RESUMEN
Background: Carbapenems and ß-lactam and ß-lactamase inhibitors (BLBLIs) have been used empirically in nosocomial pneumonia, but their efficacy and safety are controversial. Objective: We carried out a systematic review with meta-analysis to evaluate the efficacy and safety of carbapenems versus BLBLIs against nosocomial pneumonia. Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, CNKI, Wangfang, VIP and Sinomed were searched systematically through April 29, 2023 for clinical trials comparing carbapenems with BLBLIs for treatment of nosocomial pneumonia. Random-effects models were used to evaluate the impact of treatment on the risk ratio (RR) of all-cause mortality, clinical response, microbiologic response, resistance by Pseudomonas aeruginosa, adverse effects (AEs), and serious adverse effects. The quality of the evidence was assessed with the Cochrane risk of bias tool. The review was registerted in the INPLASY (INPLASY202340113). Results: Seven randomized controlled trials containing 3306 patients met our inclusion criteria Our meta-analysis showed no significant difference in all-cause mortality (RR = 0.88, 95% confidence interval [CI] = 0.75-1.03, I2 = 0%) or clinical cure (1.02, 0.96-1.09, 30%) or clinical failure (1.19, 0.97-1.47, 0%) or microbiologic clinical cure (0.98, 0.89-1.06, 40%) or Pseudomonas aeruginosa resistance (RR 2.43, CI 0.86-6.81, 49%, P = 0.09) or adverse events (0.98, 0.93-1.02, 0%) between carbapenems groups versus BLBLIs groups, but a significant difference was found for severe adverse events (RR 0.83, CI 0.73-0.94, 0%). Conclusion: Differences in the prevalence of mortality, clinical cure, or clinical failure were not observed between carbapenems groups versus BLBLIs groups in terms of nosocomial pneumonia. The use of carbapenems was linked to a tendency towards the emergence of P. aeruginosa resistance, however, no statistically significant difference was observed.
RESUMEN
A pterygium is generally believed to be a chronic inflammatory lesion caused by external stimuli that develops from the conjunctiva and grows onto the cornea. Simple bare sclera excision is the most commonly used method to treat pterygium. However, the high postoperative recurrence rate of pterygium remains a persistent challenge. Mitomycin C (MMC) is an antineoplastic antibiotic that inhibits DNA, RNA, and protein synthesis. In recent years, although MMC has proven useful for the treatment of pterygium, its application has been controversial because of its clear toxicity and the possibility of ocular complications. In the current study, we prospectively recruited patients to receive or not receive a local injection of MMC (0.4 mg/ml). Follow-up was conducted with the patients to determine the postoperative recurrence rate of pterygium and/or to observe any ocular complications. The remarkable results demonstrated that MMC can decrease the postoperative recurrence rate of pterygium without leading to serious eye complications. Further results indicated that MMC can inhibit the activation of the NLRP3 inflammatory signalling pathway and thus downregulate the expression of downstream molecules, including IL-18 and IL-1ß. MMC also reduced the expression of inflammatory factors TGF-ß1, VEGF, and IL-6. In addition to influencing these factors, MMC suppressed neovascularization and the proliferation of corneal fibroblasts to effectively reduce the recurrence rate of pterygium. Taken together, our results provide a theoretical basis for the development of prevention and treatment strategies for pterygium and suggest that MMC is highly effective as an adjunctive treatment after excision of primary pterygia.
RESUMEN
Hepatocellular carcinoma (HCC) is one of the most serious cancers, with rapid progression and high mortality. However, chemotherapy of HCC is hindered by multi-drug resistance (MDR). It is urgent, therefore, to explore new approaches for overcoming MDR of HCC cells. Ubenimex, an inhibitor of CD13, has been used as an immuno-enhancer for treating hematological neoplasms and other solid tumors. Here, we demonstrate that Ubenimex can also reverse MDR in the HCC cell lines HepG2/5-FU and Bel7402/5-FU. Ubenimex inhibits the expression of the proto-oncogene, Pim-3, which is accompanied by decreased expression of BCL-2 and BCL-XL, decreased phosphorylation of Bad, and increased tumor apoptosis. Moreover, Ubenimex decreases expression of the MDR-associated proteins P-gp, MRP3 and MRP2 to enhance intracellular accumulation of Cisplatin, for which down-regulation of Pim-3 is essential. Our results reveal a previously uncharacterized function of Ubenimex in mediating drug resistance in HCC, which suggests that Ubenimex may provide a new strategy to reverse MDR and improve HCC sensitivity to chemotherapeutic drugs via its effects on Pim-3.
