Scavenger Receptor Class B Type I Deficiency Induces Iron Overload and Ferroptosis in Renal Tubular Epithelial Cells via Hypoxia-Inducible Factor-1α/Transferrin Receptor 1 Signaling Pathway.

Aims: Scavenger receptor class B type I (SRBI) promotes cell cholesterol efflux and the clearance of plasma cholesterol. Thus, SRBI deficiency causes abnormal cholesterol metabolism and hyperlipidemia. Studies have suggested that ferroptosis is involved in lipotoxicity; however, whether SRBI deficiency could induce ferroptosis remains to be investigated. Results: We knocked down or knocked out SRBI in renal HK-2 cells and C57BL/6 mice to determine the expression levels of ferroptosis-related regulators. Our results demonstrated that SRBI deficiency upregulates transferrin receptor 1 (TFR1) expression and downregulates ferroportin expression, which induces iron overload and subsequent ferroptosis in renal tubular epithelial cells. TFR1 is known to be regulated by hypoxia-inducible factor-1α (HIF-1α). Next, we investigated whether SRBI deletion affected HIF-1α. SRBI deletion upregulated the mRNA and protein expression of HIF-1α, and promoted its translocation to the nucleus. To determine whether HIF-1α plays a key role in SRBI-deficiency-induced ferroptosis, we used HIF-1α inhibitor and siHIF-1α in HK-2 cells, and found that downregulation of HIF-1α prevented SRBI-silencing-induced TFR1 upregulation and iron overload, and eventually reduced ferroptosis. The underlying mechanism of HIF-1α activation was explored next, and the results showed that SRBI knockout or knockdown may upregulate the expression of HIF-1α, and promote HIF-1α translocation from the cytoplasm into the nucleus via the PKC-ß/NF-κB signaling pathway. Innovation and Conclusion: Our study showed, for the first time, that SRBI deficiency induces iron overload and subsequent ferroptosis via the HIF-1α/TFR1 pathway.

Identification of the communal pathogenesis and immune landscape between viral myocarditis and dilated cardiomyopathy.

AIMS: Studies have confirmed that viral myocarditis (VMC) is one of the risk factors for dilated cardiomyopathy (DCM). The molecular mechanisms underlying the progression from VMC to DCM remain unclear and require further investigation. METHODS AND RESULTS: The mRNA microarray datasets GSE57338 (DCM) and GSE1145 (VMC) were obtained from the Gene Expression Omnibus database. The candidate key genes were further screened using weighted correlation network analysis (WGCNA), protein-protein interaction and external dataset validation, and the correlation between the candidate key genes and immune cells and the signalling pathways of the candidate key genes were observed by enrichment analysis and immune infiltration analysis. The expression of key genes was validated in the external dataset GSE35182. The crosstalk genes between DCM and VMC were mainly enriched in 'transcriptional misregulation in cancer', 'FoxO signalling pathway', 'AGE-RAGE signalling pathway in diabetic complications', 'thyroid hormone signalling pathway', 'AMPK signalling pathway', and other signalling pathways. The immune infiltration analysis indicated that VMC was mainly associated with resting dendritic cells and M0 macrophages, while DCM was mainly associated with monocytes, M0 macrophages, CD8+ T cells, resting CD4 memory T cells, naive CD4+ T cells, and resting mast cells. In DCM-related dataset GSE57338 and VMC-related dataset GSE1145, a total of 18 candidate key genes were differentially expressed. BLC6, FOXO1, and UBE2M were identified as the key genes that lead to the progression from VMC to DCM by GSE35182. CONCLUSIONS: Three key genes (BLC6, FOXO1, and UBE2M) were identified and provided new insights into the diagnosis and treatment of VMC with DCM.

SAA1 deficiency alleviates cardiac remodeling by inhibiting NF-κB/p38/JNK and TGFß/Smad pathways.

Heart failure (HF) is the end stage of the progression of many cardiovascular diseases. Cardiac remodeling is the main pathophysiological process of cardiac function deterioration in HF patients. Inflammation is a key factor that stimulates cardiomyocyte hypertrophy, fibroblast proliferation, and transformation leading to myocardial remodeling, which severity is significantly related to the prognosis of patients. SAA1 (Serum amyloid A1) is a lipid-binding protein that was an important regulator involved in inflammation, whose biological functions in the heart remain rarely known. In this research, we intended to test the role of SAA1 in SAA1-deficient (SAA1-/- ), and wild-type mice were exposed to transverse aortic banding surgery to establish the model of cardiac remodeling. Besides, we assessed the functional effects of SAA1 on cardiac hypertrophy and fibrosis. The expression of SAA1 was increased in the mice transverse aortic banding model induced by pressure overload. After 8 weeks of transverse aortic banding, SAA1-/- mice displayed a lower level of cardiac fibrosis than wild-type mice, but did not significantly influence the cardiomyocyte hypertrophy. In addition, there was also no significant difference in cardiac fibrosis severity between wild-type-sham and knockout-sham mice. These findings are the first to reveal SAA1 absence hinders cardiac fibrosis after 8 weeks of transverse aortic banding. Furthermore, SAA1 deficiency had no significant effect on cardiac fibrosis and hypertrophy in the sham group in this study.

