Major Characteristics of Severity and Mortality in Diabetic Patients With COVID-19 and Establishment of Severity Risk Score.

Objectives: Diabetes is a risk factor for poor COVID-19 prognosis. The analysis of related prognostic factors in diabetic patients with COVID-19 would be helpful for further treatment of such patients. Methods: This retrospective study involved 3623 patients with COVID-19 (325 with diabetes). Clinical characteristics and laboratory tests were collected and compared between the diabetic group and the non-diabetic group. Binary logistic regression analysis was applied to explore risk factors associated in diabetic patients with COVID-19. A prediction model was built based on these risk factors. Results: The risk factors for higher mortality in diabetic patients with COVID-19 were dyspnea, lung disease, cardiovascular diseases, neutrophil, PLT count, and CKMB. Similarly, dyspnea, cardiovascular diseases, neutrophil, PLT count, and CKMB were risk factors related to the severity of diabetes with COVID-19. Based on these factors, a risk score was built to predict the severity of disease in diabetic patients with COVID-19. Patients with a score of 7 or higher had an odds ratio of 7.616. Conclusions: Dyspnea is a critical clinical manifestation that is closely related to the severity of disease in diabetic patients with COVID-19. Attention should also be paid to the neutrophil, PLT count and CKMB levels after admission.

Inhaled budesonide prevents acute mountain sickness in young Chinese men.

BACKGROUND: Oral glucocorticoids can prevent acute mountain sickness (AMS). Whether inhaled budesonide (BUD) can prevent AMS remains unknown. OBJECTIVE: Our aim was to investigate the effectiveness of BUD in AMS prevention. METHODS: Eighty subjects were randomly assigned to receive budesonide (BUD, inhaled), procaterol tablet (PT), budesonide/formoterol (BUD/FM, inhaled), or placebo tablet (n = 20 in each group). Subjects were treated for 3 days before ascending from 500 m to 3700 m within 2.5 h by air. Lake Louis AMS questionnaire, blood pressure, heart rate, and oxygen saturation (SpO2) were examined at 20, 72, and 120 h after high-altitude exposure. Pulmonary function was measured at 20 h after exposure. RESULTS: Compared with placebo, BUD significantly reduced the incidence of AMS (70% vs. 25% at 20 h, p < 0.05; both 10% vs. 5% at 72 and 120 h, both p > 0.05) without side effects. The relative risk was 0.357, and the risk difference was 0.45. Mean SpO2 was higher in BUD, BUD/FM, and PT groups than in the placebo group at 20 h (p < 0.05). SpO2 in all 80 subjects dropped after ascent (98.1% to 88.12%, p < 0.01) and increased gradually, but it was still lower at 120 h than at baseline (92.04% vs. 98.1%, p < 0.01). Pulmonary function did not differ among the four groups at 20 h. CONCLUSION: BUD can prevent AMS without side effects. The alleviation of AMS may be related to increased blood oxygen levels rather than pulmonary function.

Hypoxia-inducible factor 1 promoter-induced JAB1 overexpression enhances chemotherapeutic sensitivity of lung cancer cell line A549 in an anoxic environment.

The presence of lung cancer cells in anoxic zones is a key cause od chemotherapeutic resistance. Thus, it is necessary to enhance the sensitivity of such lung cancer cells. However, loss of efficient gene therapeutic targeting and inefficient objective gene expression in the anoxic zone in lung cancer are dilemmas. In the present study, a eukaryotic expression plasmid pUC57-HRE-JAB1 driven by a hypoxia response elements promoter was constructed and introduced into lung cancer cell line A549. The cells were then exposed to a chemotherapeutic drug cis-diamminedichloroplatinum (C-DDP). qRT-PCR and western blotting were used to determine the mRNA and protein level and flow cytometry to examine the cell cycle and apoptosis of A549 transfected pUC57-HRE-JAB1. The results showed that JAB1 gene in the A549 was overexpressed after the transfection, cell proliferation being arrested in G1 phase and the apoptosis ratio significantly increased. Importantly, introduction of pUC57-HRE-JAB1 significantly increased the chemotherapeutic sensitivity of A549 in an anoxic environment. In conclusion, JAB1 overexpression might provide a novel strategy to overcome chemotherapeutic resistance in lung cancer.

Pretreatment with anti-flagellin serum delays acute lung injury in rats with sepsis.

