In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO2-induced cardiac injury using a mouse model. Methods Male C57BL/6 mice were intratracheally instilled with SiO2 to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed. Results SiO2 altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO2-induced mitochondrial damage and myocardial injury.SiO2 inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion Iron overload-induced ferroptosis contributes to SiO2-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO2 cardiotoxicity,potentially via modulation of the Nrf2 pathway.

The use of nitrification inhibitors has been suggested as a strategy to decrease cadmium(Cd)accumulation in crops.However,the most efficient nitrification inhibitor for mitigating crop Cd accumulation remains to be elucidated,and whether and how changes in soil microbial structure are involved in this process also remains unclear.To address these questions,this study applied three commercial nitrification inhibitors,namely,dicyandiamide(DCD),3,4-dimethylpyrazole phosphate(DMPP),and nitrapyrin(NP),to pakchoi.The results showed that both DCD and DMPP(but not NP)could efficiently decrease Cd concentrations in pakchoi in urea-and ammonium-fertilized soils.In addition,among the three tested nitrification inhibitors,DMPP was the most efficient in decreasing the Cd concentration in pakchoi.The nitrification inhibitors decreased pakchoi Cd concentrations by suppressing acidification-induced Cd availability and reshaping the soil microbial structure;the most effective nitrification inhibitor was DMPP.Ammonia oxidation generates the most protons during nitrification and is inhibited by nitrification inhibitors.Changes in environmental factors and predatory bacterial abundance caused by the nitrification inhibitors changed the soil microbial structure and increased the potential participants in plant Cd accumulation.In summary,our study identified DMPP as the most efficient nitrification inhibitor for mitigating crop Cd contamination and observed that the soil microbial structural changes caused by the nitrification inhibitors contributed to decreasing Cd concentration in pakchoi.

Purpose: Nonalcoholic fatty liver disease (NAFLD) is closely associated with metabolic diseases, including obesity and diabetes, and has gradually become the most common cause of chronic liver disease. We investigated the effects of sodium glucose cotransporter 2 (SGLT2) inhibitor canagliflozin on NAFLD in high-fat diet (HFD)-induced obese mice and possible underlying mechanisms. Materials and Methods: Male C57BL/6 mice were fed a normal-diet, HFD, or HFD with canagliflozin for 14 weeks. AML-12 hepatocytes were treated with canagliflozin. Expression of related pathways was assessed. Results: Canagliflozin administration reduced body weight and fat mass, compared with HFD alone. Canagliflozin improved glucose and lipid metabolic disorders. Compared with HFD-fed mice, liver weight, serum alanine transaminase (ALT) levels, and hepatic lipid accumulation were decreased after canagliflozin administration. Additionally, canagliflozin upregulated lipolysis markers (CPT1a, ACOX1, and ACADM), downregulated lipogenesis markers (SREBP-1c and FASN), and suppressed the production of inflammatory cytokines (TNFα, MCP1, IL-1β, and IL-6), consistent with significantly increased LC3 II/I and Atg7 levels in the liver following canagliflozin treatment. In vitro, canagliflozin increased CPT1a, ACOX1, and ACADM expression, decreased SREBP-1c and FASN protein expression, and reduced TNFα, MCP1, IL-1β, and IL-6 mRNA levels in lipid mixture (LM)-induced hepatocytes in a dose-dependent manner. These changes were reversed by 3-MA, an autophagy inhibitor. Conclusion Our findings suggest that canagliflozin ameliorates the pathogenesis of NAFLD by regulating lipid metabolism and inhibiting inflammation, which may be associated with its promotion of autophagy.

Objective    To compare the clinical effects of segmentectomy and lobectomy for ≤2 cm lung adenocarcinoma with micropapillary and solid subtype negative by intraoperative frozen sections. Methods    The patients with adenocarcinoma who received segmentectomy or lobectomy in multicenter from June 2020 to March 2021 were included. They were divided into two groups according to a random number table, including a segmentectomy group (n=119, 44 males and 75 females with an average age of 56.6±8.9 years) and a lobectomy group (n=115, 43 males and 72 females with an average of 56.2±9.5 years). The clinical data of the patients were analyzed. Results    There was no significant difference in the baseline data between the two groups (P>0.05). No perioperative death was found. There was no statistical difference in the operation time (111.2±30.0 min vs. 107.3±34.3 min), blood loss (54.2±83.5 mL vs. 40.0±16.4 mL), drainage duration (2.8±0.6 d vs. 2.6±0.6 d), hospital stay time (3.9±2.3 d vs. 3.7±1.1 d) or pathology staging (P>0.05) between the two groups. The postoperative pulmonary function analysis revealed that the mean decreased values of forced vital capacity and forced expiratory volume in one second percent predicted in the segmentectomy group were significantly better than those in the lobectomy group (0.2±0.3 L vs. 0.4±0.3 L, P=0.005; 0.3%±8.1% vs. 2.9%±7.4%, P=0.041). Conclusion    Segmentectomy is effective in protecting lungs function, which is expected to improve life quality of patients.

