Improved Methods of Sepsis Case Identification and the Effects of Treatment with Low Dose Steroids: A Dissertation

Sepsis is the leading cause of death among critically ill patients and the 10th most common cause of death overall in the United States. The mortality rates increase with severity of the disease, ranging from 15% for sepsis to 60% for septic shock. Patient with sepsis can present varied clinical symptoms depending on the personal predisposition, causal microorganism, organ system involved, and disease severity. To facilitate sepsis diagnosis, the first sepsis consensus definitions was published in 1991 and then updated in 2001. Early recognition of a sepsis patient followed with timely and appropriate treatment and management strategies have been shown to significantly reduce sepsis-related mortality, and allows care to be provided at lower costs. Despite the rapid progress in the knowledge of pathophysiological mechanisms of sepsis and its treatment in the last two decades, identifying patient with sepsis and therapeutic approaches to sepsis and its complications remains challenging to critical care clinicians. Hence, the objectives of this thesis were to 1) evaluate the test characteristics of the two sepsis consensus definitions and delineate the differences in patient profile among patients meeting or not meeting sepsis definitions; 2) determine the relationship between the changes in several physiological parameters before sepsis onset and sepsis, and to determine whether these parameters could be used to identify sepsis in critically ill adults; 3) evaluate the effect of corticosteroids therapy on patient mortality. Data used in this thesis were prospectively collected from an electronic medical record system for all the adult patients admitted into the seven critical care units (ICUs) in a tertiary medical center. Besides analyzing data at the ICU stay level, we investigated patient information in various time frames, including 24-hour, 12-hour, and 6-hour time windows. In the first study of this thesis, the 1991 sepsis definition was found to have a high sensitivity of 94.6%, but a low specificity of 61.0%. The 2001 sepsis definition had a slightly increased sensitivity but a decreased specificity, which was 96.9% and 58.3%, respectively. The areas under the ROC curve for the two consensus definitions were similar, but less than optimal. The sensitivity and area under the ROC curve of both definitions were lower at the 24-hour time window level than those of the unit stay level, though the specificity increased slightly. At the time window level, the 1991 definitions performed slightly better than the 2001 definition. In the second study, minimum systolic blood pressure performed the best, followed by maximum respiratory rate in discriminating sepsis patients from SIRS patients. Maximum heart rate and maximum respiratory rate can differentiate sepsis patients from non-SIRS patients fairly well. The area under ROC of the combination of five physiological parameters was 0.74 and 0.90 for comparing sepsis to non-infectious SIRS patients and comparing sepsis to non-SIRS patients, respectively. Parameters typically performed better in 24-hour windows compared to 6-hour or 12-hour windows. In the third study, significantly increased hospital mortality and ICU mortality were observed in the group treated with low-dose corticosteroids than the control group based on the propensity score matched comparisons, and multivariate logistic regression analyses after adjustment for propensity score alone, covariates, or propensity score (in deciles) and covariates. This thesis advances the existing knowledge by systemically evaluating the test characteristics for the 1991 and 2001 sepsis consensus definitions, delineating physiological signs and symptoms of deterioration in the preceding 24 hours prior to sepsis onset, assessing the prediction performances of single or combined physiological parameters, and examining the use of corticosteroids treatment and survival among septic shock patients. In addition, this thesis sets an innovative example on how to use data from electronic medical records as these surveillance systems are becoming increasingly popular. The results of these studies suggest that a more parsimonious set of definitional criteria for sepsis diagnosis are needed to improve sepsis case identification. In addition, continuously monitored physiological parameters could help to identify patients who show signs of deterioration prior to developing sepsis. Last but not least, caution should be used when considering a recommendation on the use of low dose corticosteroids in clinical practice guidelines for the management of sepsis

Expression and clinical significance of RHCG in endometrial cancer

Endometrial cancer (EC) is the most common gynecological cancer. Rhesus family, C glycoprotein (RHCG) has been evidenced to be involved in the occurrence and development of various tumors. This study aimed to investigate the expression and clinical significance of RHCG in EC. Bioinformatics analysis was based on the RNAseq counts data from TCGA database, and the prognosis analysis was performed using the Kaplan-Meier method; 4 cases of endometrioid adenocarcinomas samples and 4 cases of normal proliferative endometrium were collected for qPCR and western blot; immunohistochemistry analysis was employed to assess the expression of RHCG in a tissue microarray; the correlation between RHCG and clinicopathological factors was analyzed through Mann-Whitney U test. The lentiviral interference vector was further constructed. The results demonstrated that RHCG was highly expressed in EC tissues, and RHCG was an independent factor affecting the overall survival of patients. Additionally, the expression of RHCG was related to FIGO stage and tumor infiltrate. After interfering with shRHCG, the proliferation activity of EC cells decreased, the migration ability of cells decreased, the apoptosis of cells increased, and the tumor outgrowth was arrested. In summary, RHCG promotes the malignant proliferation and migration of EC, and makes the cells have anti-apoptotic activity. Our study provides a theoretical basis for RHCG to become a potential therapeutic target for EC in the futur

Effect of irrigation frequency during the growing season of winter wheat on the water use efficiency of summer maize in a double cropping system

