An engineered nanoplatform cascade to relieve extracellular acidity and enhance resistance-free chemotherapy.

Tumor extracellular acidity and chemoresistance are regarded as the main obstacles to achieving optimal chemotherapeutic efficacy in tumor therapy. Herein, a new kind of acid-cascade P-S-Z nanoparticles (NPs) is developed to relieve extracellular acidosis and enhance chemotherapy without causing drug resistance. The P-S-Z NPs selectively accumulate in tumors and then regulate the release of S-Z NPs containing syrosingopine (Syr) and acid-activated prodrug ZMC1-Pt depending on the extracellular acidity. Benefiting from their small size and positive surface charge, S-Z NPs are easily internalized by tumor cells in deep tumor tissue, facilitating the release of Syr to inhibit lactic acid excretion and ultimately enhance cell acidosis. The prolonged intracellular acidosis not only inhibits tumor cell proliferation, but also continuously triggers the activation of ZMC1-Pt prodrug, a platinum-based chemotherapeutic drug that effectively eliminates cancer cells and restores wild-type p53 function to prevent tumor chemoresistance. As a proof of concept, this is a promising strategy to transfer the adverse effect of intracellular acidosis to facilitate chemotherapy. This well-designed delivery system effectively kills tumor cells without causing significant tumor drug resistance, thus opening a new window to treat cancer.

A risk score for early predicting bloodstream infections in febrile obstetric patients: a pilot study.

PURPOSE: Early prediction of bloodstream infections (BSI) among obstetric patients remains to be a challenge for clinicians. The objective of this study was to develop a risk score and assess its discriminative ability in febrile obstetric patients in a maternal intensive care unit (ICU). METHODS: Between May 2015 and August 2020, a total of 497 febrile obstetric patients were categorized into BSI group (n = 276) and Non-BSI group (n = 221) based on the result of blood cultures. White blood cell count, C-reactive protein (CRP), procalcitonin (PCT), time of interval from amniorrhea to fever (IFAF) and maximum body temperature (Tmax) were compared between the two groups. All patients were divided into training set (n = 298) and validation set (n = 199). The risk score was established using univariate and multivariate logistic regression from patients in the training set, and its discriminative ability was tested among patients in the validation set. RESULTS: The levels of neutrophil, CRP, PCT, IFAF and Tmax were significantly higher in BSI group than those in Non-BSI group. PROM, Tmax, neutrophil and CRP acted as independent predictive factors for BSI in the training set. The area under the receiver operating characteristic curve of risk score for early prediction of BSI in the training, validation set and the whole population was 0.829 (95% CI 0.783-0.876), 0.848 (95% CI 0.792-0.903) and 0.838 (95% CI 0.803-0.873), respectively. CONCLUSION: The risk score has a feasible discriminatory ability in early prediction of BSI in febrile obstetric patients.

A Quantitative Study of the Dimensional Change of Inferior Vena Cava on Computed Tomography During Acute Hemorrhage Shock in Swine.

Background: The purpose of this study was to examine the dimensional change of IVC during acute hemorrhage through a volume-controlled acute hemorrhagic shock model in swine. Methods: Volume-controlled hemorrhage was performed in 10 adult Bama mini pigs. Enhanced CT scan and hemodynamic monitoring were performed when the cumulative blood loss volume reached 0%, 10%, 20%, 30%, and 40%. The transverse diameter (T) and anteroposterior diameter (AP) of IVC were measured in axial images. Hemodynamic parameters were obtained with Pulse Contour Cardiac Output (PiCCO) hemodynamic monitor device. Arterial blood samples were also collected for artery blood gas analysis at each time point. Results: As the blood loss volume increased, the collapsibility (T/AP) and cross section area (CSA) of IVC significantly changed first in hepatic level and pre-renal level. The significant decrease of the CSA of IVC (shrink) occurred early when the blood loss volume reached only 10%, but the collapse of IVC occurred until the blood loss volume reached 30%. Conclusions: IVC shrank early but collapsed late during the acute hemorrhage in swine. The finding of collapsed IVC on CT scans suggested severe hypovolemic shock. Evaluation of the IVC at the CT scans can be an adjunctive test of the hemodynamic status in trauma patients.

A Durable Nickel Single-Atom Catalyst for Hydrogenation Reactions and Cellulose Valorization under Harsh Conditions.

