[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.

Immunological mechanisms of scarring and their psychological impact on patients.

A scar is a local symptom, which results from severe physical, biological and chemical damage to human skin and soft tissue. Scars can affect both skin appearance and function. The affected skin or soft tissue cannot be completely repaired normally by itself and is replaced by formed fibrous tissue. Patients with scars can develop physical pain and mental conditions, especially those with scars left after burns, scalds and severe traumas. The scar proliferation phase can be up to several years which could be almost unbearable for patients. Also, the atrophic period afterwards makes the patient's face unrecognizable and dysfunctional, causing great physical and mental impairment. Therefore, scar repair is of great clinical importance for patients, and understanding the immunological mechanisms of scar repair is an important prerequisite for the effective treatment of scars. This study is a systematic review of current research advances about the immunological mechanisms of scar repair, so as to provide a reference for the selection of regimens in clinical treatment.

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.

Vitamin C attenuates vancomycin induced nephrotoxicity through the reduction of oxidative stress and inflammation in HK-2 cells.

BACKGROUND: Oxidative stress is one of the possible mechanisms in vancomycin (VCM) induced nephrotoxicity. Some studies suggested that high dose Vitamin C (VC) has protective effect against the nephrotoxicity in mice, but the underlying molecular mechanism is not mentioned. We investigated the potential targets of high dose VC against oxidative stress and inflammation induced by VCM in renal tubular epithelial cells. METHODS: We conducted an in vitro study using an immortalized proximal tubule epithelial cell line from a normal adult human kidney (HK-2). RESULTS: VCM added to HK-2 cells caused an increase of cell death, oxidative stress and expression of inflammatory cytokines. Co-treatment with 0.5 and 1 mM VC attenuated 4-8 mM VCM induced cell death and increased the cell viability to 58-90%. VC significantly decreased lipid peroxidation and increased superoxide dismutase activity. The upregulations of NF-κB, TNF-α and IL-6 in HK-2 cells under 4 mM VCM were also reversed by 0.5 mM VC through the inhibition of oxidative stress. CONCLUSIONS: This study showed for the first time that VC can attenuate the VCM induced nephrotoxicity by decreasing lipid peroxidation and expression of inflammatory cytokines, and increasing superoxide dismutase 2 (SOD2) activity, this effect may relate to the regulation of ROS/NF-κB pathway.

Reintubation during COVID-19 pandemic: a simple self-made guiding device facilitates reintubation and minimizes transmission.

Consensus guidelines to protect airway managers during COVID-19 were developed to encourage safe, accurate and swift performance in intubation and extubation, but reintubation was not considered. With the massive surge of patients requiring mechanical ventilation in this COVID-19 pandemic, great incidence of difficult airways may necessitate reintubation. Equipments could be used now in extubation and reintubation are either too expensive and time-consuming in decontamination, or have not gained wide acceptance. Here, we adapted an extubation device from an intubating stylet, which is provided as accessory of endotracheal tube. Such stylet could provide safe access for expediting reintubation both during and after the COVID-19 pandemic, which is inexpensive, single-use, readily available, straightforward to handle, and well-tolerated, thereby benefiting both the patients and healthcare providers.

Clinical characteristics and prediction analysis of the recovered COVID-19 patients with re-detectable positive RNA test.

BACKGROUND: Previous studies have unveiled the occurrence of re-detectable positive (RP) RNA test result after hospital discharge among recovered COVID-19 patients, but the clinical characteristics of RP patients (RP patients) and the potential features affecting RP RNA test outcome remain unclear. METHODS: A total of 742 COVID-19 patients discharged between March 1st, 2020 and March 20th, 2020 were enrolled. All patients were followed-up for SARS-CoV-2 RNA test and RP patents were identified. The clinical characteristics between RP patients and NRP patients were compared, and the potential features affecting re-detectable RNA test outcome were further evaluated. RESULTS: Up to April 9th, 2020, 60 recovered patients (8.09%) had been re-detected to be SARS-CoV-2 RNA positive. Among those 60 RP patients, the median RP time was 12 days from the last negative result of SARS-CoV-2 RNA test or 10 days from hospital discharge. RP patients were prone to be older, having mild/moderate conditions, unilateral lung involvement and fatigue, chills, stuffy or runny nose, with high lymphocyte count. Multivariate logistic analysis and COX regression analysis demonstrated that age, lymphocyte count, urea nitrogen, stuffy or runny nose as well as lung involvement were independently associated with RP RNA test (P<0.05). CONCLUSIONS: Older patients accompanied with stuffy or runny nose, low urea nitrogen as well as unilateral lung involvement were more likely to develop RP RNA test result after hospital discharge. Therefore, we strongly suggest using broncho-alveolar lavage fluid for RNA detection, extending quarantine time, and conducting continual follow-up medical examination for those discharged patients.

