[Relationship between D-dimer concentration and inflammatory factors or organ function in patients with coronavirus disease 2019].

OBJECTIVE: To explore the relationship between D-dimer concentration and inflammatory factors or organ function in patients with coronavirus disease 2019 (COVID-19). METHODS: A retrospective study was conducted. The clinical data of 72 patients with COVID-19 admitted to intensive unit of Tongji Guanggu Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in Wuhan, Hubei Province from February 10th to 29th in 2020 were collected, including their general information, routine blood test, coagulation function, inflammatory parameters, cytokines, and organ function related laboratory parameters at admission. The patients were divided into two groups, namely D-dimer normal group (< 0.5 mg/L) and D-dimer elevated group (≥ 0.5 mg/L). The differences of general data, inflammatory parameters and cytokines between the two groups were compared. Besides, the correlation between D-dimer and organ function was analyzed by linear regression. The change in sequential organ failure assessment (SOFA) between the first visit after the onset of the disease and admission to intensive unit ≥ 2 was defined as being combined with organ damage. Receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of D-dimer on organ damage in patients with COVID-19. RESULTS: 65.3% of the 72 patients had abnormal coagulation. The D-dimer level of COVID-19 patients gradually increased with the aggravation of the disease, and the levels of ordinary type (n = 14), severe type (n = 49), and critical type (n = 9) were 0.43 (0.22, 0.89), 0.66 (0.26, 1.36), and 2.65 (0.68, 15.45) mg/L, respectively, with statistically significant difference (P < 0.05). Thirty-two patients (44.4%) had normal D-dimer, and 40 (55.6%) had elevated D-dimer. Compared with the normal D-dimer group, the patients in the D-dimer elevated group were older (years old: 67.7±11.6 vs. 54.0±13.1), and the levels of white blood cell count (WBC), neutrophil count (NEU), procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), interleukins (IL-6, IL-8, IL-10), IL-2 receptor (IL-2R) and tumor necrosis factor-α (TNF-α) at admission were significantly higher [WBC (×109/L): 7.16 (5.55, 9.75) vs. 5.25 (4.59, 6.98), NEU (×109/L): 7.11±5.46 vs. 3.33±1.58, PCT (µg/L): 0.08 (0.06, 0.21) vs. 0.05 (0.04, 0.06), hs-CRP (mg/L): 27.9 (3.4, 58.8) vs. 1.3 (0.8, 6.6), IL-6 (ng/L): 11.80 (2.97, 30.61) vs. 1.98 (1.50, 4.73), IL-8 (ng/L): 19.90 (13.33, 42.28) vs. 9.40 (12.35, 15.30), IL-10 (ng/L): 5.00 (5.00, 8.38) vs. 5.00 (5.00, 5.00), IL-2R (kU/L): 907.90±458.42 vs. 572.13±274.55, TNF-α (ng/L): 10.94±5.95 vs. 7.77±3.67], while lymphocyte (LYM) and monocyte (MON) counts were lower [LYM (×109/L): 1.14±0.49 vs. 1.46±0.42, MON (×109/L): 0.63±0.25 vs. 0.87±0.21], with significant differences (all P < 0.05). Linear regression analysis showed that D-dimer level was negatively related with pulse oxygen saturation (SpO2), oxygenation index (PaO2/FiO2) and platelet count (PLT) with ß values of -0.493, -11.615, and -0.018, respectively (all P < 0.05). However, D-dimer level was positively related with respiratory rate (RR), aspartate aminotransferase (AST), total bilirubin (TBil) and direct bilirubin (DBil) with ß values of 0.485, 0.107, 0.291, and 0.404 (all P < 0.05). ROC curve analysis showed that the area under ROC curve (AUC) of D-dimer for predicting organ injury in COVID-19 patients was 0.889, and the 95% confidence interval (95%CI) was 0.753-1.000. When the optimal cut-off value was 2.36 mg/L, the sensitivity was 85.7%, and the specificity was 78.1%. CONCLUSIONS: D-dimer levels in COVID-19 patients are correlated with inflammatory factors and organ function, and it can be used to predict organ injury.

JQ1, a BET-bromodomain inhibitor, inhibits human cancer growth and suppresses PD-L1 expression.

Most traditional cytotoxic chemotherapeutic agents have poor aqueous solubility and significant toxicity. Hence, there is a need to develop molecule-targeted drugs. Programmed death-ligand 1 (PD-L1) is associated with the prognosis of several cancer types, and blockade of PD-1/PD-L1 signaling increases the amplitude of anti-tumor immunity. In the present study, we investigated the effects of JQ1, a bromodomain and extraterminal-bromodomain inhibitor, on cell growth, and messenger RNA (mRNA) and protein levels of PD-L1 in renal cell carcinoma primary culture cells, and prostate, liver, and lung cancer cell lines. The results of the cell counting kit-8 assay suggested that JQ1 inhibits cell growth in a dose-dependent manner. The mRNA and protein levels of PD-L1 decreased in the primary culture of JQ1-treated renal carcinoma, prostate cancer, liver cancer, and lung cancer cell lines. In addition, the mRNA level of PD-L2 also decreased in the JQ1-treated cells. Overall, JQ1 might be a potential anti-tumor agent.

