Time-varying intensity of oxygen exposure is associated with mortality in critically ill patients with mechanical ventilation.

BACKGROUND: There is no consensus exists regarding the association between oxygen exposure (arterial oxygen tension or fraction of inspired oxygen) and outcomes for patients with mechanical ventilation. Additionally, whether the association remains persistent over time is unknown. We aimed to explore the association between exposure to different intensities of oxygen exposure over time and 28-day mortality in patients with mechanical ventilation. METHODS: We obtained data from the Medical Information Mart for Intensive Care IV (MIMIC-IV), which included adult (≥ 18 years) patients who received invasive mechanical ventilation for at least 48 h. We excluded patients who received extracorporeal membrane oxygenation (ECMO) or who initiated ventilation more than 24 h after ICU admission. The primary outcome was 28-day mortality. Piece-wise exponential additive mixed models were employed to estimate the strength of associations over time. RESULTS: A total of 7784 patients were included in the final analysis. Patients had a median duration of invasive mechanical ventilation of 8.1 days (IQR: 3.8-28 days), and the overall 28-day mortality rate was 26.3%. After adjustment for baseline and time-dependent confounders, both daily time-weighted average (TWA) arterial oxygen tension (PaO2) and fraction of inspired oxygen (FiO2) were associated with increased 28-day mortality, and the strength of the association manifested predominantly in the early-middle course of illness. A significant increase in the hazard of death was found to be associated with daily exposure to TWA-PaO2 ≥ 120 mmHg (Hazard ratio 1.166, 95% CI 1.059-1.284) or TWA-FiO2 ≥ 0.5 (Hazard ratio 1.496, 95% CI 1.363-1.641) during the entire course. A cumulative effect of harmful exposure (TWA-PaO2 ≥ 120 mmHg or TWA-FiO2 ≥ 0.5) was also observed. CONCLUSION: PaO2 and FiO2 should be carefully monitored in patients with mechanical ventilation, especially during the early-middle course after ICU admission. Cumulative exposure to higher intensities of oxygen exposure was associated with an increased risk of death.

Risk and protective factors for chronic pain following inguinal hernia repair: a retrospective study.

PURPOSE: A large proportion of patients experience chronic post-surgical pain (CPSP) following inguinal hernia repair surgery. The aim of this study was to investigate the predictive risk factors and protective factors for CPSP following inguinal hernia surgery. METHODS: After institutional ethics approval was obtained, we conducted a retrospective observational case-control study including a total of 236 adult patients undergoing elective inguinal hernia repair at a single tertiary medical center from 2014 to 2015. Preoperative and postoperative variables were collected from electronic medical records. Binary logistic analysis was used to determine the association between CPSP and clinical factors and built a CPSP risk model. RESULTS: The incidence of CPSP was 14.4%. Bilateral inguinal hernia repair (OR 4.44; 95% CI 1.62 to 12.17; p = 0.004), preoperative pain (OR 2.57; 95% CI 1.14 to 5.79; p = 0.023), preoperative anxiety (OR 1.05; 95% CI 1.01 to 1.09; p = 0.018), and relatively high intensity of acute pain at 1 week after the surgery (OR 1.40; 95% CI 1.03 to 1.91; p = 0.031) were the risk factors for CPSP while low-dose ketamine at anesthesia induction (OR 0.42; 95% CI 0.18 to 0.98; p = 0.044) was the protective factor for CPSP in patients undergoing inguinal hernia repair. CONCLUSIONS: These results indicated that bilateral inguinal hernia repair, preoperative pain, preoperative anxiety, and acute pain at 1 week after the surgery were the independent risk factors for CPSP while low-dose ketamine was the protective factor. These findings may assist with primary prevention by allowing clinicians to screen for individuals with the risk of CPSP.

Comparative transcriptome analysis revealing the potential mechanism of seed germination stimulated by exogenous gibberellin in Fraxinus hupehensis.

