Using Normalized Carcinoembryonic Antigen and Carbohydrate Antigen 19 to Predict and Monitor the Efficacy of Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer.

Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are established prognostic biomarkers for patients with gastric cancer. However, their potential as predictive markers for neoadjuvant chemotherapy (NACT) efficacy has not been fully elucidated. METHODS: We conducted a retrospective analysis to determine values of CEA and CA19-9 prior to NACT (pre-NACT) and after NACT (post-NACT) in 399 patients with locally advanced gastric cancer (LAGC) who received intended NACT and surgery. RESULTS: Among the 399 patients who underwent NACT plus surgery, 132 patients (33.1%) had elevated pre-NACT CEA/CA19-9 values. Furthermore, either pre-NACT or post-NACT CEA /CA19-9 levels were significantly associated with prognosis (p = 0.0023) compared to patients with non-elevated levels. Moreover, among the patients, a significant proportion (73/132, 55.3%) achieved normalized CEA/CA19-9 following NACT, which is a strong marker of a favorable treatment response and survival benefits. In addition, the patients with normalized CEA/CA19-9 also had a prolonged survival compared to those who underwent surgery first (p = 0.0140), which may be attributed to the clearance of micro-metastatic foci. Additionally, the magnitude of CEA/CA19-9 changes did not exhibit a statistically significant prognostic value. CONCLUSIONS: Normalization of CEA/CA19-9 is a strong biomarker for the effectiveness of treatment, and can thus be exploited to prolong the long-term survival of patients with LAGC.

A Modified Vancomycin Molecule Confers Potent Inhibitory Efficacy against Resistant Bacteria Mediated by Metallo-ß-Lactamases.

Multidrug-resistant bacterial infections mediated by metallo-ß-lactamases (MßLs) have grown into an emergent health threat, and development of novel antimicrobials is an ideal strategy to combat the infections. Herein, a novel vancomycin derivative Vb was constructed by conjugation of triazolylthioacetamide and vancomycin molecules, characterized by reverse-phase high performance liquid chromatography (HPLC) and confirmed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). The biological assays revealed that Vb effectively inhibited S. aureus and methicillin-resistant S. aureus (MRSA), gradually increased the antimicrobial effect of ß-lactam antibiotics (cefazolin, meropenem and penicillin G) and exhibited a dose-dependent synergistic antibacterial effect against eight resistant strains tested, which was confirmed by the time-kill curves determination. Most importantly, Vb increased the antimicrobial effect of meropenem against the clinical isolates EC08 and EC10 and E. coli producing ImiS and CcrA, resulting in a 4- and 8-fold reduction in MIC values, respectively, at a dose up to 32 µg/mL. This work offers a promising scaffold for the development of MßLs inhibitors, specifically antimicrobials for clinically drug-resistant isolates.

Ligustilide Improves Cognitive Impairment via Regulating the SIRT1/IRE1α/XBP1s/CHOP Pathway in Vascular Dementia Rats.

Vascular dementia (VaD), the second cause of dementia, is caused by chronic cerebral hypoperfusion, producing progressive damage to cerebral cortex, hippocampus, and white matter. Ligustilide (LIG), one of the main active ingredients of Angelica sinensis, exerts the neuroprotective effect on neurodegenerative diseases. However, the mechanism remains unclear. An in vivo model of bilateral common carotid artery occlusion and in vitro model of oxygen glucose deprivation (OGD) were employed in this study. LIG (20 or 40 mg/kg/day) was intragastrically administered to the VaD rats for four weeks. The results of the Morris water maze test demonstrated that LIG effectively ameliorated learning and memory deficiency in VaD rats. LIG obviously relieved neuronal oxidative stress damage by increasing the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) and decreasing the level of malondialdehyde (MDA) in VaD rats. Nissl staining showed that LIG increased the number of the Nissl body in VaD rats. After LIG administration, the apoptotic-related protein, Bax, was decreased and Bcl-2 was increased in the hippocampus of VaD rats. Moreover, the expressions of sirtuin 1 (SIRT1) and protein disulfide isomerase (PDI) were decreased, binding immunoglobulin protein (BIP) and phospho-inositol-requiring enzyme-1α (P-IRE1α), X-box binding protein 1 (XBP1s), and C/EBP-homologous protein (CHOP) were increased in VaD rats. After LIG treatment, these changes were reversed. The immunofluorescence results further showed that LIG upregulated the expression of SIRT1 and downregulated the expression of P-IRE1α in VaD rats. In addition, in vitro experiment showed that EX-527 (SIRT1 inhibitor) partly abolished the inhibitory effect of LIG on the IRE1α/XBP1s/CHOP pathway. In conclusion, these studies indicated that LIG could improve cognitive impairment by regulating the SIRT1/IRE1α/XBP1s/CHOP pathway in VaD rats.

Ligustilide ameliorates cognitive impairment via AMPK/SIRT1 pathway in vascular dementia rat.

