Accumulated Clinical Experiences from Successful Treatment of 1377 Severe and Critically Ill COVID-19 Cases.

In late December 2019, COVID-19 was firstly recognized in Wuhan, China and spread rapidly to all of the provinces of China. The West Campus of Wuhan Union Hospital, the designated hospital to admit and treat the severe and critically ill COVID-19 cases, has treated a large number of such patients with great success and obtained lots of valuable experiences based on the Chinese guideline (V7.0). To standardize and share the treatment procedures of severe and critically ill cases, Wuhan Union Hospital has established a working group and formulated an operational recommendation, including the monitoring, early warning indicators, and several treatment principles for severe and critically ill cases. The treatment experiences may provide some constructive suggestions for treating the severe and critically ill COVID-19 cases all over the world.

Up-regulation of cullin7 promotes proliferation and migration of pulmonary artery smooth muscle cells in hypoxia-induced pulmonary hypertension.

It has well been demonstrated that E3 ubiquitin ligase cullin7 plays important roles in cancer cell growth control via down-regulating p53 expression. The noncanonical function or the pathogenic role of p53 has more recently been implicated in pulmonary vascular remodeling. Therefore, whether cullin7 participates in hypoxia-induced pulmonary vascular remodeling deserves to be elucidated. The present study found that hypoxia up-regulated the expression of cullin7 mRNA and protein in pulmonary arteries and pulmonary artery smooth muscle cells, and knockdown of cullin7 inhibited hypoxia-induced proliferation and migration of pulmonary artery smooth muscle cells and reversed hypoxia-induced inhibition of p53 expression. Notably, administration of proteasome inhibitor MG132 significantly inhibited the expression of cullin7 and up-regulated the expression of p53 in pulmonary arteries concomitantly with improvement of hypoxia-induced pulmonary vascular remodeling. Our study demonstrated that hypoxia induced up-regulation of cullin7 expression resulting to the proliferation and migration of pulmonary artery smooth muscle cells via down-regulating p53 expression, which contributed to pulmonary vascular remodeling.

LOX-1 promotes right ventricular hypertrophy in hypoxia-exposed rats.

AIM: Chronic hypoxia leads to right ventricular hypertrophy (RVH). RVH is believed to result from hypoxia-induced pulmonary hypertension. However, if hypoxia impacts RVH directly awaits clarification. Hypoxia triggers oxidative stress, and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) mediates reactive oxygen species (ROS) generation in different cells. Therefore, this study aims to explore whether LOX-1-mediated oxidative stress accounts for hypoxia-induced RVH. MAIN METHODS: Rats developed RVH after 3weeks of hypoxia (10% O2). Immunofluorescence staining was performed to evaluate H9C2 cell hypertrophy induced by hypoxia (3% O2). Real-time PCR and Western-blot were performed to assess LOX-1, NADPH oxidases (NOX), collagen I/III, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) expression. DCFH-DA staining was performed to measure ROS generation. KEY FINDINGS: Hypoxia induced RVH and cardiac fibrosis in rats, as indicated by enlarged cardiomyocytes and deposition of extracellular matrix. Interestingly, hypoxia treatment directly induced H9C2 cardiomyocyte hypertrophy, implying direct effects of hypoxia on cell hypertrophy. Rat and H9C2 hypertrophy model revealed that cell hypertrophy was accompanied by marked increase in LOX-1 expression. Knockdown of LOX-1 significantly ameliorated H9C2 cell hypertrophy. Mechanistically, hypoxia induced prominent oxidative stress in rat right ventricles and H9C2 cells, most likely as a result from increased expression of NOX2/4, contributing to RVH. Knockdown of LOX-1 significantly attenuated H9C2 cell oxidative stress, with a concomitant decrease in NOX2/4 expression. SIGNIFICANCE: LOX-1/NOX/ROS pathway could represent a novel mechanism underlying hypoxia-induced RVH. Therapeutic targeting of LOX-1 would be exploited to treat RVH owing to chronic hypoxia exposure.

MiR-590-5p-meidated LOX-1 upregulation promotes Angiotensin II-induced endothelial cell apoptosis.

