Sepsis often causes diaphragm contractile dysfunction. Endoplasmic reticulum (ER) stress has been implicated in muscle contractile dysfunction. However, it remains unknown if ER stress occurs in the diaphragm during sepsis. In the present study, rats were divided into 4 groups and received placebo or one of three durations of endotoxin treatment (24, 48 h and 7 days). Isometric contractile force of the diaphragm was measured and lung wet-to-dry ratio (W/D) was calculated. Hematoxylin and eosin (H&E) staining of lung tissue was performed and electron microscopy assessed ER damage in the diaphragm during sepsis. The mRNA and protein expression of glucose‑regulated protein 78 kDa (GRP78), glucose-regulated protein 94 kDa (GRP94), C/EBP homologous protein (CHOP), endoplasmic reticulum protein 44 (ERP44), protein disulfide-isomerase like protein (ERP57) and protein disulfide isomerase family A member 4 (ERP72) in diaphragm muscles were measured using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The level of cleaved caspase-12 was analyzed by western blot analysis. The results demonstrated that sepsis increased lung W/D. H&E staining revealed that sepsis caused alveolar congestion, hemorrhage and rupture. Swollen and distended ER was observed using electron microscopy during sepsis and decreased diaphragm contractile function was also observed. The expression levels of ER stress markers (GRP78, GRP94, CHOP, ERP44, ERP57 and ERP72) and the level of cleaved caspase‑12 were significantly elevated in septic rats compared with control rats, particularly in the 48 h group. In conclusion, the present study indicated that weakened diaphragm contraction and damaged ER in septic rats was associated with increased expression of ER stress markers.

Weakened diaphragm contraction in the septic rats was associated with reduced mRNA and protein expression of DHPRα1s and RyR1, the isoforms of skeletal muscles.

1. Paraquat (PQ) is an organic nitrogen heterocyclic herbicide that is widely used in agriculture throughout the world. Numerous studies have reported PQ intoxication on humans. 2. In this study, we established a rat lung injury model induced by PQ and evaluated the intervention effect of rapamycin on the model, exploring the pathogenesis of PQ on lung injury as well as therapeutic effects of rapamycin on PQ-induced lung injury. 3. A rat lung injury model was established by gavage of PQ, and rapamycin was used to treat the model animals with PQ-induced lung injury. Different physiological indices were measured through Western blot and real-time polymerase chain reaction to evaluate the effect of rapamycin on the PQ-induced lung injury. 4. The analyses showed that application of rapamycin could significantly reduce the lung injury damage caused by PQ, with lung tissue wet-dry weight ratio, pathological features, compositions in serum, protein in bronchoalveolar lavage fluid and other indices being significantly improved after the injection of rapamycin. 5. It was inferred that the use of rapamycin could improve the PQ-induced lung injury through inhibiting the activity of mTOR. And we expected the use of rapamycin to be a potential treatment method for the PQ intoxication in future.

Information on the interactive effects of methylprednisolone, controlled mechanical ventilation (CMV), and assisted mechanical ventilation (AMV) on diaphragm function is sparse. Sedated rabbits received 2 days of CMV, AMV, and spontaneous breathing (SB), with either methylprednisolone (MP; 60 mg/kg/day intravenously) or saline. There was also a control group. In vitro diaphragm force, myofibril ultrastructure, αII-spectrin proteins, insulin-like growth factor-1 (IGF-1), and muscle atrophy F-box (MAF-box) mRNA were measured. Maximal tetanic tension (P(o)) decreased significantly with CMV. Combined MP plus CMV did not decrease P(o) further. With AMV, P(o) was similar to SB and controls. Combined MP plus AMV or MP plus SB decreased P(o) substantially. Combined MP plus CMV, MP plus AMV, or MP plus SB induced myofibrillar disruption that correlated with the reduced P(o). αII-spectrin increased, IGF-1 decreased, and MAF-box mRNA increased in both the CMV group and MP plus CMV group. Short-term, high-dose MP had no additive effects on CMV-induced diaphragm dysfunction. Combined MP plus AMV impaired diaphragm function, but AMV alone did not. We found that acute, high-dose MP produces diaphragm dysfunction depending on the mode of mechanical ventilation.