Vascular dementia (VaD) is the second cause of dementia after Alzheimer's disease. Ligustilide (LIG) is one of the main active ingredients of traditional Chinese medicines, such as Angelica. Studies have reported that LIG could protect against VaD. However, the mechanism is still confused. In this study, we employed a bilateral common carotid artery occlusion rat model to study. LIG (20 or 40 mg/kg/day) and Nimodipine (20 mg/kg) were orally administered to the VaD rats for four weeks. Morris water maze test showed that LIG effectively ameliorated learning and memory impairment in VaD rats. LIG obviously reduced neuronal oxidative stress damage and the level of homocysteine in the brain of VaD rats. Western blot results showed that pro-apoptotic protein Bax and cleaved caspase 3 increased and anti-apoptotic protein Bcl-2 decreased in the hippocampi of VaD rats. But after LIG treatment, these changes were reversed. Moreover, Nissl staining result showed that LIG could reduce neuronal degeneration in VaD rats. Furthermore, LIG enhanced the expressions of P-AMPK and Sirtuin1(SIRT1) in VaD rats. In conclusion, these studies indicated that LIG could ameliorate cognitive impairment in VaD rats, which might be related to AMPK/SIRT1 pathway activation.

Vancomycin-related convulsion in a pediatric patient with neuroblastoma: A case report and review of the literature.

BACKGROUND: Vancomycin is often used as an anti-infective drug in patients receiving anti-tumor chemotherapy. There are concerns about its adverse drug reactions during treatment, such as nephrotoxicity, ototoxicity, hypersensitivity reactions, etc. However, potential convulsion related to high plasma concentrations of vancomycin in children receiving chemotherapy has not been reported. CASE SUMMARY: A 3.9-year-old pediatric patient with neuroblastoma receiving vancomycin to treat post-chemotherapy infection developed an unexpected convulsion. No other potential disease conditions could explain the occurrence of the convulsion. The subsequently measured overly high plasma concentrations of vancomycin could possibly provide a clue to the occurrence of this convulsion. The peak and trough plasma concentrations of vancomycin were 59.5 mg/L and 38.6 mg/L, respectively, which were much higher than the safe range. Simulation with the Bayesian approach using MwPharm software showed that the area under the concentration-time curve over 24 h was 1086.6 mg· h/L. Therefore, vancomycin was immediately stopped and teicoplanin was administered instead combined with meropenem and fluconazole as the anti-infective treatment strategy. CONCLUSION: Unexpected convulsion occurring in a patient after chemotherapy is probably due to toxicity caused by abnormal pharmacokinetics of vancomycin. Overall evaluation and close therapeutic drug monitoring should be conducted to determine the underlying etiology and to take the necessary action as soon as possible.

Functional Division Between the RecA1 and RecA2 Proteins in Myxococcus xanthus.

Myxococcus xanthus DK1622 has two RecA genes, recA1 (MXAN_1441) and recA2 (MXAN_1388), with unknown functional differentiation. Herein, we showed that both recA genes were induced by ultraviolet (UV) irradiation but that the induction of recA1 was more delayed than that of recA2. Deletion of recA1 did not affect the growth but significantly decreased the UV-radiation survival, homologous recombination (HR) ability, and induction of LexA-dependent SOS genes. In contrast, the deletion of recA2 markedly prolonged the lag phase of bacterial growth and increased the sensitivity to DNA damage caused by hydrogen peroxide but did not change the UV-radiation resistance or SOS gene inducibility. Protein activity analysis demonstrated that RecA1, but not RecA2, catalyzed DNA strand exchange (DSE) and LexA autocleavage in vitro. Transcriptomic analysis indicated that RecA2 has evolved mainly to regulate gene expression for cellular transportation and antioxidation. This is the first report of functional divergence of duplicated bacterial recA genes. The results highlight the evolutionary strategy of M. xanthus cells for DNA HR and genome sophistication.

[Isolation of Heavy Metal Immobilizing and Plant Growth-Promoting Bacteria and Its Effects on Reducing Heavy Metal Accumulation in Wheat].

The effects of heavy metal contamination on farmland continues to worsen progressively with an increase in anthropogenic activities such as industrial pollution and mining. Excess Cd and Pb in agricultural soils enter the food chain and adversely affect all organisms. Therefore, it is important to find an eco-friendly way to reduce heavy metal accumulation in crops. Based on their heavy metal resistance and growth-promoting characteristics, functional bacterial strains were screened and their effects on growth and heavy metal accumulation in wheat were verified via shaking flask adsorption and sand culture tests. Eighteen functional strains were isolated from the rhizospheric soil of Salvia setaria. Among them, Bacillus megaterium N3 and Serratia liquefaciens H12 were most effective at resisting high Cd (650 mg·L-1) and Pb (2700 mg·L-1) concentrations, and at producing indole-3-acetic acid (IAA) (56.6 mg·L-1and 69.1 mg·L-1, respectively), siderophores, and 1-Amino-1-cyclopropanecarboxylic acid (ACC) deaminase. Static incubation experiments showed that strains N3 and H12 significantly increased the NH4+ concentration and pH, and decreased the Cd (63.1%-73.8%) and Pb (69.1%-81.8%) concentration in solution. In sand cultures, strains N3 and H12 not only increased the dry weight of wheat roots (47.2%-97.4%) and shoots (65.3%-153%) significantly, but also significantly reduced the Cd (49.2%-68.3%) and Pb (27.4%-84.5%) content in wheat roots and shoots. Thus, the results provide strain resources and a theoretical basis for the remediation of Cd- and Pb-contaminated farmlands for the safer production of crops.

[Drug management of pediatric acute respiratory distress syndrome].

This article reviewed the Consensus Recommendations on Pediatric Acute Respiratory Distress Syndrome (ARDS) from the Pediatric Acute Lung Injury Consensus Conference in 2015 and the literature related to drug management of ARDS. The main points of drug management of pediatric ARDS were summarized.