https://www.commed.vcu.edu/Chronic_Disease/2012/cochranrvwrschbias.pdf

The Cochrane Collaboration's tool for assessing risk of bias in randomised trials

PURPOSE
This meta-analysis was performed to compare the activity, efficacy and toxicity of platinum-based versus non-platinum-based chemotherapy in patients with advanced non-small-cell lung cancer.


METHODS
Randomized phase II and III clinical trials comparing first-line palliative platinum-based chemotherapy with the same regimen without platinum or with platinum replaced by a nonplatinum agent were identified by electronic searches of Medline, Embase, and Cancerlit, and hand searches of relevant abstract books and reference lists. Response rates, 1-year survival, and toxicity were analyzed. Subgroups of trials using third-generation agents were compared.


RESULTS
Thirty-seven assessable trials were identified including 7,633 patients. A 62% increase in the odds ratio (OR) for response was attributable to platinum-based therapy (OR, 1.62; 95% CI, 1.46 to 1.8; P < .0001). The 1-year survival rate was increased by 5% with platinum-based regimens (34% v 29%; OR, 1.21; 95% CI, 1.09 to 1.35; P = .0003). No statistically significant increase in 1-year survival was found when platinum therapies were compared to third-generation-based combination regimens (OR, 1.11; 95% CI, 0.96 to 1.28; P = .17). The toxicity of platinum-based regimens was significantly higher for hematologic toxicity, nephrotoxicity, and nausea and vomiting, but not for neurotoxicity, febrile neutropenia rate, or toxic death rate.


CONCLUSION
Response is significantly higher with platinum-containing regimens. One-year survival was not significantly prolonged when platinum-based therapies were compared with third-generation-based combination regimens. Toxicity is generally higher for platinum-based regimens.

The Best Manuscript 論文紹介 Platinum-based versus non-platinum-based chemotherapy in advanced non-small-cell lung cancer:A meta-analysis of the published literature〔含 解説者コメント〕

Fibrinolysis or Primary PCI in ST-segment Elevation Myocardial Infarction

Traditional Chinese medicine in COVID-19.

N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant and anti-inflammatory capacity is the biochemical basis used to treat several diseases related to oxidative stress and inflammation. The primary role of NAC as an antioxidant stems from its ability to increase the intracellular concentration of glutathione (GSH), which is the most crucial biothiol responsible for cellular redox imbalance. As an anti-inflammatory compound, NAC can reduce levels of tumor necrosis factor-alpha (TNF-α) and interleukins (IL-6 and IL-1β) by suppressing the activity of nuclear factor kappa B (NF-κB). Despite NAC’s relevant therapeutic potential, in several experimental studies, its effectiveness in clinical trials, addressing different pathological conditions, is still limited. Thus, the purpose of this chapter is to provide an overview of the medicinal effects and applications of NAC to human health based on current therapeutic evidence.

https://www.mdpi.com/2076-3921/10/6/967/pdf

N-Acetylcysteine (NAC): Impacts on Human Health

Ferroptosis is a newly discovered form of regulated cell death dependent on iron and reactive oxygen species (ROS). It directly or indirectly affects the activity of glutathione peroxidases (GPXs) under the induction of small molecules, causing membrane lipid peroxidation due to redox imbalances and excessive ROS accumulation, damaging the integrity of cell membranes. Ferroptosis is mainly characterized by mitochondrial shrinkage, increased density of bilayer membranes, and the accumulation of lipid peroxidation. Myocardial ischemia-reperfusion injury (MIRI) is an unavoidable risk event for acute myocardial infarction. Ferroptosis is closely associated with MIRI, and this relationship is discussed in detail here. This review systematically summarizes the process of ferroptosis and the latest research progress on the role of ferroptosis in MIRI to provide new ideas for the prevention and treatment of MIRI.

/pdf/ferroptosis-opportunities-and-challenges-in-myocardial-23rey3n7wl.pdf

Ferroptosis: Opportunities and Challenges in Myocardial Ischemia-Reperfusion Injury

Pulmonary fibrosis is a progressively aggravating lethal disease that is a serious public health concern. Although the incidence of this disease is increasing, there is a lack of effective therapies. In recent years, the pathogenesis of pulmonary fibrosis has become a research hotspot. p53 is a tumor suppressor gene with crucial roles in cell cycle, apoptosis, tumorigenesis, and malignant transformation. Previous studies on p53 have predominantly focused on its role in neoplastic disease. Following in-depth investigation, several studies have linked it to pulmonary fibrosis. This review covers the association between p53 and pulmonary fibrosis, with the aim of providing novel ideas to improve the clinical diagnosis, treatment, and prognosis of pulmonary fibrosis.

