Efficacy and safety of combination of ulinastatin and meglumine cyclic adenosine monophosphate in the treatment of acute myocardial infarction, and its effect on serum levels of hs-CRP, cTnI and CK

Purpose: To determine the efficacy and safety of a combination of ulinastatin and meglumine cyclic adenosine monophosphate (cAMP) in the treatment of acute myocardial infarction (AMI), and its effect on serum levels of hypersensitive-c-reactive protein (hs-CRP), cardiac troponin I (cTnI), creatine kinase (CK).Methods: A total of 90 AMI patients admitted to The Second Affiliated Hospital of Qiqihar Medical College, Qiqihar City, Heilongjiang Province, China from January 2019 to January 2020 were selected and randomized (in a 1:1 ration) into control group and study group. Patients in the two groups received meglumine cAMP, while those in the study group were, in addition, treated with ulinastatin. The two groups were compared with regard to clinical efficacy, cardiac function indices, serum biochemical indices, incidence of drug-related side effects, duration and number of episodes of angina pectoris, and levels of neuroendocrine hormones.Results: The study group exhibited remarkably higher treatment effectiveness and cardiac function indices compared to the control group (p < 0.05). However, lower levels of serum biochemical indices, lower total incidence of drug toxicity, smaller number and shorter duration of angina pectoris, and lower levels of panel reactive antibodies (PRA) were observed in the study when compared to control group (p< 0.001).Conclusion: Treatment of AMI patients with the combination of ulinastatin and meglumine cAMP significantly reduces the clinical symptoms of the patients, with remarkable efficacy and high safety. Furthermore, it down-regulates serum levels of hs-CRP, cTnI and CK. Thus, the combination treatment seems superior to the conventional therapy

Sorafenib modulates the radio sensitivity of hepatocellular carcinoma cells in vitro in a schedule-dependent manner

BACKGROUND: Hepatocellular carcinoma (HCC) has a high incidence and mortality. Radiotherapy and sorafenib have proven effective for HCC. Here, we investigated whether sorafenib modulated the response of HCC cells to irradiation in vitro, effect of timing of sorafenib, and the underlying mechanisms. METHODS: Cell viability of the HCC cell lines, SMMC-7721 and Bel-7402, was examined by the 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2(4-sulfophenyl)-2 H-terazolium (MTT) assays. Clonogenic growth assays of SMMC-7721 and Bel-7402 were determined by colony formation assays. DNA damage was assessed by monitoring γ-HAX foci in irradiated cells with immunofluorescence microscopy, and cell cycle distribution changes were examined by flow cytometry. Effects of sorafenib (15 μM) added 30 min prior to radiation (pre-irradiation sorafenib) of SMMC-7721 and BEL-7402 or 24 h post-irradiation (post-irradiation sorafenib) on irradiated SMMC-7721 and BEL-7402 cells were compared to those of radiation alone or no treatment. RESULTS: The effect of sorafenib was dependent on its time of addition in relationship to irradiation of cells. Pre-irradiation sorafenib did not significantly affect the viability of SMMC-7221 and BEL-7402 cells compared with irradiation treatment alone. In contrast, post-irradiation sorafenib increased the sensitivity of irradiated SMMC-7221 and BEL-7402 cells significantly in a time-dependent manner. Pre-irradiation sorafenib significantly increased the surviving fraction of SMMC-7221 and BEL-7402 cells in clonogenic assays whereas post-irradiation sorafenib significantly reduced the surviving fractions of SMMC-7221 and BEL-7402 cells. SMMC-7721 cells treated with sorafenib 30 min before irradiation had significantly fewer cells with γ-H2AX foci (23.8 ± 2.9%) than SMMC-7721 cells receiving radiation alone (59.9 ± 2.4; P < 0.001). Similarly, BEL-7402 cells receiving sorafenib prior to irradiation had significantly fewer cells with γ-H2AX foci (46.4 ± 3.8%) than those receiving radiation alone (25.0 ± 3.0%; P < 0.001). In addition, irradiation (6 Gy) caused a significant increase in the percentage of both SMMC-7721 and BEL-7402 cells in G2/M at 12 to 16 h post irradiation, which was markedly delayed by pre-irradiation sorafenib. CONCLUSIONS: Sorafenib combined with irradiation exerted a schedule-dependent effect in HCC cells in vitro, which has significant implications for the combined use of sorafenib and radiotherapy for HCC patients

