The Role of the Tissue Perfusion Index in Predicting Disease Severity and Prognosis in Patients with Severe and Critical COVID-19.

OBJECTIVES: The study investigated whether percutaneous partial pressure of oxygen (PtcO2), percutaneous partial pressure of carbon dioxide (PtcCO2), and the derived tissue perfusion index (TPI) can predict the severity and short-term outcomes of severe and critical COVID-19. DESIGN: Prospective observational study conducted from January 1, 2023 to February 10, 2023. SETTING: A teaching hospital specializing in tertiary care in Nanjing City, Jiangsu Province, China. PARTICIPANTS: Adults (≥18 years) with severe and critical COVID-19. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The general information and vital signs of the patients were collected. The PtcO2 and PtcCO2 were monitored in the left dorsal volar. The ratio of TPI was defined as the ratio of PtcO2/fraction of inspired oxygen (FiO2) to PtcCO2. Mortality at 28 was recorded. The ability of the TPI to assess disease severity and predict prognosis was determined. ENDPOINT: Severity of the disease on the enrollment and mortality at 28. RESULTS: A total of 71 patients with severe and critical COVID-19, including 40 severe and 31 critical cases, according to the COVID-19 treatment guidelines published by WHO, were recruited. Their median age was 70 years, with 56 (79%) males. The median SpO2/FiO2, PtcO2, PtcCO2, PtcO2/ FiO2, and TPI values were 237, 61, 42, 143, and 3.6 mm Hg, respectively. Compared with those for severe COVID-19, the TPI, PtcO2/ FiO2, SpO2/FiO2, and PtcO2 were significantly lower in critical COVID-19, while the PtcCO2 was significantly higher. After 28 days, 26 (37%) patients had died. TPI values < 3.5 were correlated with more severe disease status (AUC 0.914; 95% CI: 0.847-0.981, P < 0.001), and TPI < 3.3 was associated with poor outcomes (AUC 0.937; 95% CI 0.880-0.994, P < 0.001). CONCLUSIONS: The tissue perfusion index (TPI), PtcCO2, and PtcO2/ FiO2 can predict the severity and outcome of severe and critical COVID-19.

Inhibitory Smads suppress pancreatic stellate cell activation through negative feedback in chronic pancreatitis.

BACKGROUND: Activation of pancreatic stellate cells (PSCs) is a key cause of chronic pancreatitis (CP), while inhibition of transforming growth factor-ß (TGF-ß) signaling renders PSCs inactive. Inhibitory Smads (I-Smads) impede TGF-ß intracellular signaling and may provide a way to alleviate CP. Thus, we aimed to investigate the molecular mechanism of I-Smads in CP animals and freshly-isolated PSCs. METHODS: Sixteen male C57BL/6 mice were randomly divided into two groups; a control group (treated with saline) and a CP group (treated with caerulein) for 6 weeks. Masson's staining was performed to identify fibrosis, and immunohistochemistry (IHC) was performed to measure the levels of Smad6 between the two groups. An improved method derived from internal digestion was used to isolate PSCs from male Sprague Dawley rats. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence staining were used to measure the messenger ribonucleic acid (mRNA) and protein levels of alpha-smooth muscle actin (α-SMA). Plasmids of I-Smads or SB431542 were transfected into freshly-isolated PSCs, and relative mRNA levels of marker genes were quantified by qRT-PCR. The two-tailed Student's t-test was performed to assess significance. RESULTS: The Smad6 protein level was significantly higher in the pancreas tissue of CP mice compared to the control group. A large number of PSCs were isolated from rat pancreas using an improved isolating method and were confirmed by quiescent and active PSC markers including cluster differentiation antigen 133 (CD133), perilipin 2 (Plin2), α-SMA, Desmin, and collagen 1 (Col1). The mRNA levels of both Smad6 and Smad7 were down-regulated during freshly-isolated PSC activation. Over-expression of both Smad6 and Smad7 in freshly-isolated PSC reduced the mRNA level of α-SMA, glial fibrillary acidic protein (GFAP), Desmin, Col1, Col3, and fibronectin 1 (Fn1) significantly. SB431542 reduced the mRNA level of α-SMA, Col1, Col3, and Fn1 significantly in freshly-isolated PSCs. CONCLUSIONS: This study demonstrated that CP promoted the expression of I-Smads, which suppressed the activation of freshly-isolated PSCs via a negative feedback loop.

A natural biopreservative: Antibacterial action and mechanisms of Chinese Litsea mollis Hemsl. extract against Escherichia coli DH5α and Salmonella spp.

Chemical preservatives have potential safety hazards, which may pose threats to human health. Safer biopreservatives are therefore urgently required. This study investigated the bacteriostatic activity and mechanism of Litsea mollis Hemsl. essential oil against Escherichia coli DH5α and Salmonella spp. Antibacterial activity of Litsea mollis Hemsl. essential oil 9 (LMEO9) against E. coli DH5α was observed (zone of inhibition was 5.0 ± 0.2 mm; minimum inhibitory concentration was 0.05%). Increases in electrolyte, nucleic acid, and alkaline phosphatase leakage in LMEO9-treated bacteria suggested that the cell envelope had been damaged. Scanning and transmission electron microscopy also demonstrated morphological alterations and content leakage during LMEO9 treatment. According to the kill-time analysis and propidium iodide uptake assay, LMEO9 led to cell death. These results demonstrated that LMEO9, which could affect bacterial cell envelope structural integrity, is a low-cost biopreservative that could be useful for the dairy industry and in fresh storage.