Unveiling an Asymptomatic Cardiac Air-Gunshot Injury.

Interventricular septum pellet retention after air-gunshot injury in a persistently asymptomatic patient is a rare, clinically significant occurrence. Management involved monitoring, echocardiography, and computed tomography scans. After risk-benefit analysis, we favored a nonsurgical management without prophylactic antibiotics or colchicine. No post-traumatic pericarditis was observed. Patient remained asymptomatic and in excellent condition at 1-month follow-up.

Practical Solutions for Healthcare Worker Protection During the COVID-19 Pandemic Response in the Ambulatory, Emergency, and Inpatient Settings.

OBJECTIVE: Protecting healthcare workers is an essential component of a successful response to the COVID-19 pandemic. The resource intensive nature of infectious disease protection, budgetary constraints, and global shortages of personal protective equipment (PPE) make this a daunting task. Practical, easily implemented strategies for healthcare workers (HCW) protection are needed. METHODS: We cross-reference the "Systems, Space, Staff, and Stuff" paradigm from disaster management and the "Hierarchy of Controls" approach to infection prevention from the Center for Disease Control and Prevention (CDC) to generate a narrative overview of worker protection strategies relevant to COVID-19. RESULTS: Alternative types of PPE, management of hazards, and reorganizing how people work can optimize HCWs protection. CONCLUSIONS: A comprehensive PPE strategy can utilize the "systems, space, staff, stuff" paradigm of disaster management to identify new or underutilized solutions to HCWs protection.

The forensic pathological analysis of sport-related sudden cardiac death in Southern China.

Studies regarding sport-related sudden cardiac death (SCD) mainly focus on competitive athletes; similar data are rare in the general population, especially in China. We conducted a retrospective study (from September 1998 to August 2013) to investigate the aetiological distribution and epidemiological features of sport-related SCD in Southern China. Selections of cases are based on details, and two subgroups were established: one was the sport-related SCD group, and the other was the disease-free accident victims group which was matched with the sport-related SCD group in gender, age and year of death. Among the 3770 sudden-death cases, 1656 cases were SCD cases. A total of 65 cases (57 males) out of 1 656 SCD cases were sport-related. The age range of the 65 sport-related SCD cases was from 12 to 68 years old with a mean (35.92 ± 14.23) years old. Only two of these cases were competitive athletes. The most common circumstances of the 65 sport-related SCD cases were heavy physical labour (46.15%) and running (30.77%). The three leading forensic diagnoses were the coronary atherosclerotic disease (CAD, 28 cases), cardiomyopathy (CM, 14 cases) and sudden unexplained death (7 cases). CM was the most common forensic diagnosis in those ≤35 years old, while CAD was the most common one in those >35 years old. Left anterior descending in which atherosclerotic plaques was most commonly found was the principal artery branch associated with sport-related SCD. There was a statistically significant difference in the weight of hearts between the 65 sport-related SCD cases and 65 diseases-free accidental cases. This study highlights the need to attract public attention to sport-related SCD and to issue a prevention strategy to the public, and to make the SCD-related genetic sequencing a routine tool in both forensic pathological examination and clinic screening.

A Nestin-Cyclin-Dependent Kinase 5-Dynamin-Related Protein 1 Axis Regulates Neural Stem/Progenitor Cell Stemness via a Metabolic Shift.