Association of Obesity Indices with Diabetic Kidney Disease and Diabetic Retinopathy in Type 2 Diabetes: A Real-World Study.

Background: Diabetic microvascular complications mainly include diabetic kidney disease (DKD) and diabetic retinopathy (DR). Obesity was recognized as a risk factor for DKD, while the reported relationship between obesity and DR was inconsistent. Moreover, whether the associations can be attributed to C-peptide levels is unknown. Methods: Data from 1142 sequential inpatients with T2DM at Xiangyang Central Hospital between June 2019 and March 2022 were extracted retrospectively from the electronic medical record system. The associations between four obesity indices (body mass index (BMI), waist-hip circumference ratio (WHR), visceral fat tissue area (VFA), and subcutaneous fat tissue area (SFA)) and DKD and DR were evaluated. Whether the associations can be attributed to C-peptide levels was also explored. Results: Obesity was a risk factor for DKD after adjusting for sex, HbA1c, TG, TC, HDL, LDL, smoking history, education, duration of diabetes, and insulin use (obesity indices: BMI (OR 1.050: 95% CI: 1.008-1.094; P = 0.020); WHR (OR 10.97; 95% CI: 1.250-92.267; P = 0.031); VFA (OR 1.005; 95% CI: 1.001-1.008; P = 0.008)), but it became insignificant after further adjusting for fasting C-peptide. The associations between BMI, WHR, VFA, and DKD might be U-shaped. Obesity and FCP tended to protect against DR; however, they became insignificant after adjusting for multiple potential confounders. C2/C0 (the ratio of the postprandial serum C-peptide to fasting C-peptide) was a protective factor for both DKD (OR 0.894, 95% CI: 0.833-0.959, P < 0.05) and DR (OR 0.851, 95% CI: 0.787-0.919; P < 0.05). Conclusions: Obesity was a risk factor for DKD, and the effect may be attributable to C-peptide, which represents insulin resistance. The protective effect of obesity or C-peptide on DR was not independent and could be confounded by multiple factors. Higher C2/C0 was associated with both decreased DKD and DR.

Empagliflozin attenuates the renal tubular ferroptosis in diabetic kidney disease through AMPK/NRF2 pathway.

Renal tubular damage plays a key role in the pathogenesis of diabetic kidney disease (DKD), and one of the main pathological process associated with DKD in diabetic mice is the ferroptosis, a novel form of cell death caused by iron-dependent lipid peroxidation. Several researches suggested that empagliflozin may treat renal injury, but its effects on diabetic-related ferroptosis and underlying mechanisms were not fully elucidated. In this study, the influence of empagliflozin on renal injury was evaluated in vivo and in vitro in a mouse model and in high-glucose (HG) or Erastin-stimulated renal HK-2 cell line, respectively. Ferroptosis-related markers were assessed, including GSH, labile iron levels, and ferroptosis regulators by Western blot, qRT-PCR, immunohistochemistry, and immunofluorescence. The level of malondialdehyde (MDA) and the fluorescence intensity of BODIPY probe indicated the level of lipid peroxidation. It was demonstrated that solute carrier family 7, member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were less expressed in renal biopsy samples from patients affected by DKD than in those from non-diabetic renal disease patients (NDRD), proving the ferroptosis of tubular epithelial cells in case of DKD. Furthermore, empagliflozin markedly decreased the ferroptosis impairment in DKD mice, as well as in HG model of HK-2 cells. Our investigations showed the ability of empagliflozin to suppress ferroptosis was partially countered by AMP-activated protein kinase (AMPK) inhibitor, which led to a reduction of the nuclear translocation of the antioxidant transcription factor NFE2-related factor 2 (NRF2) and downregulation of target genes such as GPX4, ferritin heavy chain 1 (FTH1), and SLC7A11, while AMPK agonists were responsible for the enhancement of the protective effects of empagliflozin. Taken together, our findings showed that empagliflozin may prevent the development of ferroptosis by promoting the AMPK-mediated NRF2 activation pathway, providing important insights for possible novel treatment approaches for DKD.