Clinical features of fatal severe fever with thrombocytopenia syndrome that is complicated by invasive pulmonary aspergillosis.

INTRODUCTION: Severe fever with thrombocytopenia syndrome (SFTS) has been prevalent in parts of Asia during recent years. However, SFTS with invasive pulmonary aspergillosis (IPA) is rare, and it is important to understand its clinical features. MATERIALS AND METHODS: Total four cases of SFTS with IPA are reviewed and detailing the disease progression, treatment options, and prognosis were summarized and analyzed. RESULTS: The patients with SFTS-associated IPA first presented with fever, gastrointestinal symptoms, thrombocytopenia, leukopenia, and multiple organ failure. After 1-2 weeks, the patients developed mild polypnea and wheezing rales, and quickly developed dyspnea and respiratory failure. Tracheal intubation was usually performed, but did not relieve the intractable airway spasm and pulmonary ventilation failure. Bronchoscopy confirmed that the antifungal treatment was ineffective and the aspergillosis had worsened. All patients died of type 2 respiratory failure caused by continued airway obstruction and spasticity. CONCLUSIONS: Given the high mortality rate in this series, there is a need for increased awareness of SFTS-associated IPA. Additional examinations should be performed in these cases, and early-stage antifungal treatment with organ support may be helpful.

Substance P Attenuates Hypoxia/Reoxygenation-Induced Apoptosis via the Akt Signalling Pathway and the NK1-Receptor in H9C2Cells.

BACKGROUND: Myocardial ischaemia/reperfusion (I/R) injury is a major cause of morbidity and mortality associated with coronary heart disease. During I/R injury, cardiomyocytes undergo cell death including apoptosis and necrosis with increased frequency, and this leads to compensatory cardiac hypertrophy, dysfunction, ventricular remodelling, and ultimately, heart failure. Accumulating evidence indicates that substance P is cardio-protective following I/R primarily due to its potent coronary vasodilator actions. However, its direct effect on cardiomyocytes in vitro remains controversial. METHODS: An hypoxia/reoxygenation (H/R)-induced cell death model was established to mimic I/R injury, in which the effect of substance P (SP) pretreatment on H9C2 cardiomyocytes and the mechanism of action were explored. RESULTS: Substance P was demonstrated to inhibit H/R-induced apoptosis. Phosphorylated-Akt (p-Akt) was decreased in H/R groups and was increased by SP pretreatment. Inhibition of p-Akt reduced the beneficial effects of SP in reducing apoptosis, whereas activation of Akt failed to provide additional improvement in the presence of SP. This suggests a key role for Akt in the process of reduced apoptosis by SP following H/R injury. In addition, the NK1-receptor antagonist prohibited the anti-apoptotic effect of SP. CONCLUSIONS: This study indicates that SP pretreatment attenuates H/R-induced apoptosis via the Akt signalling pathway and the NK1-receptor.

Detection and Pathologic Evaluation of Sentinel Lymph Nodes in the VX2 Tumor Model Using a Novel Ultrasound/Near-Infrared Dual-Modality Contrast Agent.

This study was conducted with the aim of developing a microbubble agent for near-infrared (NIR) fluorescence and ultrasound dual-modality contrast microbubbles applicable to imaging of sentinel lymph nodes in the VX2 rabbit tumor model. Specific ligands of phosphatidylserine (PS) and Cy7 NIR fluorescent dyes with long emission wavelengths (750-900 nm) were conjugated to the surface of ultrasound contrast microbubbles (MBs), termed Cy7 PS MBs. Ultrasound lymphography and NIR fluorescence imaging were performed using subcutaneous injection of Cy7 PS MBs to visualize the sentinel lymph node. Sentinel lymph node detection rates using the patent blue method, ultrasound lymphography and NIR fluorescence imaging were 95%, 79% and 95%, respectively, and sensitivity was 87%, 74% and 92%, respectively. With 2-D ultrasound, the diagnostic sensitivity for detection of sentinel lymph node metastases was 60% and the specificity was 74%, whereas Cy7 PS MB-enhanced ultrasound had a sensitivity of 80% and a specificity of 87%. The results indicate that dual-modality Cy7 PS MBs combined with ultrasound lymphography and NIR fluorescence may be useful in the detection of normal and metastasized sentinel lymph nodes.