Loss of Hepatic Angiotensinogen Attenuates Sepsis-Induced Myocardial Dysfunction.

[Figure: see text].

Therapeutic approaches targeting renin-angiotensin system in sepsis and its complications.

Sepsis, caused by the inappropriate host response to infection, is characterized by excessive inflammatory response and organ dysfunction, thus becomes a critical clinical problem. Commonly, sepsis may progress to septic shock and severe complications, including acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), sepsis-induced myocardial dysfunction (SIMD), liver dysfunction, cerebral dysfunction, and skeletal muscle atrophy, which predominantly contribute to high mortality. Additionally, the global pandemic of coronavirus disease 2019 (COVID-19) raised the concern of development of effectve therapeutic strategies for viral sepsis. Renin-angiotensin system (RAS) may represent as a potent therapeutic target for sepsis therapy. The emerging role of RAS in the pathogenesis of sepsis has been investigated and several preclinical and clinical trials targeting RAS for sepsis treatment revealed promising outcomes. Herein, we attempt to review the effects and mechanisms of RAS manipulation on sepsis and its complications and provide new insights into optimizing RAS interventions for sepsis treatment.

Prognostic value of hypothyroidism in patients undergoing intensity-modulated radiation therapy for nasopharyngeal carcinoma.

BACKGROUND: The purpose of this study was to investigate the effect of hypothyroidism and thyroxine replacement therapy on the prognosis of nasopharyngeal carcinoma (NPC) patients. METHODS: The clinical data of 284 NPC patients, who received intensity-modulated radiation therapy (IMRT) between January 2011 and December 2016, were retrospectively analyzed. RESULTS: Hypothyroidism occurred in 38% of patients. Patients with hypothyroidism had significantly better disease-free survival (DFS) (p = 0.002) and relapse-free survival (RFS) (p = 0.008). Multivariate analysis showed that hypothyroidism was a positive independent prognostic factor (DFS and RFS). Among the patients with hypothyroidism, thyroxine replacement therapy did not yield inferior survival (DFS, RFS, all p > 0.05). CONCLUSIONS: The NPC patients with complete response are at risk of hypothyroidism, which is attributable to escalating dose. These patients experienced clinical hypothyroidism could be adequately treated with thyroid hormone replacement. Further investigation of the underlying biological mechanism and potential therapeutic implications are required.

EBV-microRNAs as Potential Biomarkers in EBV-Related Fever: A Narrative Review.

At present, timely and accurate diagnosis and effective treatment of Epstein-Barr Virus (EBV) infection-associated fever remain a difficult challenge. EBV encodes 44 mature microRNAs (miRNAs) that inhibit viral lysis, adjust inflammatory response, regulate cellular apoptosis, promote tumor genesis and metastasis, and regulate tumor cell metabolism. Herein, we have collected the specific expression data of EBV-miRNAs in EBV-related fevers [including infectious mononucleosis (IM), EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), chronic active EBV infection (CAEBV), and EBV-related tumors] and proposed the potential value of EBV-miRNAs as biomarkers to assist in the identification, diagnosis, and prognosis of EBV-related fever, as well as therapeutic targets for drug development.

Network Analysis Reveals TNF as a Major Hub of Reactive Inflammation Following Spinal Cord Injury.

Spinal cord injury (SCI) leads to reactive inflammation and other harmful events that limit spinal cord regeneration. We propose an approach for studying the mechanisms at the levels of network topology, gene ontology, signaling pathways, and disease inference. We treated inflammatory mediators as toxic chemicals and retrieved the genes and interacting proteins associated with them via a set of biological medical databases and software. We identified >10,000 genes associated with SCI. Tumor necrosis factor (TNF) had the highest scores, and the top 30 were adopted as core data. In the core interacting protein network, TNF and other top 10 nodes were the major hubs. The core members were involved in cellular responses and metabolic processes, as components of the extracellular space and regions, in protein-binding and receptor-binding functions, as well as in the TNF signaling pathway. In addition, both seizures and SCI were highly associated with TNF levels; therefore, for achieving a better curative effect on SCI, TNF and other major hubs should be targeted together according to the theory of network intervention, rather than a single target such as TNF alone. Furthermore, certain drugs used to treat epilepsy could be used to treat SCI as adjuvants.

Numerical characterization of regenerative axons growing along a spherical multifunctional scaffold after spinal cord injury.

