Mechanisms of action of berberine hydrochloride in planktonic cells and biofilms of Pseudomonas aeruginosa.

The increasing prevalence of extensively drug-and pan-drug-resistant Pseudomonas aeruginosa is a major concern for global public health. Therefore, it is crucial to develop novel antimicrobials that specifically target P. aeruginosa and its biofilms. In the present study, we determined that berberine hydrochloride inhibited the growth of planktonic bacteria as well as prevented the formation of biofilms. Moreover, we observed downregulation in the expression of pslA and pelA biofilm-related genes. Compared with existing antibiotics, berberine hydrochloride exhibits multiple modes of action against P. aeruginosa. Our findings suggest that berberine hydrochloride exerts its antimicrobial effects by damaging bacterial cell membranes, generating reactive oxygen species (ROS), and reducing intracellular adenosine triphosphate (ATP) levels. Furthermore, berberine hydrochloride showed minimal cytotoxicity and reduced susceptibility to drug resistance. In a mouse model of peritonitis, it significantly inhibited the growth of P. aeruginosa and exhibited a strong bacteriostatic action. In conclusion, berberine hydrochloride is a safe and effective antibacterial agent that inhibits the growth of P. aeruginosa.

Clinical characteristics of venous thromboembolism onset from severe high altitude pulmonary edema in plateau regions.

BACKGROUND: To investigate venous thromboembolism (VTE) in hospitalized patients with severe high altitude pulmonary edema (HAPE), we performed a single center retrospective study to evaluate its clinical characteristics, prognosis, and potential thromboprophylaxis strategies in a large referral and treatment center in plateau regions. METHODS: We studied a total of 18 patients with severe HAPE from January 1, 2012 to December 31, 2021. Demographic and clinical data, laboratory data, including ultrasound scans of the lower extremities and cardiac ultrasound, and computed tomographic pulmonary angiography (CTPA) variables were obtained, and comparisons were made between groups with and without VTE. RESULTS: Of the 18 patients hospitalized with severe HAPE (age 43 (range, 34-54) years, 14 [77.8%] men), 7 patients developed VTE (38.9%), including 5 with deep vein thrombosis (DVT) and pulmonary embolism (PE), 2 of whom had DVT only. Eighteen patients are all firstly rapid ascent to high altitudes which the mean altitude was 3700 m (3656-4050 m). Compared with patients who did not have VTE, patients with VTE had a longer time in hospital (13 [11, 19] versus 9 [7, 12]; P = 0.027), respiratory failure (6 [85.7%] versus 2 [18.2%]; P = 0.013), the shortened APTT (21.50 [19.00, 27.50] versus 26.30 [24.80, 30.10]; P = 0.044) and the higher level of D-dimer (7.81 [4.62, 9.60] versus 2.90 [1.75, 3.37]; P = 0.003). The proportion of thromboprophylaxis is too low in our cohort which 2 of 18 (11.1%) patients were given VTE prophylaxis. There was no statistically significant difference between the VTE and non-VTE groups (0 [0.0%] versus 2 [18.2%]; P = 0.497). CONCLUSIONS: The prevalence of VTE is high in hospitalized patients with severe high altitude pulmonary edema (HAPE). Prophylaxis for venous thromboembolism may be protective in severe HAPE patients after admission. Our data seem to suggest that VTE is probably an additional prognostic factors in patients with severe HAPE.