[Study of protective effect and mechanism of vitamin C in lipopolysaccharide-induced septic renal injury].

OBJECTIVE: To explore the protective effect and its mechanism of vitamin C on septic renal injury induced by lipopolysaccharide (LPS). METHODS: Renal tubular epithelial cells HK-2 were induced with 10 mg/L LPS for 8 hours and 12 hours, respectively, and then 0.5 mmol/L and 1 mmol/L vitamin C were added, respectively. Cell viability was measured using cell proliferation and toxicity assay cell counting kit-8 (CCK-8) to determine suitable condition for subsequent experiments. HK-2 cells were divided into control group, LPS group and LPS+vitamin C group (LPS+VC group). The contents of necrosis factors phosphorylated mixed lineage kinase domain-like protein (p-MLKL) and phosphorylated receptor-interacting protein kinase 3 (p-RIPK3) were measured by Western blotting. The contents of inflammatory factors interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were determined by enzyme linked immunosorbent assay (ELISA) in each group. Differences among the groups were compared. RESULTS: CCK-8 showed that 1 mmol/L vitamin C improved the survival rate of HK-2 cells to 86% after 12 hours of LPS induction, so this condition was selected for subsequent experiments. After 12 hours LPS induction in HK-2 cells, the expressions of p-MLKL and p-RIPK3 were significantly higher than those of the control group, and the levels of IL-1ß and TNF-α were also significantly higher than those of the control group [IL-1ß (ng/L): 23.2±1.4 vs. 12.8±3.9, TNF-α (ng/L): 36.4±3.9 vs. 11.6±1.8, both P < 0.05], indicating the co-existence of cell necrosis and inflammation. Compared with LPS group, 1 mmol/L vitamin C significantly decreased the protein expression of p-MLKL and p-RIPK3, and also significantly decreased the levels of IL-1ß and TNF-α [IL-1ß (ng/L): 19.8±0.7 vs. 23.2±1.4, TNF-α (ng/L): 17.4±5.8 vs. 36.4±3.9, both P < 0.05]. CONCLUSIONS: Vitamin C can alleviate LPS-induced HK-2 cell damage, and reduce the expressions of necrotic factors and inflammatory factors.

Development of endotracheal intubation devices for patients with tumors.

The incidence and mortality of malignant tumors are rapidly increasing in the world. Patients with malignant tumors often need surgery for treatment. Endotracheal intubation is a necessary technique for surgical patients undergoing general anesthesia. It is also an important procedure for critically ill patients in the emergency room or ICU. Most patients with head and neck tumors and some specific patients have difficult airways, so the operator may need to use a variety of intubation devices. The commonly used devices for endotracheal intubation include endotracheal tube, direct laryngoscope, video laryngoscope, introducer, optical stylet, fiberoptic bronchoscope. With the advancement in science and technology, the endotracheal intubation devices have been improved, and new devices have been developed. These devices are safer and more feasible in clinical practice. In this review, we summarized the features and applications of some of the currently used devices. Each device has its own uniqueness and meets different needs. The devices and their respective properties are strongly suggested to be mastered by the anesthesiologists as well as related staffs, so as to select the appropriate device for intubation.

Application of "twelve-step" approach based on SEEKflex for difficult awake tracheal intubation in patients with cervical spinal tumor.

Difficult airway always occurs in patients with cervical spinal tumor. Awake tracheal intubation (ATI) is usually a primary safe approach for clinical doctors in these intractable difficult airways. It is of great significance to establish specific strategies to reduce related acute airway accidents. A novel "twelve-step" approach of awake tracheal intubation based on an improved introducer (Safe Easy Endotracheal Kit-flexible, "SEEKflex") was developed and practiced in model successfully. Patients with cervical spinal tumor in a single tertiary hospital were chosen to secure airway with this approach. Primary outcomes were safety and feasibility, defined as completion of ATI without serious adverse events, Secondary outcome was the first intubation attempt rate, total intubation time, satisfaction of patients in the whole process and relevant complications. We performed awake tracheal intubation with this approach to solve the difficult airway in five patients with cervical spinal tumor. The courses went successfully in all patients without any relevant complications. This novel "twelve-step" approach based on SEEKflex for ATI can be considered as one of optional safe choices for difficult airway in patients with cervical spinal tumor.

Vitamin C reduces vancomycin-related nephrotoxicity through the inhibition of oxidative stress, apoptosis, and inflammation in mice.