Spinal cord injury (SCI) followed by extensive cell loss, inflammation, and scarring, often permanently damages neurological function. Biomaterial scaffolds are promising but currently have limited applicability in SCI because after entering the scaffold, regenerating axons tend to become trapped and rarelyre-enter the host tissue, the reasons for which remain to be completely explored. Here, we propose a mathematical model and computer simulation for characterizing regenerative axons growing along a scaffold following SCI, and how their growth may be guided. The model assumed a solid, spherical, multifunctional, biomaterial scaffold, that would bridge the rostral and caudal stumps of a completely transected spinal cord in a rat model and would guide the rostral regenerative axons toward the caudal tissue. Other assumptions include the whole scaffold being coated with extracellular matrix components, and the caudal area being additionally seeded with chemoattractants. The chemical factors on and around the scaffold were formulated to several coupled variables, and the parameter values were derived fromexisting experimental data. Special attention was given to the effects of coating strength, seeding location, and seeding density, as well as the ramp slope of the scaffold, on axonal regeneration. In numerical simulations, a slimmer scaffold provided a small slope at the entry "on-ramp" area that improved the success rate of axonal regeneration. If success rates are high, an increased number of regenerative axons traverse through the narrow channels, causing congestion and lowering the growth rate. An increase in the number of severed axons (300-12000) did not significantly affect the growth rate, but it reduced the success rate of axonal regeneration. However, an increase in the seeding densities of the complexes on the whole scaffold, and that in the seeding densities of the chemoattractants on the caudal area, improved both the success and growth rates. However, an increase in the density of thecomplexes on the whole scaffold risks an over-eutrophic surface that harms axonal regeneration.Although theoretical predictions are yet to be validated directly by experiments, this theoretical tool can advance the treatment of SCI, and is also applicable to scaffolds with other architectures.

Estimation of the occupational exposure dose for medical diagnostic X-ray workers in Jiangsu, China, using a retrospective dosimetry method.

Medical diagnostic X-ray workers are one occupational group that has exposure to continuous low doses of external radiation over their working lifetimes. Current ICRP recommendations [ICRP. Recommendations of the International Commission on Radiological Protection. ICRP Publication 60. Ann ICRP 1991;21 (1-3)] state that there is no threshold of stochastic effects induced by radiation exposure such as carcinogenicity or genetic defects, and that the frequency of the effects is proportional to the amount of exposure to low levels of radiation, which is measured by radiation dose. In order to determine the dose information for this special occupational group over their working lifetimes (focusing particularly on workers exposed before 1985, when there was no personal dose monitoring), a sampling survey of the occupational history for these workers was conducted and an occupational history database was established. Using the database and retrospective dosimetry method of Zhang et al. (A retrospective dosimetry method for occupational dose for Chinese medical diagnostic X-ray workers. Radiat Prot Dosimetry 1998;77:69-72), the annual occupational exposure dose for medical diagnostic X-ray personnel working between 1950 and 2011 was computerized. Some annual dose results estimated using the proposed method were numerically in good agreement with the monitoring results. The average of the annual dose for these medical workers peaked during the mid-1950s and then declined, reaching very low levels by the 1990s and remaining at those levels thereafter. The trend in the annual dose is similar to that reported by earlier studies by Zielinski et al. (Health outcomes of low-dose ionizing radiation exposure among medical workers: a cohort study of the Canadian national dose registry of radiation workers. Int J Occup Med Environ Health 2009;22:149-56). The dose calculated by the retrospective dosimetry method can truly indicate the degree of the workers' exposure in their medical X-ray diagnostic work.

Nested Case-control Study of Occupational Radiation Exposure and Breast and Esophagus Cancer Risk among Medical Diagnostic X Ray Workers in Jiangsu of China.

Medical diagnostic X-ray workers are one occupational group that expose to the long-term low-dose external radiation over their working lifetime, and they may under risk of different cancers. This study aims to determine the relationship between the occupational X-ray radiation exposure and cancer risk among these workers in Jiangsu, China. We conducted Nested case-control study to investigate the occupational X-ray radiation exposure and cancer risk. Data were collected through self-administered questionnaire, which includes but not limits to demographic data, personal behaviors and family history of cancer. Retrospective dose reconstruction was conducted to estimate the cumulative doses of the x-ray workers. Inferential statistics, t-test and 2 tests were used to compare the differences between each group. We used the logistic regression model to calculate the odds ratio (OR) and 95% confidence interval (CI) of cancer by adjusting the age, gender. All 34 breast cancer cases and 45 esophageal cancer cases that detected in a cohort conducted among health workers between 1950~2011 were included in this presented study, and 158 cancer-free controls were selected by frequency-matched (1:2). Our study found that the occupational radiation exposure was associated with a significantly increased cancer risk compared with the control, especially in breast cancer and esophageal cancer (adjusted OR=2.90, 95% CI: 1.19-7.04 for breast cancer; OR=4.19, 95% CI: 1.87-9.38 for esophageal cancer, and OR=3.43, 95% CI: 1.92-6.12 for total cancer, respectively). The occupational X-ray radiation exposure was associated with increasing cancer risk, which indicates that proper intervention and prevention strategies may be needed in order to bring down the occupational cancer risk.