BACKGROUND: Endothelial cell apoptosis contributes to cardiovascular diseases such as hypertension, atherosclerosis. MicroRNA regulates endothelial cell function but its role in endothelial cell apoptosis remains to be fully elucidated. This study aims to investigate the role of miR-590-5p in endothelial cell apoptosis and dissect the underlying mechanisms. METHODS: Flow cytometric analysis, Hoechst 33258 staining and Western blotting were performed to evaluate human umbilical vein endothelial cell (HUVEC) apoptosis induced by Angiotensin (Ang) II. Western blotting and real-time quantitative PCR were conducted to assess the expression of LOX-1. DCFH-DA staining was carried out to measure the generation of reactive oxygen species (ROS). RESULTS: Ang II-induced HUVEC apoptosis was accompanied by downregulation of miR-590-5p; administration of miR-590-5p mimics attenuated HUVEC apoptosis and decreased ROS generation, as indicated by reduced fraction of apoptotic HUVECs and decreased caspase-3 activity. LOX-1 expression was increased by Ang II, and miR-590-5p mimics reduced LOX-1 expression in HUVECs in the absence or presence of Ang II. Pharmacologic or genetic block of LOX-1 with small interference RNA or TS92 (LOX-1 neutralizing antibody) significantly ameliorated HUVEC apoptosis, as evidenced by reduced number of apoptotic HUVECs, inhibited caspase-3 activation and suppressed mitochondrial cytochrome C release. Moreover, LOX-1 siRNA or TS92 treatment dramatically reduced ROS production in HUVECs treated with Ang II. CONCLUSION: Our data demonstrated that miR-590-5p downregulation promoted Ang II-induced endothelial cell apoptosis by elevating LOX-1 expression and consequently increasing ROS generation. Thus, restoration of miR-590-5p or block of LOX-1 could be therapeutically exploited to alleviate endothelial cell apoptosis.

A comparative study of the urinary trypsinogen-2, trypsinogen activation peptide, and the computed tomography severity index as early predictors of the severity of acute pancreatitis.

BACKGROUND/AIMS: The aim of the study was to establish the value of urinary trypsinogen-2 in predicting the severity of acute pancreatitis (AP) and to compare it with the accuracy of the urinary trypsinogen activation peptide (TAP) and the computed tomography severity index (CTSI). METHODOLOGY: The study population consisted of 187 consecutive patients with AP, of whom 38 had severe disease. The predictive values of urinary trypsinogen-2, TAP and CTSI were assessed within 24 h of the onset of symptoms. RESULTS: The mean values of predictive markers in the mild and severe pancreatitis groups were: urinary trypsinogen-2, 59/90 and 25/13 (p < 0.001); urinary TAP, 13.2 +/- 3.3nmol/l and 66.2 +/- 19.3 nmol/l (p < 0.001); and computed tomography severity index, 1.42 +/- 1.1 and 5.31 +/- 2.6 (p < 0.001). The sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios were calculated for the urinary trypsinogen-2 (65.7%, 66.4%, 33.3%, 88.4%, 1.9, and 0.51), for TAP (greater than 35 nmol/l: 63.2%, 65.8%, 32.0%, 87.5%, 1.9, and 0.58) and for CTSI (greater than 3: 47.4%, 95.3%, 69.2%, 87.7%, 9.0 and 0.55). To differentiate between severe and mild AP, urinary trypsinogen-2 (AUC 0.724) was slightly better than TAP (AUC 0.722), and they were both clearly better than CTSI (AUC 0.597) (p < 0.05). Urinary trypsinogen-2 had significantly lower cost (p < 0.001) than TAP and computed tomography. CONCLUSION: Urinary trypsinogen-2 was superior to CTSI and was as good as or even better than urinary TAP in the early prediction of severity in AP. This suggests that this simple and quick method deserves routine clinical application.

[Protective effects of tetramethylpyrazine on rat myocardial cells infected by Coxsackie virus B3 and its signal transduction mechanism].

OBJECTIVE: To study the protective effects of tetramethylpyrazine (TMPZ) on rat myocardial cells infected by Coxsackie virus B3 (CVB3) and its signal transduction mechanism. METHODS: The cultured myocardial cells of neonatal Sprague-Dawley rats were randomly treated with CVB3, CVB3+TMPZ (100 micromol/L), TMPZ (100 micromol/L) (negative control) or DMEM (blank control). After treatment, the beating rate of myocardial cells and the LDH activity in the culture fluid were measured. Cell viability was ascertained with MTT assay. Western blot was used to study the expression of nuclear factor kappa-B (NF-kappaB) protein in myocardial cells. RESULTS: The beating rate of myocardial cells in the untreated CVB3 infection group was significantly lower than that in the TMPZ-treated CVB3 infection group (32.0+/-3.6 bpm vs 84.3+/-3.5 bpm, P<0.01). The LDH activity and NF-kappaB expression in the TMPZ-treated CVB3 infection group was significantly reduced when compared with untreated CVB3 infection group (P<0.05, P<0.01, respectively). Cell viability 7 days after CVB3 infection in the TMPZ-treated group was higher than that in the untreated CVB3 infection group (86.7+/-2.7% vs 35.3+/-3.4%; P<0.01). CONCLUSIONS: TMPZ can provide protective effects on rat myocardial cells infected by CVB3, possibly by an inhibition of the activity of NF-kappaB in myocardial cells.