BACKGROUND: Vancomycin (VCM) is an antibiotic widely used to treat a range of serious bacterial infections; however, it is associated with nephrotoxicity. Vitamin C (VC) is a classical antioxidant that can alleviate various organ injuries and inflammatory responses by reducing inflammation and oxidative stress. This study aimed to examine the effect of VC on VCM-related nephrotoxicity in mice. METHODS: Mice were randomized into four groups: control, VCM (400 mg/kg/day), VCM (400 mg/kg/day) + VC (200 mg/kg/day), and VC (200 mg/kg/day) groups. Both VCM and VC were administered via intraperitoneal injection for 7 d, after which kidney and blood samples were collected and evaluated. Creatinine (Cr), blood urea nitrogen (BUN), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and nuclear factor-κB (NF-κB) were measured. RESULTS: In the VCM group, kidney index, renal injury score, cell apoptosis, serum Cr and BUN, and kidney Cr, BUN, MDA, IL-1ß, IL-6, TNF-α, and NF-κB were higher compared to the control group (all P<0.05), while body weight and kidney SOD activity were lower (both P<0.05). By contrast, no differences were observed between the control and VC groups (VC and VCM + VC groups) for all these indicators. CONCLUSIONS: The antioxidant VC reduces VCM-related renal injury by reducing oxidative stress, cell apoptosis, and inflammation.

Aqueous extract of Rabdosia rubescens leaves: forming nanoparticles, targeting P-selectin, and inhibiting thrombosis.

The hot water extract of Rabdosia rubescens was traditionally used as an antithrombotic medicine. To explore its antithrombotic utility and mechanism, we carried out a series of in vitro and in vivo assays in this study. In vitro platelet aggregation assay showed that the half maximal inhibitory concentration values of aqueous extract of R. rubescens leaves (AERL) inhibiting platelet aggregation induced by thrombin, arachidonic acid, adenosine diphosphate, and platelet-activating factor ranged from 0.12 mg/mL to 1.43 mg/mL. The minimal effective oral dose of AERL inhibiting the rats from forming thrombus was 25 mg/kg. Both in vitro and in vivo actions were correlated with AERL concentration-dependently inhibiting sP-selectin release. In water, AERL formed nanoparticles, and their size depended on the concentration. Docking the five nucleotides, 21 phenolic acids, and four diterpenoids identified by high-performance liquid chromatography-photodiode array detector/(-)electrospray ionization-tandem mass spectrometry analysis into the active site of P-selectin, rosmarinic acid was predicted to be the antithrombotic ingredient of AERL. In flow cytometry analysis, 1 µM of rosmarinic acid effectively inhibited sP-selectin release in arachidonic acid-activated platelets. In a rat model, 5 mg/kg of oral rosmarinic acid effectively inhibited thrombosis.

Effects of sevoflurane and propofol on right ventricular function and pulmonary circulation in patients undergone esophagectomy.

OBJECT: Sevoflurane and propofol are both widely used in clinical anesthesia. The aim of this study is to compare the effects of sevoflurane and propofol on right ventricular function and pulmonary circulation in patients receiving esophagectomy. METHODS: Forty adult patients undergoing an elective open-chest thoracotomy for esophagectomy were randomized to receive either propofol (n=20) or sevoflurane (n=20) as the main anesthetic agent. The study was performed in Changzheng Hospital. Hemodynamic data were recorded at specific intervals: before the surgery (T0), BIS values reaching 40 after anesthesia induction (T1), two-lung ventilation (T2), ten minutes after one-lung ventilation (T3), the end of the operation (T4) using PiCCO2 and Swan-Ganz catheter. RESULTS: CI, RVEF, RVSWI and RVEDVI were significantly smaller in propofol group than those in sevoflurane group throughout the surgery (P<0.05). However, SVRI was significantly greater in propofol group than that in sevoflurane group (P<0.05). Compared with the patients in propofol group, the patients who received sevoflurane had a greater reduction in OI and increase in Os/Ot (P<0.05). And, PVRI was significantly smaller in sevoflurane group than in propofol group (P<0.05). CONCLUSION: Anesthesia with sevoflurane preserved better right ventricular function than propofol in patients receiving esophagectomy. However, propofol improved oxygenation and shunt fraction during one-lung ventilation compared with sevoflurane anesthesia. To have the best effect, anesthesiologists can choose the two anesthetics flexibly according to the monitoring results.

Folded Conformation, Cyclic Pentamer, Nano-Structure and PAD4 Binding Mode of YW3-56.

The physical and chemical mechanisms of small molecules with pharmacological activity forming nano-structures are developing into a new field of nano-medicine. By using ROESY 2D NMR spectroscopy, trandem mass spectroscopy, transmission electron microscopy and computer-assisted molecular modeling, this paper demonstrated the contribution of the folded conformation, the intra- and intermolecular π-π stacking, the intra- and intermolecular hydrogen bonds, and the receptor binding free energy of 6-dimethylaminonaph-2-yl-{N-S-[1-benzylcarba-moyl-4-(2-chloroacetamidobutyl)]-carboxamide (YW3-56) to the rapid formation of nano-rings and the slow formation of nano-capsules. Thus we have developed a strategy that makes it possible to elucidate the physical and chemical mechanisms of bioactive small molecules forming nano-structures.