Alterations of Renal Function in Patients with Diabetic Kidney Disease: A BOLD and DTI Study.

Objectives: Our study aims to determine the patterns of renal oxygenation changes and microstructural changes by BOLD and DTI with deteriorating kidney function in patients with diabetic kidney disease (DKD). Methods: Seventy-two patients with type 2 diabetes mellitus (DM) and twenty healthy controls (HCs) underwent laboratory examinations, and renal BOLD and DTI images were obtained on a 3T-MRI machine. R2 ∗ , fractional anisotropy (FA), and average diffusion coefficient (ADC) values were evaluated. DM patients were divided into three subgroups (Group-DI/DII/DIII, based on urinary albumin-creatinine ratio (UACR)) and a nondiabetic kidney disease group (Group-NDKD). D-value and MCR of R2 ∗ and FA were proposed to evaluate the differentiation between medulla and cortex of the individual kidney among HCs and three subgroups for reducing individual differences. Comparisons were made between NDKD and kidney function-matched DKD patients. Correlations between MRI parameters and renal clinical indices were analyzed. Results: Compared with Group-HC/DI, medullary R2 ∗ and FA values were significantly different in Group-DII/III. The D-value of R2 ∗ and FA in Group-III were significantly smaller than that in Group-HC. However, only MCR of R2 ∗ in Group-III was significantly smaller than that in HCs. Medullary R2 ∗ and FA were negatively associated with serum creatinine (SCr) and cystatin C (Cys C) and positively associated with eGFR. Conclusions: With renal function declining, BOLD and DTI could capture alterations including the first rising and then falling medullary R2 ∗ , continuously declining medullary FA, and apparent cortex-medullary differentiation in DKD patients. The MRI parameters showed renal changes accompanied by varying degrees of albuminuria, sharing common involvement in DKD and NDKD patients, but it was hard to distinguish between them. BOLD seemed more sensitive than DTI in identifying renal cortex-medullary differentiation.

The Correlation between Ferroptosis and m6A Methylation in Patients with Acute Kidney Injury.

OBJECTIVE: The present research analyzed the correlation between N6-methyladenosine (m6A) methylation and ferroptosis associated genes (FAGs) in acute kidney injury (AKI) patients. METHODS: Bioinformatics analysis of microarray profiles (GSE30718) was performed to select differential expression genes (DEGs). FAGs are derived from systematic analysis of the aberrances and functional implications. The m6A methylation related genes were derived from the molecular characterization and clinical significance of m6A modulators. The multi-gene correlation of ferroptosis and M6A methylation modification was displayed. Then, the CIBERSORT algorithm was used to analyze the proportions of 22 immune cell infiltration. RESULTS: In total, 349 DEGs were extracted between the AKI and control samples, among which 172 genes were upregulated and 177 were downregulated. FAGs (SLC1A5, CARS, SAT1, ACSL4, NFE2L2, TFRC, and MT1G) and m6A methylation related genes (YTHDF3, WTAP, and IGF2BP3) were significantly increased in AKI patients (p < 0.05). FAGs (SAT1, ACSL4, and NFE2L2) were positively correlated with the expression level of m6A methylation genes (p < 0.05). NFE2L2 has high diagnostic value, and the level of NFE2L2 was negatively correlated with the degree of follicular helper T (TFH) cell infiltration. CONCLUSION: Our research could provide a new theoretical basis for the pathogenesis and immune mechanism of AKI.

The recruitment mechanisms and potential therapeutic targets of podocytes from parietal epithelial cells.

Podocytes are differentiated postmitotic cells which cannot be replaced after podocyte injury. The mechanism of podocyte repopulation after injury has aroused wide concern. Parietal epithelial cells (PECs) are heterogeneous and only a specific subpopulation of PECs has the capacity to replace podocytes. Major progress has been achieved in recent years regarding the role and function of a subset of PECs which could transdifferentiate toward podocytes. Additionally, several factors, such as Notch, Wnt/ß-catenin, Wilms' tumor-1, miR-193a and growth arrest-specific protein 1, have been shown to be involved in these processes. Finally, PECs serve as a potential therapeutic target in the conditions of podocyte loss. In this review, we discuss the latest observations and concepts about the recruitment of podocytes from PECs in glomerular diseases as well as newly identified mechanisms and the most recent treatments for this process.

Endoplasmic Reticulum Stress in Diabetic Nephrology: Regulation, Pathological Role, and Therapeutic Potential.