/pdf/p53-a-key-protein-that-regulates-pulmonary-fibrosis-5fhn5glqjr.pdf

p53: A Key Protein That Regulates Pulmonary Fibrosis.

6-Gingerol (6-G) is known to alleviate myocardial ischemia/reperfusion injury. However, the underlying molecular mechanisms of 6-G myocardial protection are not known. In this study, the protective effect of 6-G on ischemia/reperfusion (I/R) damage and whether such a mechanism was related to apoptosis inhibition and activation of phosphoinositide 3-kinases (PI3K)/serine/threonine kinase (Akt) signaling pathway were investigated. Rats were subjected to I/R in the presence or absence of 6-G and the changes of cardiac function, infarct size and histopathological changes, and the levels of cardiac troponin T, creatine kinase-MB, and myocardial apoptosis were examined. The expression of caspase-3, PI3K, p-Akt, and Akt was also determined. We found that 6-G (6 mg/kg) pretreatment significantly improved heart function and ameliorated infarct size and histopathological changes and cardiac troponin T and creatine kinase-MB levels induced by I/R. Moreover, pretreatment with 6-G significantly inhibited myocardial apoptosis and caspase-3 activation induced by I/R. 6-G also upregulated expression of PI3K, p-Akt, and Akt in myocardial tissues. Taken together, these findings suggest that 6-G inhibits apoptosis and activates PI3K/Akt signaling in response to myocardial I/R injury as a possible mechanism to attenuate I/R-induced injury in heart. These results might be important for developing novel strategies for preventing myocardial I/R injury.

/pdf/6-gingerol-activates-pi3k-akt-and-inhibits-apoptosis-to-3k5q683y29.pdf

6-Gingerol Activates PI3K/Akt and Inhibits Apoptosis to Attenuate Myocardial Ischemia/Reperfusion Injury

Citrus alkaline extracts prevent fibroblast senescence to ameliorate pulmonary fibrosis via activation of COX-2.

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal lung disease with poor prognosis and limited treatment options. N-acetylcysteine (NAC), an anti-oxidant drug, has promising potential in the treatment of IPF. In the present systematic review and meta-analysis, the efficacy and safety of NAC for IPF were investigated. The following databases were comprehensively searched for relevant studies published until August 2018: Pubmed, Embase, Cochrane library, Chinese National Knowledge Infrastructure, Wangfang Database, VIP and the Chinese Biology Medical Database. A total of 21 controlled trials assessing the efficacy and safety of NAC therapy for IPF were identified and primary outcomes [forced vital capacity (FVC), adverse side effects] and secondary outcomes [diffusing capacity for carbon monoxide (DLCO) and its percentage predicted value (DLCO%), vital capacity (VC), partial arterial oxygen pressure (PaO2), 6-min walking distance test and mortality] were extracted for the meta-analysis. The risk ratio and mean difference or standardized mean difference with 95% confidence interval were calculated using RevMan 5.3 software. Analysis of the pooled data revealed that, compared with control treatments (routine treatment or drugs other than anti-oxidants), NAC therapy reduced the decline in lung function, as indicated by the FVC and DLCO, and slowed the progression of the disease, as indicated by the PaO2, while complications and mortality were similar. These results suggest good efficacy, tolerability and safety of the treatment. Furthermore, subgroup analysis revealed that combined therapy including NAC for IPF might be more effective than NAC monotherapy, while oral administration of NAC was safer than inhalation. In conclusion, the results of the present review and meta-analysis provide important information that may serve as a guide regarding NAC therapy for IPF in clinical practice.

/pdf/efficacy-and-safety-of-n-acetylcysteine-therapy-for-1uaqpjpsem.pdf

Qi Wu

Papers

Ferroptosis: Opportunities and Challenges in Myocardial Ischemia-Reperfusion Injury

p53: A Key Protein That Regulates Pulmonary Fibrosis.

6-Gingerol Activates PI3K/Akt and Inhibits Apoptosis to Attenuate Myocardial Ischemia/Reperfusion Injury

Citrus alkaline extracts prevent fibroblast senescence to ameliorate pulmonary fibrosis via activation of COX-2.

Efficacy and safety of N‑acetylcysteine therapy for idiopathic pulmonary fibrosis: An updated systematic review and meta‑analysis