Currently, there are many studies on the mechanism of antibiotic resistance in Mycobacterium tuberculosis (Mtb), but there are few studies on its regulatory mechanism. Post-translational modifications (PTMs) have been recognized for their important role in controlling cellular dynamics such as metabolism and stress response, but the relationship between PTMs and antibiotic resistance gradually attracted the attention of researchers. Here, we summarize the definition of PTMs, and the mechanisms of antibiotic resistance in M. tuberculosis and discuss how PTMs are involved in antibiotic resistance, in order to provide a new breakthrough for the development of new anti-Ttb drugs.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, has become a major human infectious disease. The existing first-line and second-line TB drugs have poor treatment outcomes in patients with MDR-TB and XDR-TB. There is an urgent need for new and better drugs to treat tuberculosis due to lengthy and complex treatment regimens and a rising problem of drug resistance. Microbial-derived natural products have revealed enormous reservoirs of as yet untapped lead compounds. In this review, we discuss the strategies that have been developed in bacteria and fungi to isolation of non-culturable microorganisms and activation of silent biosynthetic gene clusters involved in the study of microbial-derived natural products. This review also highlights recent advances in microbial-derived natural products with anti-tuberculosis activity using these methods.

BACKGROUNDAcute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common condition, which affects not only the quality of life of patients but also their prognosis. The purpose of this study was to explore the effects of an inhaled salbutamol sulfate solution and an inhalation suspension of the glucocorticoid budesonide that were atomized with heliox to treat patients with AECOPD.

METHODSTwenty-three patients with AECOPD were divided into a treatment group (He/O2 = 70%/30%) and a control group (N2/O2 = 70%/30%). The salbutamol sulfate and budesonide were administered by inhalation twice a day for 7 days. Vital signs, arterial blood gas levels, pulmonary function and the levels of serum myostatin (sMSTN) were measured and lung vibration imaging was performed.

RESULTSWe found that the PaO2 and PaCO2 values were not significantly different between the two groups at the various time points (P > 0.05). There were also no significant differences in any of the parameters of pulmonary function between the two groups. However, after baseline correction, the increase rate of the forced expiratory volume in one second (FEV1), the forced vital capacity (FVC), and the maximum minute ventilation (MVV) appeared to be significantly increased at some time points compared with the baseline (before treatment) in both groups (P < 0.05). Although the values of quantitative lung distribution (QLD) for different regions and the levels of sMSTN were slightly different between the two groups, the repeated measures analysis of variance (ANOVA) revealed that there were no significant differences between the two groups or within any group (P > 0.05).

CONCLUSIONAlthough the use of heliox as a driving gas can improve symptoms and benefit patients with AECOPD, the heliox treatment group did not have significant differences in arterial blood gases, lung function, lung vibration response imaging or the levels of sMSTN compared with the control group. (Chinese Clinical Trial Register Center ChiCTRTRC-00000273).

Administration, Inhalation ; Aged ; Albuterol ; administration & dosage ; therapeutic use ; Budesonide ; administration & dosage ; therapeutic use ; Drug Interactions ; Female ; Helium ; administration & dosage ; therapeutic use ; Humans ; Male ; Middle Aged ; Oxygen ; administration & dosage ; therapeutic use ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive ; drug therapy

BACKGROUNDElderly multiple organ dysfunction syndrome (MODS) patients receiving invasive mechanical ventilation have poor prognosis in intensive care units (ICUs). We studied the usefulness of four commonly used severity scores and extrapulmonary factors that affected weaning to predict outcome of such patients.

METHODSClinical data of 197 patients on admission to ICUs (from January 2009 to June 2012) were used retrospectively. The Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE III, Sample Acute Physiological Score (SAPS) II and MODS scores were calculated. All the patients were grouped into survivors and nonsurvivors according to the prognosis. Patients, who weaned from ventilator (n = 154), were subdivided into a successful weaning group and a failed weaning group. The receiver operating characteristic (ROC) curves and Logistic regression was used for prognostic and weaning assessment.

RESULTSBased on the outcomes, the areas under the ROC of APACHE II, APACHE III, SAPS II, and MODS were 0.837, 0.833, 0.824, and 0.837, respectively. The Logistic regression analysis revealed that the odds ratio (OR) of underlying lung diseases, serum albumin and creatinine, and the number of organ failures was 2.374, 0.920, 1.003, and 1.547. APACHE II scores on admission performed excellent (ROC: 0.921) on the weaning assessments.

CONCLUSIONSAPACHE II and MODS systems were marginally better for evaluating the prognosis of elderly MODS patients who received invasive mechanical ventilation. Underlying lung diseases, serum albumin, serum creatinine and the number of organ failures were independent prognostic factors. Using the APACHE II scores on admission before weaning may increase the likelihood of successful weaning. (ClinicalTrial.gov identifier NCT01802983).

Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Multiple Organ Failure ; pathology ; therapy ; Prognosis ; Respiration, Artificial ; methods ; Retrospective Studies