BACKGROUND: Fraxinus hupehensis is an endangered tree species that is endemic to in China; the species has very high commercial value because of its intricate shape and potential to improve and protect the environment. Its seeds show very low germination rates in natural conditions. Preliminary experiments indicated that gibberellin (GA3) effectively stimulated the seed germination of F. hupehensis. However, little is known about the physiological and molecular mechanisms underlying the effect of GA3 on F. hupehensis seed germination. RESULTS: We compared dormant seeds (CK group) and germinated seeds after treatment with water (W group) and GA3 (G group) in terms of seed vigor and several other physiological indicators related to germination, hormone content, and transcriptomics. Results showed that GA3 treatment increases seed vigor, energy requirements, and trans-Zetain (ZT) and GA3 contents but decreases sugar and abscisic acid (ABA) contents. A total of 116,932 unigenes were obtained from F. hupehensis transcriptome. RNA-seq analysis identified 31,856, 33,188 and 2056 differentially expressed genes (DEGs) between the W and CK groups, the G and CK groups, and the G and W groups, respectively. Up-regulation of eight selected DEGs of the glycolytic pathway accelerated the oxidative decomposition of sugar to release energy for germination. Up-regulated genes involved in ZT (two genes) and GA3 (one gene) biosynthesis, ABA degradation pathway (one gene), and ABA signal transduction (two genes) may contribute to seed germination. Two down-regulated genes associated with GA3 signal transduction were also observed in the G group. GA3-regulated genes may alter hormone levels to facilitate germination. Candidate transcription factors played important roles in GA3-promoted F. hupehensis seed germination, and Quantitative Real-time PCR (qRT-PCR) analysis verified the expression patterns of these genes. CONCLUSION: Exogenous GA3 increased the germination rate, vigor, and water absorption rate of F. hupehensis seeds. Our results provide novel insights into the transcriptional regulation mechanism of effect of exogenous GA3 on F. hupehensis seed germination. The transcriptome data generated in this study may be used for further molecular research on this unique species.

MicroRNA156 amplifies transcription factor-associated cold stress tolerance in plant cells.

MicroRNAs may increase cold stress tolerance by regulating stress-related signal transduction pathways and by modulating the expression of transcription factors. However, the molecular mechanism by which microRNAs enhance cold stress tolerance is not fully understood. Here, we report that overexpression of rice microRNA156 (OsmiR156) results in increased cell viability and growth rate under cold stress in Arabidopsis, pine, and rice. OsmiR156 increases cold stress tolerance by targeting OsSPL3. OsSPL3 positively regulates the expression of OsWRKY71, a negative regulator of the transcription factors OsMYB2 and OsMYB3R-2. OsMYB2 counteracts cold stress by activating the expression of the stress-response genes OsLEA3, OsRab16A, and OsDREB2A. OsMYB3R-2 counteracts cold stress by activating the expression of OsKNOLLE2, OsCTP1, OsCycB1.1, OsCycB2.1, and OsCDC20.1. In OsmiR156 transgenic rice cell lines, the transcript levels of OsLEA3, OsRab16A, OsDREB2A, OsKNOLLE2, OsCTP1, OsCycB1.1, OsCycB2.1, and OsCDC20.1 were increased by OsWRKY71 knockdown and inversely regulated by OsWRKY71 overexpression, indicating that OsmiR156 enhances cold stress tolerance by regulating the expression of transcription factor genes in plant cells. These results will increase our understanding of microRNA-related cold stress tolerance in different plant species, including monocotyledonous, dicotyledonous, and gymnosperm plant species, and will be valuable in plant molecular biotechnology.

TRPM8 overexpression suppresses hepatocellular carcinoma progression and improves survival by modulating the RTP3/STAT3 pathway.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a malignant tumour associated with high morbidity and mortality rates worldwide. Recently, TRPM8 was reported to play an important role in tumour progression. However, the precise role of TRPM8 in HCC remains unclear. In this study, we explored the expression levels, molecular functions and underlying mechanisms of TRPM8 in HCC. METHODS: Tissue samples were used to analyse the expression of TRPM8 to assess its diagnostic value for prognosis. Cell Counting Kit-8, EdU and colony formation assays were performed to evaluate the effects of TRPM8 on cell proliferation, whereas the Transwell assay was used to assess cell migration and invasion. The role of TRPM8 in vivo was evaluated using a mouse subcutaneous xenograft tumour model. We performed PPI network analyses to understand the possible mechanisms of TRPM8 action. RESULTS: TRPM8 expression was decreased in HCC tissues and was correlated with histological grade and poor patient prognosis. Functionally, TRPM8 repressed the proliferation and metastasis of HCC cells both in vitro and in vivo by modulating the RTP3/STAT3 signalling pathway. CONCLUSION: Our findings underscore the critical role of the TRPM8-RTP3-STAT3 axis in maintaining the malignant progression of HCC. Moreover, our study demonstrates that AD80 is involved in anti-tumour processes by upregulating the expression of TRPM8.