Recent progress has been made in understanding the roles and mechanisms of endoplasmic reticulum (ER) stress in the development and pathogenesis of diabetic nephropathy (DN). Hyperglycemia induces ER stress and apoptosis in renal cells. The induction of ER stress can be cytoprotective or cytotoxic. Experimental treatment of animals with ER stress inhibitors alleviated renal damage. Considering these findings, the normalization of ER stress by pharmacological agents is a promising approach to prevent or arrest DN progression. The current article reviews the mechanisms, roles, and therapeutic aspects of these findings.

Empagliflozin Regulates the AdipoR1/p-AMPK/p-ACC Pathway to Alleviate Lipid Deposition in Diabetic Nephropathy.

BACKGROUND: Abnormal lipid deposition in the progress of diabetic nephropathy (DN) plays an important role in a number of studies that have shown that SGLT2 inhibitor (SGLT2i) empagliflozin plays an important role in lipid metabolism, but its mechanism is still unclear. METHODS: We aimed to explore the effect of empagliflozin on lipid levels in kidney cancer patients with DN and postoperative patients without DN kidney carcinoma; the patients with DN showed ectopic lipid deposition. In type 2 diabetes model mice induced by streptozotocin (STZ) and a high-fat diet, combined AMPK plus empagliflozin or empagliflozin inhibitor plus compound C was applied, followed by analyses of the blood, urine and kidney indexes to observe the correlation between SGLT2i and AMPK and lipid metabolism in diabetic kidney disease. We determined whether DN in patients with renal tubular atrophy involved lipid metabolism. RESULTS: In clinical specimens, the adiponectin receptor AdipoR1 was reduced, and the phosphorylation acetyl-CoA carboxylase (p-ACC) was increased. In vitro and in vivo pathological immunofluorescence and Western blotting confirmed that, under the condition of high glucose, malpighian tubules displayed ectopic lipid deposition and expressed related lipid parameters accompanied by fibrosis. Empagliflozin intervention reduced lipid deposition fibrosis and renal tubular atrophy, and the addition of compound C promoted disease progression. Moreover, siAdipoR1 transfection proved that AdipoR1 affected P-AMPK and then p-ACC affected lipid metabolism in renal tubular cells. CONCLUSION: According to the above experimental results, empagliflozin could reduce lipid metabolism of DN through AdipoR1/P-AMPK/P-ACC pathway and delay DN progress.

Co-Expression Network Analysis Identified LTF in Association with Metastasis Risk and Prognosis in Clear Cell Renal Cell Carcinoma.

OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer in adults. The 5-year survival rate of patients with advanced ccRCC is less than 30%. Lack of potential biomarkers for treatment and prognosis is a limitation for early diagnosis and treatment of ccRCC. METHODS: We collected microarray profiles of 39 ccRCC and matched normal samples to identify differential expression genes (DEGs). Then, a weighted gene co-expression network analysis (WGCNA) was constructed to identify gene modules associated with the metastasis in ccRCC. The Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (HPA, https://www.proteinatlas.org/) database were used for verification set. Finally, we used biological experiments to preliminary investigate the impact of LTF on the tumor biological behavior of ccRCC, including proliferation, migration, invasion, and apoptosis. RESULTS: A total of 15 genetic modules were identified, and the light-green module is considered the most relevant to tumor metastasis. (P = 0.02, R2 = -0.4). Protein-protein interaction (PPI) network was performed to identify the hub nodes in the light-green module. Finally, combining the results of PPI, WGCNA and DEGs, lactotransferrin (LTF) gene was regarded as "real" hub genes for cancer metastasis risk. LTF was subsequently validated using the TCGA database. Immunohistochemistry confirmed that the expression of LTF in ccRCC tumor tissue was significantly lower than that in normal tissue based on the HPA database. Intriguingly, patients with low expression of LTF had lower survival rates (HR = 0.66, 95% CI: 0.49-0.89, P = 0.0067), the expression level of the sample was negatively correlated with tumor stage (P = 0.0385), and patients with low expression of LTF gene were more likely to have distant metastasis (P = 0.038). Overexpression of LTF inhibited the proliferation, migration, invasion and promoted apoptosis of human ccRCC cells in vitro. CONCLUSION: LTF might be a novel prognostic biomarker for ccRCC.

The Role of Arachidonic Acid Metabolism in Myocardial Ischemia-Reperfusion Injury.

