Sequence-dependent effects of hematoporphyrin derivatives (HPD) photodynamic therapy and cisplatin on lung adenocarcinoma cells.

BACKGROUND: Hematoporphyrin derivatives (HPD)-Photodynamic therapy (PDT) in combination with cisplatin (DDP) is an effective anticancer strategy. However, whether the order of combination affects efficacy has not been studied. METHODS: The human lung adenocarcinoma (LUAD) A549 cells were used as the study subjects. After A549 cells were treated with a single medication (PDT/DDP) or a sequential combination (PDT + DDP / DDP + PDT), the cell viability was assayed using the cell counting kit-8 method. Hoechst staining, Annexin-V/propidium iodide (PI) double staining, western blotting, and a real-time quantitative polymerase chain reaction (RT-qPCR) were performed to examine the mechanisms behind the combined effects. RESULTS: A synergistic impact between HPD-PDT and DDP was found. The cell viability in the PDT+DDP group was significantly lower than in the DDP+PDT group. A significant apoptotic profile and a high apoptotic rate were seen in the PDT + DDP group. The western blot showed that the expression levels of Bcl2-associated x(Bax) and cleaved-poly ADP-ribose polymerase (PARP) increased, and those of B-cell lymphoma-2 (Bcl-2) and Caspase-9 decreased in the PDT + DDP group. At the same time, the RT-qPCR revealed the upregulation of Bax and PARP mRNA and the downregulation of Bcl-2 and Caspase-9 mRNA. CONCLUSION: The order of the combination therapy (PDT + DDP / DDP + PDT) was important. The HPD-PDT followed by DDP significantly inhibited LUAD cell viability, which may be related to the mitochondrial apoptotic pathway.

Antibiotic de-escalation principle in elderly patients with chronic obstructive pulmonary disease complicated with severe pneumonia.

The present study investigated the clinical effect of antibiotic de-escalation therapy in elderly patients with chronic obstructive pulmonary disease (COPD) complicated with severe pneumonia. According to the parity method of hospitalization number, 86 cases were selected and divided into the observation and control group with 43 cases each. Based on empirical antibiotic application, levofloxacin and cephalosporin antibiotics were used in the control group. After treatment for 3 days, the regimen was adjusted to antibiotics active against Gram-positive (G+) and Gram-negative (G-) bacteria such as the third or fourth generation cephalosporin antibiotics, combined with aminoglycoside, or macrolide antibiotics according to their effects. The treatment effects were re-evaluated after 3-7 days. Finally, broad-spectrum antibiotics such as imipenem were chosen or adjusted by bacterial cultures and drug sensitivity results in the control group. Patients in the observation group were treated according to the principle of antibiotic de-escalation therapy. Antibiotics active against G+ and G- bacteria were chosen as the first round of medication. After 3 days, broad-spectrum antibiotics such as imipenem were added to the treatment regimen. After 7 days, the treatment was changed to narrow spectrum antibiotic administration if the disease was in remission, and the antibiotic regimen was adjusted based on bacterial culture and drug sensitivity results. The treatment results were compared. The mechanical ventilation rate, antibiotic courses, number of antibiotics used, and mortality of the observation group were significantly lower than those in the control group (P<0.05). After treatment, lung function improved, partial pressure of oxygen and blood oxygen saturation increased, and partial pressure of carbon dioxide decreased in both groups. The improvement of all of the above parameters were more significant in the observation group (P<0.05). After treatment, the ratio of neutrophils over white blood cells and C-reactive protein levels of the two groups decreased, respiratory failure index (RFI) increased, and the changes were significantly more pronounced in the observation group (P<0.05). In conclusion, following the antibiotic de-escalation principle to treat older patients with COPD complicated with severe pneumonia can reduce the number of antibiotics required, improve lung function and clinical effects, and is safe and effective.

The efficacy and safety of reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: A systematic review and meta-analysis.

CONTEXT: Reslizumab is a humanised anti-interleukin 5 monoclonal antibody that disrupts eosinophil maturation and promotes programmed cell death. OBJECTIVE: We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug in patients with inadequately controlled, eosinophilic asthma. DATA SOURCES: The search included the following databases: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. STUDY SELECTION: A literature review was performed to identify all published randomized double-blind, placebo-controlled trials of reslizumab for the treatment of inadequately controlled, eosinophilic asthma. DATA EXTRACTION: Two reviewers independently extracted and verified pre-defined data fields. RESULTS: Four publications including 5 RCTs that compared reslizumab with placebo. For the comparison of reslizumab with placebo, asthma exacerbation (odds ratio (OR) = 0.46, 95% confidence interval (CI) = 0.35 to 0.59, p <0.00001); a forced expiratory volume in 1 s (FEV1) (the standardized mean difference (SMD) = 0.16, 95%CI = 0.10 to 0.23, p <0.00001); Asthma Control Questionnaire (ACQ) score (the SMD = -0.26, 95%CI= -0.36 to -0.16, p <0.00001); blood eosinophil counts (the SMD = -475.62, 95%CI = -528.41 to -422.83, p <0.00001). Safety assessments included the proportion of individuals who withdrawn due to adverse event (AE) (OR = 0.60 95%CI = 0.38 to 1.17, p = 0.16) indicated that reslizumab was well tolerated. LIMITATIONS: The article didn't research the safety, efficacy of reslizumab with longer term. CONCLUSIONS: This meta-analysis indicates that reslizumab to be an effective and safe treatment for inadequately controlled, eosinophilic asthma.

[Experimental study on the theraputic effect of crescent Euphorbia on lewis lung cancer in mice].

OBJECTIVE: To observe the inhibitory effects of crescent euphorbia on tumor growth, immunoregulation, the side effect on the mice blood system, cell cycle and to investigate its effect on apoptosis of tumor cells. METHOD: Crescent euphorbia was administered gastrally to C57BL/6J mouse implanted with Lewis lung cancer for 12 days. Inhibition on tumor growth, immunoregulation,the side effect on the mice blood system and cell cycle were observed and its effect on apoptosis of lung cancer cells were investigated. RESULT: (1) Inhibitory rates of crescent euphorbia at doses of 7.5, 15, 30 g x kg(-1) and 60 g x kg(-1) were 0.61%, 16.93%, 32.81% and 58.26% respectively, significant differenel with those of controls at doses of 30 g x kg(-1) and 60 g x kg(-1)(P < 0.05). (2) Although no effect on thymus index in normal mouse at all dose of crescent euphorbia was found, spleen index in tumor-bear mice was reduced significantly at dose of 60 g x kg(-1)(P < 0.05). (3) No side effect on the miceblood system was found. (4) The percentage of S phase of cell cycle was increased in the group of crescent euphorbia at dose of 30 g x kg(-1), 60 g x kg(-1) and the apoptotic rate was (16.43 +/- 18.69)% and (24.37 +/- 15.48)% by flow eytometry (P < 0.05). The apoptotic index (AI)of these two groups were (4.00 +/- 7.50)% and (5.93 +/- 5.96)% by TUNEL, however apoptosis was found in the group at doses of 60 g kg(-1) (P < 0.01). CONCLUSION: Crescent euphorbia can inhibit the growth of Lewis lung cancer in mice, no side effection for the mice blood system and the effect might be associated with induction of apoptosis on cancer cells.