Neural stem/progenitor cells (NSPCs) transplantation provides an alternative approach for various central nervous system (CNS) diseases treatment, while the difficulties in NSPC acquisition and expansion limit their further application. Unveiling the mechanism of NSPC stemness regulation may contribute to its further application. Nestin, generally recognized as a marker of NSPCs, plays a crucial role in the CNS development and NSPC stemness maintenance. Here, we report that Nestin loss triggers mitochondrial network remodeling and enhances oxidative phosphorylation (OXPHOS) in NSPCs treated with Nestin RNA interference (RNAi). Mitochondrial morphology is dynamically controlled by the balance between fission and fusion mediators; one of these mediators, the pro-fission factor, dynamin-related protein 1 (Drp1), shows decreased activation in Nestin-knockdown cells. Upstream, Drp1 phosphorylation is under control of the cytosolic cyclin-dependent kinase 5 (Cdk5). Inhibition of Cdk5 using RNAi or a chemical inhibitor (roscovitine) induces mitochondrial elongation and promotes mitochondrial respiration, indicating that Cdk5-dependent Drp1 phosphorylation participates in mitochondrial metabolism and NSPC stemness regulation. Strikingly, Nestin knockdown results in Cdk5 redistribution, with less remaining in the cytosol, leading to mitochondrial remodeling. We identify Nestin1-640 sequesters Cdk5 in the cytosol and phosphorylates Drp1 subsequently. Together, our results show that a Nestin-Cdk5-Drp1 axis negatively regulates mitochondrial OXPHOS, which is indispensable for the maintenance of NSPC stemness. Stem Cells 2018;36:589-601.

A novel role of cellular interactions in vascular calcification.

A series of clinical trials have confirmed the correlation between vascular calcification (VC) and cardiovascular events and mortality. However, current treatments have little effects on the regression of VC. Potent and illustrative mechanisms have been proven to exist in both bone metabolism and VC, indicating that these two processes share similarities in onset and progression. Multiple osteoblast-like cells and signaling pathways are involved in the process of VC. In this review, we summarized the roles of different osteoblast-like cells and we emphasized on how they communicated and interacted with each other using different signaling pathways. Further studies are needed to uncover the underlying mechanisms and to provide novel therapies for VC.

Secreted phospholipase A2 of Clonorchis sinensis activates hepatic stellate cells through a pathway involving JNK signalling.

BACKGROUND: Secreted phospholipase A2 (sPLA2) is a protein secreted by Clonorchis sinensis and is a component of excretory and secretory products (CsESPs). Phospholipase A2 is well known for its role in liver fibrosis and inhibition of tumour cells. The JNK signalling pathway is involved in hepatic stellate cells (HSCs) activation. Blocking JNK activity with SP600125 inhibits HSCs activation. In a previous study, the protein CssPLA2 was expressed in insoluble inclusion bodies. Therefore, it's necessary to express CssPLA2 in water-soluble form and determine whether the enzymatic activity of CssPLA2 or cell signalling pathways is involved in liver fibrosis caused by clonorchiasis. METHODS: Balb/C mice were given an abdominal injection of MBP-CssPLA2. Liver sections with HE and Masson staining were observed to detect accumulation of collagen. Western blot of mouse liver was done to detect the activation of JNK signalling pathway. In vitro, HSCs were incubated with MBP-CssPLA2 to detect the activation of HSCs as well as the activation of JNK signalling pathway. The mutant of MBP-CssPLA2 without enzymatic activity was constructed and was also incubated with HSCs to check whether activation of the HSCs was related to the enzymatic activity of MBP-CssPLA2. RESULTS: The recombinant protein MBP-CssPLA2 was expressed soluble and of good enzymatic activity. A mutant of CssPLA2, without enzymatic activity, was also constructed. In vivo liver sections of Balb/C mice that were given an abdominal injection of 50 µg/ml MBP-CssPLA2 showed an obvious accumulation of collagen and a clear band of P-JNK1 could be seen by western blot of the liver tissue. In vitro, MBP-CssPLA2, as well as the mutant, was incubated with HSCs and it was proved that activation of HSCs was related to activation of the JNK signalling pathway instead of the enzymatic activity of MBP-CssPLA2. CONCLUSIONS: Activation of HSCs by CssPLA2 is related to the activation of the JNK signalling pathway instead of the enzymatic activity of CssPLA2. This finding could provide a promising treatment strategy to interrupt the process of liver fibrosis caused by clonorchiasis.

The Diagnostic Value of Quantitative Assessment of Diatom Test for Drowning: An Analysis of 128 Water-related Death Cases using Microwave Digestion-Vacuum Filtration-Automated Scanning Electron Microscopy.