Coding the negative emotions of family members and patients among the high-risk preoperative conversations with the Chinese version of VR-CoDES

Abstract Background Little is known about family members' and patients' expression of negative emotions among high‐risk preoperative conversations. Objectives This study aimed to identify the occurrence and patterns of the negative emotions of family members and patients in preoperative conversations, to investigate the conversation themes and to explore the correlation between the negative emotions and the conversation themes. Methods A retrospective study was conducted using the Chinese version of Verona Coding Definitions of Emotional Sequences (VR‐CoDES‐C) to code 297 conversations on high‐risk procedures. Inductive content analysis was used to analyse the topics in which negative emotions nested. The χ2 Test was used to test the association between the cues and the conversation themes. Results The occurrence rate of family members' and patients' negative emotions was very high (85.9%), much higher when compared to most conversations under other medical settings. The negative emotions were mainly expressed by cues (96.4%), and cue‐b (67.4%) was the most frequent category. Cues and concerns were mostly elicited by family members and patients (71.6%). Negative emotions were observed among seven themes, in which ‘Psychological stress relating to illness severity, family's care and financial burden’ (30.3%) ranked the top. Cue‐b, cue‐c and cue‐d had a significant correlation (p < .001) with certain themes. Conclusions Family members and patients conveyed significantly more negative emotions in the high‐risk preoperative conversations than in other medical communications. Certain categories of cues were induced by specific emotional conversation contents. Patient Contribution Family members and patients contributed to data

Tumor characteristics and surgical outcome in incidentally discovered pheochromocytomas and paragangliomas

Objective: The proportion of incidentally discovered pheochromocytomas and paragangliomas (PPGL) has increased over time. However, our knowledge of them is quite limited. The purpose of this retrospective study is to generalize the commonalities in incidentally discovered PPGL, offer evidence for clinical diagnosis and management. Methods: Five hundred twenty-six patients were included in our study after filtration from the database of West China Hospital of Sichuan University between May, 2007 and December, 2016. Among the patients, 148 of them were incidental findings and 378 of them were suspected findings. All patients’ demography and tumor characteristics were recorded in detail, especially hemodynamic records and hormonal assays. The reasons for taking radiography were also collected. Most patients received preoperative medical preparation. Intraoperative and postoperative courses as well as surgical outcomes were also analyzed to identify differences between incidental findings and suspected findings. Results: Incidentally discovered PPGL took up 28.1% of the study population. Suspected PPGLs had a higher prevalence of hypertension, lower proportion of non-functioning PPGL, higher prevalence of MEN2 and better post-surgical blood pressure recovery than incidental finding group. However, patients in the incidental finding group showed no significant difference in preoperative blood pressure and hormonal assays with suspected findings in metaphrine and normetaphrine in plasma and urine (P > 0.05). Conclusions: Due to the development of technology, more PPGLs are discovered incidentally. Considering the tumor characteristics and surgical outcome, surgical decisions should be made more cautiously

The emerging nanomedicine-based technology for non-small cell lung cancer immunotherapy: how far are we from an effective treatment

Non-small cell lung cancer (NSCLC) is a prominent etiology of cancer-related mortality. The heterogeneous nature of this disease impedes its accurate diagnosis and efficacious treatment. Consequently, constant advancements in research are imperative in order to comprehend its intricate nature. In addition to currently available therapies, the utilization of nanotechnology presents an opportunity to enhance the clinical outcomes of NSCLC patients. Notably, the burgeoning knowledge of the interaction between the immune system and cancer itself paves the way for developing novel, emerging immunotherapies for treating NSCLC in the early stages of the disease. It is believed that with the novel engineering avenues of nanomedicine, there is a possibility to overcome the inherent limitations derived from conventional and emerging treatments, such as off-site drug cytotoxicity, drug resistance, and administration methods. Combining nanotechnology with the convergence points of current therapies could open up new avenues for meeting the unmet needs of NSCLC treatment

MiR-34a Promotes Apoptosis and Inhibits Autophagy by Targeting HMGB1 in Acute Myeloid Leukemia Cells

