process and enhanced the microvessel formation at the wound site. The remarkable effects of this novel sea bass peptide extract in healing traumatic injuries revealed a new option for developing wound management.

High-throughput screening facilitates the rapid identification of novel hit compounds; however, it remains challenging to design effective high-throughput assays, partially due to the difficulty of achieving sensitivity in the assay techniques. Among the various analytical methods that are used, fluorescence-based assays dominate due to their high sensitivity and ease of operation. Recent advances in activity-based sensing/imaging have further expanded the availability of fluorescent probes as monitors for high-throughput screening of result outputs. In this study, we have reviewed various activity-based fluorescent probes used in high-throughput screening assays, with an emphasis on their structure-related working mechanisms. Moreover, we have explored the possibility of developing additional and better probes to boost hit identification and drug development against various targets.

AML is the most common blood cancer in adults with a high relapse and an overall poor survival rate. NK cells have been demonstrated to have the capacity to eradicate AML blast, and an impaired NK cell function is involved in AML development and progression. Immune checkpoints are involved in immune escape in various cancers. Immune checkpoints blockade therapy mainly aimed to unleash CD8+T cells function, but NK cells have emerged as new target. However, immune checkpoints profile on NK cells has not been observed in AML patients. Here, we studied the immune checkpoints expression of NK cells from AML patients at initial diagnosis and found increased PD-1, TIGIT and TIM-3 expression compared to NK cells from healthy donors. Further analysis showed that TIGIT expressing NK cells from AML patients had a dysfunctional phenotype, as TIGIT+NK cells exhibit lower antileukemia effect, cytokine production and degranulation compared to TIGIT-NK cells. TIGIT blockade could significantly enhance the function of NK cells. Moreover, AML patients with high frequency of TIGIT+NK cells had higher frequency of poor prognosis risk. Further analysis found that IL-10 upregulated TIGIT expression on NK cells. Thus, TIGIT blockade alone or in combination with other therapy might be potential strategy to treat AML.

Background Hematological comparison of coronavirus disease (COVID-19) and other viral pneumonias can provide insights into COVID-19 treatment. Methods In this retrospective case–control single-center study, we compared the data of 126 patients with viral pneumonia during different outbreaks [severe acute respiratory syndrome (SARS) in 2003, influenza A (H1N1) in 2009, human adenovirus type 7 in 2018, and COVID-19 in 2020]. Results One of the COVID-19 characteristics was a continuous decline in the hemoglobin level. The neutrophil count was related to the aggravation of COVID-19 and SARS. Thrombocytopenia occurred in patients with SARS and severe COVID-19 even at the recovery stage. Lymphocytes were related to the entire course of adenovirus infection, recovery of COVID-19, and disease development of SARS. Conclusions Dynamic changes in hematological counts could provide a reference for the pathogenesis and prognosis of pneumonia caused by respiratory viruses in clinics.

We aimed to describe liver injury and identify the risk factors of liver injury in coronavirus disease (COVID-19) patients without chronic liver diseases (CLD). The clinical data of 228 confirmed COVID-19 patients without CLD were retrospectively collected from ten hospitals in Jiangsu, China. Sixty-seven (29.4%) of 228 patients without CLD showed abnormal liver function on admission, including increased alanine aminotransferase (ALT) (25 [11.0%]) U/L, aspartate aminotransferase (AST) 30 [13.2%]) U/L, gamma-glutamyl transferase (GGT) 28 [12.4%]) U/L, total bilirubin (Tbil) 16 [7.0%] µmol/L, and alkaline phosphatase (ALP) 10 [4.5%]) U/L. During hospitalization, 129 (56.3%) of 228 patients showed abnormal liver function, including elevated ALT (84 [36.8%]), AST (58 [25.4%]), GGT (67 [29.5%]), and Tbil (59 [25.9%]). Age over 50 years (odds ratio [OR], 2.086; 95% confidence interval [CI], 1.030-4.225; p = .041), male sex (OR, 2.737; 95% CI, 1.418-5.284; p = .003), and lopinavir-ritonavir (OR, 2.504; 95% CI, 1.187-5.283; p = .016) were associated with higher risk of liver function abnormality, while the atomized inhalation of interferon α-2b (OR, 0.256; 95% CI 0.126-0.520; p < .001) was associated with reduced risk of liver function abnormality during hospitalization. Mild to moderate liver injury was common in COVID-19 patients in Jiangsu, China. Age over 50 years, male sex, and lopinavir-ritonavir were the independent risk factors of liver impairment in COVID-19 patients during hospitalization.

BackgroundTuberculosis (Tb) is the most frequent opportunistic infection among people living with HIV infection. The impact of Tb co-infection in the establishment and maintenance of the HIV reservoir is unclear.MethodWe enrolled 13 HIV-infected patients with microbiologically confirmed Tb and 10 matched mono-HIV infected controls. Total HIV DNA in peripheral blood mononuclear cells (PBMCs), plasma interleukin-7 (IL-7) concentrations and the activities of indoleamine 2,3-dioxygenase (IDO) were measured for all the participants prior to therapy and after antiretroviral therapy (ART).ResultsAfter a duration of 16 (12, 22) months’ ART, patients co-infected with Tb who were cured of Tb maintained higher levels of HIV DNA compared with mono-HIV infected patients [2.89 (2.65- 3.05) log10copies/106cells vs. 2.30 (2.11–2.84) log10copies/106cells,P = 0.008]. The levels of on-ART HIV DNA were positively correlated with the baseline viral load (r = 0.64,P = 0.02) in Tb co-infected group. However, neither plasma IL-7 concentration nor plasma IDO activity was correlated with the level of on-ART HIV DNA.ConclusionsTb co-infection was associated with the increased surrogate marker of the HIV reservoir, while its mechanism warrants further examination.