The value of diatom test for the diagnosis of drowning remains controversial. The conventional forensic diatom test with low sensitivity is not a useful tool to provide accurate information about diatom in the tissues and organs. To improve the sensitivity of the diatom test, we developed a novel method called the Microwave Digestion-Vacuum Filtration-Automated Scanning Electron Microscopy (MD-VF-Auto SEM) method which resulted in a high recovery of diatoms. In this article, we analyzed 128 water-related death cases. Our results showed that the MD-VF-Auto SEM method could achieve a much higher positive rate (0.97) in drowning cases. Large amounts of diatoms are retained, even concentrated, in the lung tissues during the intense breathing movement in drowning process. This might be useful for the diagnosis of drowning. Our research indicates that the MD-VF-Auto SEM method would be a valuable methodology in the study of diatom test for the forensic community.

Brugada syndrome: a fatal disease with complex genetic etiologies - still a long way to go.

Brugada syndrome (BrS) is an arrhythmogenic disorder which was first described in 1992. This disease is a channelopathy characterized by ST-segment elevations in the right precordial leads and is susceptible to sudden death. BrS is a fatal disease with gender and age preferences. It occurs mainly in young male subjects with a structurally normal heart and silently progresses to sudden death with no significant symptoms. The prevalence of BrS has been reported in the ranges of 5-20 per 10 000 people. The disease is more prevalent in Asia. Nowadays, numerous variations in 23 genes have been linked to BrS since the first gene SCN5A has been associated with BrS in 1998. Not only can clinical specialists apply these discoveries in risk assessment, diagnosis and personal medicine, but also forensic pathologists can make full use of these variations to conduct death cause identification. However, despite the progress in genetics, these associated genes can only account for approximately 35% of the BrS cases while the etiology of the remaining BrS cases is still unexplained. In this review, we discussed the prevalence, the genes associated with BrS and the application of molecular autopsy in forensic pathology. We also summarized the present obstacles, and provided a new insight into the genetic basis of BrS.

Vessel heterogeneity of TIMI frame count and its relation to P-wave dispersion in patients with coronary slow flow.

BACKGROUND: The vessel heterogeneity of thrombolysis in myocardial infarction (TIMI) frame count (TFC) in patients with coronary slow flow (CSF) remains to be further evaluated, and the correlation between TFC heterogeneity and P-wave dispersion (PWD) has not been elucidated. We aim to investigate the vessel heterogeneity of TFC in coronary arteries, and its relation to PWD in patients with CSF and otherwise normal coronary arteries. METHODS: We studied 72 patients with angiographically documented CSF and 66 age- and gender-matched control subjects. The coefficient of variation (CV) and mean TFC of the three vessels were calculated. P-wave duration and PWD were measured on the standard electrocardiograms (ECGs). RESULTS: The mean TFC and CV were both significantly higher in CSF patients than in controls (P<0.001 for both comparisons). The maximum P-wave duration (Pmax) and PWD were found to be significantly higher in CSF patients than in controls (P<0.001 for both comparisons). In patients with CSF, both Pmax and PWD were mildly correlated to mean TFC (r=0.318, P=0.009; and r=0.307, P=0.010), and were more significantly correlated to CV (r=0.506, P<0.001; and r=0.579, P<0.001). CONCLUSIONS: These data demonstrate that variability of TFC in three coronary arteries is increased in CSF patients, and that the vessel heterogeneity in coronary flow might be intimately associated with PWD.

Low Response of Renin-Angiotensin System to Sodium Intake Intervention in Chinese Hypertensive Patients.