Objective:To identify age and gender standardized body mass index among children and adolescents and explore their associations with high blood pressure (HBP) in late adolescence.Methods:The current study was based on the Health Promotion Program for Children and Adolescents, school-based surveillance successively conducted from 2012 to 2019 in Suzhou, China. A total of 11 812 children and adolescents aged 16-18 years, who had ≥4 examination records during 2012-2018 and were also involved in a surveillance program in 2019, were included. Latent class growth mixture modeling was used to identify the BMI-Z trajectories in different genders, and multivariate logistic regression was used to analyze the associations between different BMI-Z trajectories and risk of HBP in late adolescence.Results:Six distinct BMI-Z trajectories were determined for both genders:thin, slightly thin,standard, declining, overweight, and obese. Compared with the regular group, the obesity group had 94.0% ( OR=1.94, 95% CI: 1.43-2.63) and 107.0% ( OR=2.07, 95% CI: 1.33-3.22) increased risk of developing HBP in late adolescence in boys and girls, respectively. However, a neutral association was found between the descending group and HBP in late adolescence. Conclusions:Persistent obesity in children may increase the risk of HBP in their late adolescence. If an obese child restores normal weight before late adolescence, the risk of HBP may reduce.

Glypican-3 (GPC3) is a key member of Glypican family and plays an important role in the development, angiogenesis and metastasis of hepatocellular carcinoma (HCC). Most HCC overexpresses GPC3, but GPC3 is hardly detected in normal adult liver and benign liver lesions, so it is regarded as a highly specific diagnostic marker and an ideal therapeutic target for HCC. In this study, we cloned the heavy and light chain variable region gene from the monoclonal antibody targeted to GPC3 screened in the previous stage, and linked it with a segment of flexible peptide (Linker) to obtain the single chain antibody against GPC3. The single chain antibody gene was cloned into vector for prokaryotic expression and purified to obtain high purity protein. Detection shows that the single-chain antibody produced by us has the same binding activity with the full-length antibody, and can accurately target the tumor site of Huh7 tumor-bearing model mice after coupling Cy5.5 fluorescence, suggesting that the single-chain antibody has the potential to realize multi-directional liver cancer precise surgical navigation under the guidance of a probe.
Animals ; Antibodies, Monoclonal ; Carcinoma, Hepatocellular/genetics* ; Glypicans/genetics* ; Liver Neoplasms/diagnosis* ; Mice

Background: This study aims to investigate the effect of integrin β1 on wound healing induced by adipose-derived stem cells (ADSCs), as well as the corresponding mechanism. Methods: Integrin β1 was overexpressed in ADSCs. Thereafter, flow cytometry and transwell chambers technology were used to measure the endothelial-like differentiation (CD31 as a biomarker of endothelial cell) and cell migration, respectively. Western blot was used to detect the activation of PI3K/AKT, NF-κB and ERK signaling pathways. The effects of integrin β1 overexpression on healing time, healing rate and fibroblast number were further evaluated in the rat models of chronic refractory wound. Results: The overexpression of integrin β1 increased CD31+ endothelial-like cells (about 3.6-fold), promoted cell migration (about 1.9-fold) and enhanced the activation of PI3K (p-PI3K; about 2.1-fold) and AKT (p-AKT; about 2.2-fold). These effects were all weakened when PI3K/AKT pathway was inhibited by LY294002 treatment. In addition, the experiments in rat wound models showed that integrin β1 overexpression obviously shortened healing time (approximately 0.41-fold), increased healing rate (about 2.7-fold, 2.8-fold and 1.6-fold at day 7, 14 and 21) and increased the number of fibroblasts (approximately 3.1-fold at day 21). All of the above differences were statistically significant (p < 0.05). Conclusion Integrin β1 can promote the migration and endothelial-like differentiation of ADSCs by activating PI3K/AKT pathway and then enhance the function of ADSCs in promoting wound healing.