[High dose vitamin C significantly reduces the nephrotoxicity of vancomycin in critically ill patients].

OBJECTIVE: To observe the changes of renal function in critically ill patients using vancomycin and analyze the renal protective effect of high dose vitamin C (VC) on vancomycin nephrotoxicity. METHODS: Retrospective analysis was carried out to enroll the patients who were hospitalized in emergency intensive care unit (ICU) of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2012 to October 2019. All patients were administered with vancomycin or VC infusion in addition. According to the infusion of vancomycin alone or in combination with VC, the patients were divided into vancomycin group and vancomycin in combination with VC group; vancomycin group was further divided into two groups according to before vancomycin or after vancomycin usage; combination group were further divided into two groups according to before VC use or after VC. The initial dosage of vancomycin was calculated according to the actual weight of the patient and adjusted according to the renal function. The dosage of VC was determined according to the disease severity of the patient, and the dosage range was 50-200 mg×kg-1×d-1, continuously infused into the body. The age, gender, weight and renal function etc. were recorded and analyzed. RESULTS: A total of 245 patients who met the requirements were included in the analysis. There were 127 patients in the vancomycin group and 118 patients in the combination group. The causes of patients admitted to ICU were pulmonary infection, sepsis, severe acute pancreatitis, etc. Among them, pulmonary infection accounted for 63.0% in vancomycin group, while severe acute pancreatitis accounted for 61.9% in combination group. The quick sequential organ failure assessment (qSOFA) score of combination group was significantly higher than that of vancomycin group [1.0 (0, 1.0) vs. 0 (0, 0.2), P < 0.01], its basic renal function was also significantly worse [serum creatinine (SCr, µmol/L): 98.0 (65.0, 178.2) vs. 56.0 (42.2, 71.0), blood urea nitrogen (BUN, mmol/L): 11.30 (6.48, 18.38) vs. 4.70 (3.45, 8.10), both P < 0.05], and the average daily dose of vancomycin was also significantly lower than that of vancomycin group (mg×kg-1×d-1: 23.0±9.4 vs. 26.6±8.5, P < 0.01). Compared with vancomycin before administration, the renal function was getting worse significantly after vancomycin administration [SCr (µmol/L): 68.0 (50.2, 104.5) vs. 56.0 (42.2, 71.0), BUN (mmol/L): 5.35 (3.75, 9.83) vs. 4.70 (3.45, 8.10), both P < 0.05]. Combination with VC significantly improved renal function compared with that before VC treatment [SCr (µmol/L): 79.0 (58.0, 129.0) vs. 98.0 (65.0, 178.2), P < 0.05; BUN (mmol/L): 9.60 (6.10, 18.30) vs. 11.30 (6.48, 18.38), P > 0.05] and shortened the length of ICU stay [days: 28.5 (14.8, 54.2) vs. 37.0 (25.0, 55.0), P < 0.01]. CONCLUSIONS: The incidence of drug-induced renal injury caused by vancomycin is high. Intravenous high dose VC can significantly reduce the nephrotoxicity of vancomycin and shorten the length of hospital stay. When vancomycin is used in critically ill patients, VC can be used in combination to reduce or avoid drug-induced renal injury, improve curative effect and reduce toxic effects.

[PK/PD of vancomycin in patients with severe acute pancreatitis combined with augmented renal clearance].