Hydrothermally stable, acid-resistant nickel catalysts are highly desired in hydrogenation reactions, but such a catalyst remains absent owing to the inherent vulnerability of nickel under acidic conditions. An ultra-durable Ni-N-C single-atom catalyst (SAC) has now been developed that possesses a remarkable Ni content (7.5 wt %) required for practical usage. This SAC shows not only high activities for hydrogenation of various unsaturated substrates but also unprecedented durability for the one-pot conversion of cellulose under very harsh conditions (245 °C, 60 bar H2 , presence of tungstic acid in hot water). Using integrated spectroscopy characterization and computational modeling, the active site structure is identified as (Ni-N4)⋅⋅⋅N, where significantly distorted octahedral coordination and pyridinic N constitute a frustrated Lewis pair for the heterolytic dissociation of dihydrogen, and the robust covalent chemical bonding between Ni and N atoms accounts for its ultrastability.

Effect of retension sutures on abdominal pressure after abdominal surgery.

PURPOSE: To evaluate the effect of retention sutures on abdominal pressure and postoperative prognosis in abdominal surgery patients. METHODS: This prospective cohort study included patients who were admitted to Daping Hospital from May 15, 2014 to October 11, 2014. A total of 57 patients were enrolled, including 18 patients in the "U" type retention suture group, 17 patients in the intermittent retention suture group, and 22 patients in non-retention suture group. The demographic data, clinical data and risk factors for abdominal wound dehiscence were recorded. The bladder pressure (IVP) was monitored preoperatively, intraoperatively, and four days postoperatively. Additionally, the incidence of abdominal wound dehiscence and infection 14 days after the operation was recorded. RESULTS: During the operation, the IVP decreased and then increased; it was at its lowest 1 h after the start of the operation (5.3 mmHg ± 3.2 mmHg) and peaked after tension-reducing (8.8 mmHg ± 4.0 mmHg). The IVP values in the "U" type retention suture group and intermittent retention suture group were higher than in the non-retention suture group 4 days after operation (p < 0.005). The Visual Analogue Scale (VAS) pain scores were 3.9 ± 2.2, 3.8 ± 2.0, and 3.0 ± 1.0 in the retention suture group, intermittent retention suture group and non-retention suture group, respectively. The VAS pain scores in the "U" type tension-reducing group and intermittent tension-reducing group were higher than in the non-tension-reducing group (p < 0.005). CONCLUSION: Although retention sutures may reduce the incidence of postoperative wound dehiscence in abdominal surgery patients, they can increase the IVP and postoperative pain.

[Effect of insulin-like growth factor-1 on hyperoxia-induced apoptosis in A549 cells].

OBJECTIVE: To investigate the effect of insulin-like growth factor-1 (IGF-1), which can promote cell differentiation and inhibit cell apoptosis, on hyperoxia-induced apoptosis in A549 cells and its anti-apoptotic mechanism. METHODS: A549 cells were sub-cultured, exposed to hyperoxic conditions and were then treated with different concentrations of IGF-1 (1, 10, and 100 ng/mL) for 48 hours. Cell viability was measured by MTT assay. Cell apoptosis was evaluated by Annexin V-FITC/PI double-staining flow cytometry. Expression levels of Bax and Bcl-2 were measured by flow cytometry. RESULTS: The middle-dose and high-dose IGF-1 intervention groups had higher cell viabilities than the hyperoxic exposure group [(64±3)% and (88±4)% vs (51±3)%; P<0.05]. Compared with the air control group, the hyperoxic exposure group had a significantly higher apoptotic rate [(38.3±5.4)% vs (2.4±0.9)%; P<0.05], a significantly lower expression level of Bcl-2 [(72±5)% vs (91±4)%; P<0.05], and a significantly higher expression level of Bax [(54±6)% vs (3±2)%; P<0.05]. Compared with the hyperoxic exposure group, the low-dose, middle-dose, and high-dose IGF-1 intervention groups had significantly lower apoptotic rates [(16.1±4.7)%, (9.2±2.8)%, and (6.9±2.5)% vs (38.3±5.4)%; P<0.05], significantly higher expression level of Bcl-2 [(79±4)%, (94±4)%, and (100±5)% vs (72±5)%; P<0.05], and significantly lower expression level of Bax [(26±4)%, （5±2)%, and (4±2)% vs (54±6)%; P<0.05]. CONCLUSIONS: Hyperoxia significantly inhibits proliferation and promotes apoptosis in A549 cells. IGF-1 may promote cell proliferation and inhibit hyperoxia-induced apoptosis in A549 cells by regulating the expression of Bcl-2 and Bax.