Objective:The blood free carnitine levels of preterm infants with neonatal respiratory distress syndrome (NRDS) were detected within 7 days after birth, and the correlation between blood free carnitine levels and NRDS in preterm infants was explored.Methods:Seventy premature infants with gestational ages from 28 to 36 weeks who were admitted to the NICU of the Affiliated Hospital of Inner Mongolia Medical University from January 1, 2017 to December 31, 2019 were selected as the participants.Among them, 35 cases were in the NRDS group, while 35 cases of premature infants without NRDS were chosen as the control group.Heel blood samples were collected from all subjects within 6 hours, 3 days and 7 days after birth, and the levels of blood free carnitine were detected by tandem mass spectrometry.Results:Within 7 days after birth, the levels of free carnitine in blood of premature infants in the two groups gradually decreased with time, but the decreasing trend was not similar( F=4.096, P=0.021). Compared with 6 hours after birth, the blood free carnitine level in NRDS group decreased significantly with 3 days after birth[(35.24±9.58) μmol/L vs.(23.96±7.12) μmol/L, P<0.05]. The levels of blood free carnitine in NRDS group at 6 hours and 3 days after birth were significantly lower than those in control group[(35.24±9.58) μmol/L vs.(40.85±11.39) μmol/L; (23.96±7.12) μmol/L vs.(29.60±8.05) μmol/L, P<0.05]. There was no significant difference in blood free carnitine levels between the two groups at 7 days after birth ( P>0.05). Conclusion:The blood free carnitine levels of premature infants decreased within 7 days after birth.The decrease of carnitine level in premature infants with NRDS may be related to the occurrence and development of NRDS.

Objective: To investigate alterations of blood perfusion in subcortical regions in patients with Parkinson′s disease (PD) by three dimentional arterial spin labeling (ASL) magnetic resonance imaging (MRI). Methods: Thirty patients with PD and 40 control subjects were recruited from the inpatient and outpatient of the Department of Neurology of Northern Jiangsu People′s Hospital during October 2014 to October 2016, and routine brain MRI and 3D pseudo-continuous pulse ASL were performed on all the subjects. The cerebral blood flow (CBF) maps derived from 3D ASL were coregistered to the Montreal Neurological Institute brain space. The stereo-templates of bilateral caudate nucleus, putamen nucleus, globus pallidum and thalamus from Anatomical Automatic Labeling were used as region of interest (ROI) to exstract absolute CBF values in these subcortical regions, respectively. The CBF ratio (rCBF) values represented by individual whole brain CBF divided by each of the regional CBF were also calculated in consideration of the difference between individual whole brain CBF. The CBF and rCBF values were compared respectively between groups by one-way analysis of variance. Results: The subcortical CBF values (ml·100 g^-1·min^-1) for each ROI in PD (caudate nucleus (left: 35.32±6.47, right: 36.17±7.07), globus pallidum (left: 40.42±5.83, right: 40.18±5.70), putamen nucleus (left: 41.97±6.12, right: 42.91±6.43) and thalamus (left: 46.58±7.71, right: 49.11±7.10)) were significantly lower than that in the control group (caudate nucleus (left: 41.38±7.05, right: 41.63±6.85), globus pallidum (left: 45.65±8.35, right: 45.53±8.94), putamen nucleus (left: 48.49±8.78, right: 48.99±8.88) and thalamus (left: 54.32±11.94, right: 56.21±11.98), F=13.58, 10.56, 12.11, 10.06, 8.59, 8.23, 9.57, 8.30, P=0.000, 0.002, 0.005, 0.005, 0.001, 0.002, 0.003, 0.005, respectively). The whole brain mean CBF values of each subject were also extracted and compared bewteen groups, and mean CBF values (ml·100 g^-1·min^-1) in PD patients (42.14±9.61) decreased significantly than those in the control group (51.59±9.67, F=16.42, P<0.01), and there was a 18.31% decrement in whole brain mean CBF in the patient group. However, rCBF values for almost all subcortical ROIs of the patients significantly increased when compared with the control group. Conclusions The decreased absolute cerebral blood perfusion involved not only subcortical regions, but also the whole brain level in the course of PD. The CBF metabolism in patients with PD may have been redistributed, with relative hyperperfusion in the subcortical brain regions contrast to the whole brain perfusion level of patients themselves.