OBJECTIVE: To evaluate the serum trough concentration and the pharmacokinetics/pharmacodynamics (PK/PD) of vancomycin in patients with severe acute pancreatitis (SAP), and analyze the effect of vancomycin continuous infusion for optimizing the characteristics of its PK/PD. METHODS: The inhospital patients with SAP received vancomycin treatment and admitted to emergency intensive care unit (EICU) of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2011 to December 2016 were enrolled. Steady-state trough concentrations of vancomycin from patients were collected retrospectively. The SAP patients were divided into augmented renal clearance (ARC) and non-ARC groups, as well as systemic inflammatory response syndrome (SIRS) and non-SIRS groups according to the patients with or without symptom above. Adjustments of increased dosage or 24-hour continuous infusion or increase vancomycin dose were made for patients if the steady-state trough concentrations fell below the target level. Steady state trough concentration for vancomycin intermittent infusion or steady state concentration for vancomycin continuous infusion was determined by the fluorescence polarization immunoassay method. PK parameters of vancomycin were calculated using the Bayesian estimator and the area under the serum drug concentration-time curve (AUCc-t), the minimum inhibitory concentration (MIC) and AUCc-t/MIC was recorded and calculated. RESULTS: The steady state trough concentration or steady state concentration from 61 patients with SAP were collected with mean steady state trough concentration of vancomycin of (7.7±4.4) mg/L, which was significantly lower than standard concentration (15 mg/L, P < 0.001). Apparent volume of distribution (Vd) and clearance of vancomycin was (1.06±0.26) L/kg and (8.9±2.8) L/h. The serum steady state trough concentration of vancomycin in ARC group (n = 33) was significantly lower than that in non-ARC group (n = 28; mg/L: 6.7±3.5 vs. 8.2±4.1, P < 0.01), clearance was significantly increased (L/h: 9.8±2.9 vs. 7.7±2.2, P < 0.01). Compared with non-SIRS group (n = 31), the serum steady state trough concentration of vancomycin in SIRS group (n = 30) was significantly lowered (mg/L: 6.1±3.2 vs. 13.0±4.2, P < 0.01), and clearance was significantly increased (L/h: 9.4±2.0 vs. 7.1±2.1, P < 0.05). Compared with the only increasing vancomycin dose group (n = 29), vancomycin continuous infusion for 24 hours (n = 21) could significantly reduce daily dosage (mg/kg: 13.6±3.9 vs. 19.1±3.5, P < 0.01), increase the serum trough concentration (mg/L: 18.1±7.0 vs. 12.6±5.3, P < 0.01), and improve the AUCc-t/MIC. CONCLUSIONS: The serum trough concentration of vancomycin was significantly reduced in SAP patients with ARC. The more serious of the SIRS is, the lower the vancomycin trough concentration is. Vancomycin 24-hour continuous infusion could optimize the PK/PD parameters, decrease the daily dose, increase the clinical effect, and reduce the bacterial resistance.

Activation of Endocannabinoid Receptor 2 as a Mechanism of Propofol Pretreatment-Induced Cardioprotection against Ischemia-Reperfusion Injury in Rats.

Propofol pretreatment before reperfusion, or propofol conditioning, has been shown to be cardioprotective, while its mechanism is unclear. The current study investigated the roles of endocannabinoid signaling in propofol cardioprotection in an in vivo model of myocardial ischemia/reperfusion (I/R) injury and in in vitro primary cardiomyocyte hypoxia/reoxygenation (H/R) injury. The results showed that propofol conditioning increased both serum and cell culture media concentrations of endocannabinoids including anandamide (AEA) and 2-arachidonoylglycerol (2-AG) detected by LC-MS/MS. The reductions of myocardial infarct size in vivo and cardiomyocyte apoptosis and death in vitro were accompanied with attenuations of oxidative injuries manifested as decreased reactive oxygen species (ROS), malonaldehyde (MDA), and MPO (myeloperoxidase) and increased superoxide dismutase (SOD) production. These effects were mimicked by either URB597, a selective endocannabinoids degradation inhibitor, or VDM11, a selective endocannabinoids reuptake inhibitor. In vivo study further validated that the cardioprotective and antioxidative effects of propofol were reversed by selective CB2 receptor antagonist AM630 but not CB1 receptor antagonist AM251. We concluded that enhancing endogenous endocannabinoid release and subsequent activation of CB2 receptor signaling represent a major mechanism whereby propofol conditioning confers antioxidative and cardioprotective effects against myocardial I/R injury.

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.