OBJECTIVE: This study examined the reduction of sepsis-induced ALI by inhibition of flagellin-stimulated TLR5 signaling. METHODS: Rats were randomly divided into three groups: one group served as the sham-operated group (control group), and the other two groups received the induction of sepsis (sepsis and treatment groups). The treatment group was injected with anti-flagellin serum before induction of sepsis. At 2, 4, 6, 12, 24, and 48 h following induction of sepsis (six time-point subgroups, n = 10 per subgroup), arterial PaO(2), wet/dry (W/D) lung weight ratios, levels of serum and BALF flagellin and TNF-α, pulmonary pathological alterations, and TLR5 mRNA expression in the lungs were examined. RESULTS: Compared to sham-operated rats, septic rats had: increased levels of serum and BALF flagellin at 6, 12, 24, and 48 h; reduced arterial PaO(2); elevated W/D lung weight ratio; increased serum and BALF TNF-α levels; and up-regulated TLR5 mRNA expression at 12, 24, and 48 h (P < 0.01). Pretreatment with anti-flagellin serum, however, significantly inhibited sepsis-associated declines in arterial PaO(2), increased W/D lung weight ratios, elevated serum and BALF TNF-α levels, and up-regulated TLR5 mRNA expression at 24 and 48 h (P < 0.01). CONCLUSION: Neutralizing the actions of circulating flagellin with anti-flagellin serum delayed the development of ALI in rats with sepsis.

[The effects of Ad-Gax transfection on apoptosis and related gene expression in pulmonary arterial smooth muscle cells in hypoxic rat model].

OBJECTIVE: To explore the effects of growth arrest-specific homeobox (Gax) transfection on apoptosis and expressions of Bcl-2 and Bax proteins of rat pulmonary arterial smooth muscle cells (PASMCs) exposed to hypoxia. METHODS: PASMCs were transfected with Gax gene by a replication-deficient adenovirus expressing the hemagglutinin-tagged Gax cDNA (Ad-Gax). After exposure to normal oxygenation (21% O(2)) or hypoxia (2.5% O(2)) for 2 h, 6 h, 12 h, 24 h and 48 h, apoptosis was observed by transmission electronic microscope and TUNEL-positive staining. The expressions of Bcl-2 and Bax proteins in PASMCs were detected by immunocytochemistry. RESULTS: Before Ad-Gax transfection, none or few of TUNEL-positive PASMCs were detected. After Ad-Gax transfection, the PASMCs unexposed to hypoxia displayed none or few TUNEL-positive stain, while the PASMCs exposed to hypoxia displayed a marked increase in TUNEL-positive stain, especially in cells exposed to hypoxia for 24 h to 48 h. The ratio of apoptosis of PASMCs at normoxic, hypoxia 2 h, 6 h, 12 h, 24 h and 48 h were (9.11 +/- 1.21)%, (34.13 +/- 1.02)%, (39.12 +/- 0.43)%, (50.09 +/- 0.13)%, (60.04 +/- 1.12)% and (55.47 +/- 0.03)% (P < 0.01), respectively. Before Ad-Gax transfection, the level of Bax protein showed no significant increase in PASMCs exposed to hypoxia, while that of Bcl-2 protein increased significantly, as compared to that in PASMCs under normoxic condition. The average optical density (AOD) of Bcl-2 was 2.31 +/- 0.12, 2.35 +/- 0.23, 2.49 +/- 0.27, 2.51 +/- 0.19, 2.54 +/- 0.25 and 2.53 +/- 0.20 at normoxic, hypoxia for 2 h, 6 h, 12 h, 24 h and 48 h before Ad-Gax transfection, respectively (P < 0.05, P < 0.01). After Ad-Gax transfection to PASMCs exposed to hypoxia, Bax protein increased; the AOD of Bax was 3.82 +/- 0.38, 3.12 +/- 0.42, 3.53 +/- 0.61, 4.52 +/- 0.23, 4.25 +/- 0.76 and 4.03 +/- 0.38 at normoxic, hypoxia for 2 h, 6 h, 12 h, 24 h and 48 h (P < 0.01), respectively. But Bcl-2 protein decreased significantly; the AOD of Bcl-2 was 9.11 +/- 1.21, 34.13 +/- 1.02, 39.12 +/- 0.43, 50.09 +/- 0.13, 60.04 +/- 1.12 and 55.47 +/- 0.03, respectively (P < 0.01). After Ad-Gax transfection, the Bcl-2/Bax ratio was negatively correlated with the rate of apoptotic PASMCs (r = -0.53, P < 0.01). CONCLUSION: Ad-Gax transfection induced PASMC apoptosis after exposure to hypoxia. A possible mechanism is that Gax can downregulate Bcl-2 expression and upregulate Bax expression, especially by decrease of the Bcl-2/Bax ratio.