Drug combination therapies are common practice in the treatment of cancer. Cisplatin is the most active chemotherapeutic agent for lung cancer treatment. Osthole is a natural compound extracted from a number of medicinal plants. To determine whether osthole enhances the anticancer effect of cisplatin in human lung cancer, we treated NCI-H460 cells with osthole alone or in combination with cisplatin and evaluated cell growth and apoptosis using 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and fluorescence microscopy. The results showed that, in comparison with single agent treatment, the combination of osthole and cisplatin resulted in greater efficacy in growth inhibition and apoptosis induction. Western blot analysis revealed that the combination effect of osthole and cisplatin was due to regulation of the Bcl-2 family proteins. Findings of this investigation suggested that osthole combined with cisplatin is a potential clinical chemotherapeutic approach in human lung cancer.

a b s t r a c tTo demonstrate the interaction of calpastatin (CS) domain L (CS L ) with Cav1.2 channel, we investigated the binding of CS L with various C-terminus-derived peptides at % free, 100 nM, 10 lM, and

Background Acute pulmonary embolism (PE) is one of the leading causes of maternal mortality, and cesarean section is an established independent risk factor for PE. The diagnostic utility of D-dimer for PE in non-pregnant women has been well-established, but its role in women with suspected PE after cesarean section is unclear. Furthermore, the optimal threshold level in this patient population is unknown. Traditional D-dimer levels have low diagnostic specificity, resulting in many pregnant women being exposed to potentially harmful radiation despite negative diagnostic imaging results. This research aimed to optimize the clinical threshold for D-dimer to improve specificity while ensuring high sensitivity and to identify risk factors for PE after cesarean section. Methods This retrospective study of 289 women who underwent diagnostic imaging (ventilation/perfusion [V/Q] or computed tomographic pulmonary angiography [CTPA]) for suspected acute PE after cesarean delivery from 2010 to 2021 was conducted. Clinical data and laboratory indicators within 24 h postpartum including D-dimer levels were collected for analyses. Results The final analysis included 125 patients, among whom 33 were diagnosed with acute PE (incidence of 11.42%, 95% confidence interval 7.7–15.1). The receiver operating characteristic curve analysis suggested that a D-dimer cut-off value of 800 ng/mL had specificity of 25.26% and sensitivity of 100% for detecting PE. The cut-off value was adjusted to 1000 ng/mL with a specificity of 34.74% and a sensitivity of 96.67%. Using a D-dimer cut-off value of 800 ng/mL (instead of the conventional value of 500 ng/mL) increased the number of patients excluded from suspected PE from 9.6 to 18.4% without additional false-negative results. Of note, a history of known thrombophilia was significantly more common in patients with PE than in those without (P < 0.05). No other independent risk factors were noted in our study. Conclusions The D-dimer cut-off value of 800 ng/mL ensures high sensitivity and increases specificity compared to the conventional threshold of 500 ng/mL. Utilizing this higher threshold can reduce the number of unnecessary CT and subsequently unnecessary radiation exposure, in women after cesarean delivery. Prospective studies should also be conducted to verify these results.

New Findings r What is the central question of this study?Higher levels of positive end-expiratory pressure (PEEP) have recently been used in patients with acute respiratory distress syndrome (ARDS). In normal physiological conditions, the ability of the diaphragm to generate pressure is reduced when the lung volume is elevated beyond its functional residual capacity. It is unknown whether higher levels of PEEP will have a negative impact on diaphragmatic contraction in the presence of the pathophysiology of ARDS. r What is the main finding and its importance?Mechanical ventilation with higher levels of PEEP reduced lung injury, improved diaphragmatic contractility and increased the expression of both dihydropyridine receptor and ryanodine receptor in the diaphragms of rats with ARDS.Higher levels of positive end-expiratory pressure (PEEP) have recently been used in patients with acute respiratory distress syndrome (ARDS). In normal physiological conditions, the ability of the diaphragm to generate pressure is reduced when the lung volume is elevated beyond its functional residual capacity. Thus, it is critical to understand whether higher levels of PEEP will have a negative impact on diaphragmatic contraction in the presence of the pathophysiology of ARDS. This study was designed to determine whether higher levels of PEEP reduce diaphragmatic contractility in a rat model of ARDS generated using i.p. lipopolysaccharide. Forty rats were randomly assigned to the following five groups: a control group with no special treatment; an ARDS group with no mechanical ventilation; and three ARDS groups with mechanical ventilation with PEEP at 0, 5 or 10 cmH 2 O, respectively. We found that mechanical ventilation with PEEP reduced lung injury, improved diaphragmatic contractility and increased the expression of both dihydropyridine receptor and ryanodine receptor in the diaphragms of rats with ARDS. These changes were most significant at a PEEP of 10 cmH 2 O among all applied levels of PEEP. In conclusion, using a rat ARDS model, this study confirmed that diaphragmatic contractility was preserved by mechanical ventilation with high levels of PEEP.