Our aim was to investigate the potential effects of irrigation frequency during the growing season of winter wheat on the water use efficiency (WUE) of summer maize in a double cropping system. To this end, we conducted a field experiment with winter wheat cultivated with 1, 2, and 3 irrigation applications with 120 mm water at the time of stem elongation, heading, or milking. The results showed that later irrigation applications increased soil moisture before sowing (SMBS) of summer maize. Summer maize grain yield was enhanced in both the common and excessively rainy years with increased SMBS; however, irrigation during the later growing season of winter wheat in rainy years could increase deep percolation of summer maize. In common and rainy years, the more the SMBS, the higher was the grain yield of summer maize. The highest WUE for summer maize was obtained when it was grown after winter wheat irrigated with 120 mm water at milking or 60 mm water at each, the stem elongation and heading stages. Considering the combined WUE of winter wheat and summer maize, the authors think that winter wheat should be irrigated at the stem elongation and heading stages to achieve reasonable WUE and grain yield for both crops

Current Status and Potential Challenges of Cell-Based Therapy for Treating Status Epilepticus and Chronic Epilepsy

Epilepsy is the fourth most common neurological condition characterized by recurrent unprovoked seizures. Chronic and recurrent seizures may give rise to cell necrosis, astrocyte activation, neuron death, reactive oxygen species (ROS) production, and mitochondria dysfunction. Recent studies have shown that cell-based therapy is a promising treatment option for epilepsy. Various stem cell types were used for treatment of epilepsy in basic and experimental researches. It is especially vital to gauge the efficacy of distinct donor cell types, such as the embryonic stem cells and induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), hippocampal precursor cells, γ-aminobutyric acid-ergic progenitors, neural stem cells. The goal of this chapter is to evaluate the progress made hitherto in this area and to discuss the prospect for cell-based therapy for epilepsy

Theoretical and Experimental Research on The Optimal Displacement Ratio of Rotary Two-Stage Inverter Compressor With Vapor Injection

Displacement ratio is one of the most important parameters of designing rotary two-stage inverter compressor with vapor injection, which decides the COP (Coefficient of Performance) of the compressor. The optimal displacement ratio can bring about the highest COP. The mathematical model of the optimal displacement ratio of rotary two-stage inverter compressor with vapor injection has been developed and verified with the test data. It can be seen from theoretical and experimental research that the optimal displacement ratio of compressors in different working conditions can be obtained accurately by the mathematical model introduced in this paper

Jing Tong Yu Shu, a traditional Chinese medicine, suppresses IL-1β and IL-6 gene expressions in macrophages, and alleviates endometriosis

Purpose: To evaluate the effect of a traditional Chinese medicine, Jing Tong Yu Shu (JTYS) on endometriosis in a rat surgical model. Methods: Endometriosis was induced in 40 female rats. The rats were randomly divided into 4 groups: three JTYS groups given different doses of the drug, and a saline group. After four weeks of treatment with JTYS, the volume of the endometriotic explants was measured, and the levels of IL-1β and IL-6 in peritoneal fluid and serum were determined by enzyme-linked immunosorbent assay (ELISA). The production of cytokine IL-1β and IL-6 by peritoneal macrophages was also measured for each group. Results: JTYS treatment brought about regression of implants and inhibition of IL-1β and IL-6 production in a dose-dependent manner, with high-dose JTYS eliciting 66.76 % reduction in mean endometriotic explant volume. Plasma and peritoneal fluid levels of IL-1β and IL-6 were significantly lower in the high-dose JTYS group than in the saline group (p < 0.05). However, JTYS treatment significantly inhibited IL-1β and IL-6 production in peritoneal macrophages (p < 0.05). Conclusion: These results suggest that JTYS treatment leads to regression of endometriotic lesions in rat. Thus, JTYS has the potential to be developed into a new drug for the treatment of endometriosis. Keywords: Endometriosis, Interleukins, Traditional Chinese medicine, Jing Tong Yu Shu Macrophage

m6A reader proteins: the executive factors in modulating viral replication and host immune response

N6-Methyladenosine (m6A) modification is the most abundant covalent modification of RNA. It is a reversible and dynamic process induced by various cellular stresses including viral infection. Many m6A methylations have been discovered, including on the genome of RNA viruses and on RNA transcripts of DNA viruses, and these methylations play a positive or negative role on the viral life cycle depending on the viral species. The m6A machinery, including the writer, eraser, and reader proteins, achieves its gene regulatory role by functioning in an orchestrated manner. Notably, data suggest that the biological effects of m6A on target mRNAs predominantly depend on the recognition and binding of different m6A readers. These readers include, but are not limited to, the YT521-B homology (YTH) domain family, heterogeneous nuclear ribonucleoproteins (HNRNPs), insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs), and many others discovered recently. Indeed, m6A readers have been recognized not only as regulators of RNA metabolism but also as participants in a variety of biological processes, although some of these reported roles are still controversial. Here, we will summarize the recent advances in the discovery, classification, and functional characterization of m6A reader proteins, particularly focusing on their roles and mechanisms of action in RNA metabolism, gene expression, and viral replication. In addition, we also briefly discuss the m6A-associated host immune responses in viral infection