The interactions of sodium balance and response of renin-angiotensin-aldosterone system are important for maintaining the hemodynamic stability in physiological conditions. However, the influence of short-term sodium intake intervention in the response of renin-angiotensin system (RAS) on hypertensive patients is still unclear. Thus, we conducted a clinical trial to investigate the effects of short-term sodium intake intervention on the response of RAS in hypertensive patients.One hundred twenty-five primary Chinese hypertensive patients were divided into high, moderate, and low sodium groups by 24-hour urinary sodium excretion (UNa). All the patients received a 10-day dietary sodium intake intervention with standardized sodium (173.91mmol/day) and potassium (61.53mmol/day). Blood pressure, urinary sodium, urinary potassium, plasma sodium, potassium, creatinine, the levels of plasma renin activity, plasma angiotensin II concentrations (AT-II), and plasma aldosterone concentrations were detected before and after the intervention.Before the intervention, no differences were found in blood pressure and RAS among 3 groups. After standardized dietary sodium intake intervention, both UNa excretion and systolic pressure decreased in high-sodium group, while they increased in moderate and low-sodium groups. Intriguingly, there were no changes in the levels of plasma renin activity, AT-II, and plasma aldosterone concentrations among 3 groups during the intervention.The present study demonstrated that the influenced sodium excretion and blood pressure by short-term sodium intake intervention were independent of RAS quick response in Chinese hypertensive patients.

Bone marrow-derived mesenchymal stem cell-secreted IL-8 promotes the angiogenesis and growth of colorectal cancer.

Mesenchymal stem cells (MSCs) have recently been shown to home to tumors and contribute to the formation of the tumor-associated stroma. In addition, MSCs can secrete paracrine factors to facilitate tumor progression. However, the involvement of MSC-derived cytokines in colorectal cancer (CRC) angiogenesis and growth has not been clearly addressed. In this study, we report that interleukin-8 (IL-8) was the most highly upregulated pro-angiogenic factor in MSCs co-cultured with CRC cells and was expressed at substantially higher levels in MSCs than CRC cells. To evaluate the effect of MSC-derived IL-8 on CRC angiogenesis and growth, we used MSCs that expressed small hairpin (interfering) RNAs (shRNA) targeting IL-8 (shIL-8-MSCs). We found that MSC-secreted IL-8 promoted human umbilical vein endothelial cell (HUVEC) proliferation and migration, tube-formation ability and CRC cell proliferation. Additionally, in vivo studies showed that MSCs promoted tumor angiogenesis partially through IL-8. Taken together, these findings suggest that IL-8 secreted by MSCs promotes CRC angiogenesis and growth and can therefore serve as a potential novel therapeutic target.

Pigment epithelium-derived factor (PEDF) inhibits breast cancer metastasis by down-regulating fibronectin.

Pigment epithelium-derived factor (PEDF) plays an important role in the tumor growth and metastasis inhibition. It has been reported that PEDF expression is significantly reduced in breast cancer, and associated with disease progression and poor patient outcome. However, the exact mechanism of PEDF on breast cancer metastasis including liver and lung metastasis remains unclear. The present study aims to reveal the impact of PEDF on breast cancer. The orthotopic tumor mice model inoculated by MDA-MB-231 cells stably expressing PEDF or control cells was used to assess liver and lung metastasis of breast cancer. In vitro, migration and invasion experiments were used to detect the metastatic abilities of MDA-MB-231 and SKBR3 breast cancer cells with or without overexpression of PEDF. The metastatic-related molecules including EMT makers, fibronectin, and p-AKT and p-ERK were detected by qRT-PCR, Western blot, and Fluorescent immunocytochemistry. PEDF significantly inhibited breast cancer growth and metastasis in vivo and in vitro. Mechanically, PEDF inhibited breast cancer cell migration and invasion by down-regulating fibronectin and subsequent MMP2/MMP9 reduction via p-ERK and p-AKT signaling pathways. However, PEDF had no effect on EMT conversion in the breast cancer cells which was usually involved in cancer metastasis. Furthermore, the study showed that laminin receptor mediated the down-regulation of fibronectin by PEDF. These results reported for the first time that PEDF inhibited breast cancer metastasis by down-regulating fibronectin via laminin receptor/AKT/ERK pathway. Our findings demonstrated PEDF as a dual effector in limiting breast cancer growth and metastasis and highlighted a new avenue to block breast cancer progression.