Background: MiR-34a is identified as a tumor suppressor gene and involved in acute myeloid leukemia (AML) development. However, the regulatory mechanism of miR-34a in AML is unclear. Methods: The expression of miR-34a and HMGB1 in HL-60, THP-1 and HS-5 cells were detected by qRT-PCR and western blot. Lipofectamine 2000 was used to transfect with miR-34a mimics, miR-34a inhibitor, si-HMGB1, pcDNA 3.1-HMGB1, and corresponding controls. The apoptosis and autophagy of transfected AML cells were assessed by flow cytometry and western blot, respectively. Bioinformatics software and dual luciferase reporter assay were applied to predict and verify the target of miR-34a. The effects of miR-34a mimics or si-HMGB1 on chemotherapy-induced autophagy were further explored in HL-60 cells treated with all-trans retinoic acid (ATRA) along with lysosomal protease inhibitors E64d and pepstatin A. Results: MiR-34a was lower expressed and HMGB1 mRNA and proteins were both higher expressed in HL-60 and THP-1 cells compared with that in HS-5 cells. Higher expression levels of MiR-34 and lower expression levels of HMGB1 both significantly promoted apoptosis and inhibited autophagy in HL-60 and THP-1 cells. Dual luciferase reporter system confirmed that HMGB1 was a potential target of miR-34a. Moreover, overexpression of HMGB1 dramatically reversed the promotion of apoptosis and inhibition of autophagy mediated by higher expression level of miR-34a. Higher expression level of miR-34a and lower expression level of HMGB1 both inhibited chemotherapy-induced autophagy by stimulating the LC3 conversion. Conclusion: MiR-34a promoted cell apoptosis and inhibited autophagy by targeting HMGB1. Therefore, miR-34a may be a potential promising molecular target for AML therapy

No association between Id2 gene methylation and tetralogy of Fallot: a case-control study in China children

The aim of this case-control study was to investigate the correlation between the methylation levels of inhibitor of DNA binding 2 (Id2) gene and the incidence of tetralogy of Fallot (TOF) in children. The study included 31 TOF and 32 healthy control children. The methylation status of the Id2 gene was determined with time-of-flight mass spectrometry. Peripheral blood indices were detected, and their correlations with Id2 gene methylation were analyzed. Methylation analysis showed that there was no significant difference in the Id2 gene methylation level between the control and TOF groups (P > 0.05). After controlling the factors of gender, age, height and body weight, the analysis showed that there was no correlation between the methylation levels at each Id2 site and the red blood cells (RBC), hemoglobin (HGB) or hematocrit (HCT) (P > 0.05). However, the methylation levels at the CpG-16 and CpG-18.19 sites of the Id2 gene were negatively correlated with the mean corpuscular hemoglobin (MCH) (r = −0.337, P = 0.009; r = −0.392, P = 0.002) and mean corpuscular hemoglobin concentration (MCHC) (r = −0.363, P = 0.005; r = −0.286, P = 0.028), respectively. Our results suggest that the Id2 methylation might not be associated with the incidence of TOF. These results might contribute to the understanding of the etiology and mechanism of TOF in clinic

Privacy-Aware Online Task Offloading for Mobile-Edge Computing

Mobile edge computing (MEC) has been envisaged as one of the most promising technologies in the fifth generation (5G) mobile networks. It allows mobile devices to offload their computation-demanding and latency-critical tasks to the resource-rich MEC servers. Accordingly, MEC can significantly improve the latency performance and reduce energy consumption for mobile devices. Nonetheless, privacy leakage may occur during the task offloading process. Most existing works ignored these issues or just investigated the system-level solution for MEC. Privacy-aware and user-level task offloading optimization problems receive much less attention. In order to tackle these challenges, a privacy-preserving and device-managed task offloading scheme is proposed in this paper for MEC. This scheme can achieve near-optimal latency and energy performance while protecting the location privacy and usage pattern privacy of users. Firstly, we formulate the joint optimization problem of task offloading and privacy preservation as a semiparametric contextual multi-armed bandit (MAB) problem, which has a relaxed reward model. Then, we propose a privacy-aware online task offloading (PAOTO) algorithm based on the transformed Thompson sampling (TS) architecture, through which we can (1) receive the best possible delay and energy consumption performance, (2) achieve the goal of preserving privacy, and (3) obtain an online device-managed task offloading policy without requiring any system-level information. Simulation results demonstrate that the proposed scheme outperforms the existing methods in terms of minimizing the system cost and preserving the privacy of users