Patients with myocardial ischemic diseases or who are undergoing one of various heart treatments, such as open heart surgery, coronary artery bypass grafting, percutaneous coronary artery intervention or drug thrombolysis, face myocardial ischemia-reperfusion injury (MIRI). However, no effective treatment is currently available for MIRI. To improve the prognosis of people with cardiovascular disease, it is important to research the mechanism of MIRI. Arachidonic acid (AA) is one of the focuses of current research. The various metabolic pathways of AA are closely related to the development of cardiovascular disease, and the roles of various metabolites in ischemia-reperfusion injury have gradually been confirmed. AA is mainly metabolized in the cyclooxygenase (COX) pathway, lipoxygenase (LOX) pathway, and cytochrome P450 monooxygenase (CYP) pathway. This paper summarizes the progress of research on these three major AA metabolic pathways with respect to MIRI.

Evaluation of the association between the -1304T>G polymorphism in the promoter of the MKK4 gene and the risk of colorectal cancer: a PRISMA-compliant meta-analysis.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in China. Mitogen-activated protein kinase kinase 4 (MKK4) regulates tumorigenesis as a component of the MKK4 pathway. A number of studies have suggested a correlation between the MKK4 -1304T>G polymorphism and the risk of CRC. However, the results are still controversial. Therefore, we conducted a meta-analysis to obtain a more accurate assessment of the association between the MKK4 -1304T>G polymorphism and the risk of CRC. METHODS: Systematic literature searches were performed using PubMed, Embase, Cochrane Library, and CNKI. Four trials, including 1,255 cancer cases and 1,181 controls, were recruited in our study to assess the relationship of the MKK4 -1304T>G polymorphism with the risk of CRC. RESULTS: Four studies met our inclusion criteria and were finally included in the analysis, involving 1,255 cancer patients and 1,181 controls. Our meta-analysis revealed that the MKK4 -1304T>G polymorphism could reduce the risk of CRC (G vs. T: OR, 0.60, 95% CI: 0.48-0.76, P<0.0001; GG vs. TT: OR, 0.43, 95% CI: 0.29-0.62, P<0.0001; GG vs. TT + TG: OR, 0.50, 95% CI: 0.34-0.72, P=0.0003; TG + GG vs. TT: OR, 0.62, 95% CI: 0.53-0.73, P<0.0001; and TG vs. TT + GG: OR, 0.70, 95% CI: 0.59-0.82, P<0.0001). CONCLUSIONS: In conclusion, our meta-analysis showed that the MKK4 -1304T>G polymorphism was associated with the susceptibility to CRC. In the future, large and well-designed case-control studies are needed to validate our findings.

Bioinformatics-based discovery of the urinary BBOX1 mRNA as a potential biomarker of diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD) in the world. Emerging evidence has shown that urinary mRNAs may serve as early diagnostic and prognostic biomarkers of DKD. In this article, we aimed to first establish a novel bioinformatics-based methodology for analyzing the "urinary kidney-specific mRNAs" and verify their potential clinical utility in DKD. METHODS: To select candidate mRNAs, a total of 127 Affymetrix microarray datasets of diabetic kidney tissues and other tissues from humans were compiled and analyzed using an integrative bioinformatics approach. Then, the urinary expression of candidate mRNAs in stage 1 study (n = 82) was verified, and the one with best performance moved on to stage 2 study (n = 80) for validation. To avoid potential detection bias, a one-step Taqman PCR assay was developed for quantification of the interested mRNA in stage 2 study. Lastly, the in situ expression of the selected mRNA was further confirmed using fluorescent in situ hybridization (FISH) assay and bioinformatics analysis. RESULTS: Our bioinformatics analysis identified sixteen mRNAs as candidates, of which urinary BBOX1 (uBBOX1) levels were significantly upregulated in the urine of patients with DKD. The expression of uBBOX1 was also increased in normoalbuminuric diabetes subjects, while remained unchanged in patients with urinary tract infection or bladder cancer. Besides, uBBOX1 levels correlated with glycemic control, albuminuria and urinary tubular injury marker levels. Similar results were obtained in stage 2 study. FISH assay further demonstrated that BBOX1 mRNA was predominantly located in renal tubular epithelial cells, while its expression in podocytes and urothelium was weak. Further bioinformatics analysis also suggested that tubular BBOX1 mRNA expression was quite stable in various types of kidney diseases. CONCLUSIONS: Our study provided a novel methodology to identify and analyze urinary kidney-specific mRNAs. uBBOX1 might serve as a promising biomarker of DKD. The performance of the selected urinary mRNAs in monitoring disease progression needs further validation.

Which neoadjuvant chemotherapy regimen should be recommended for patients with advanced nasopharyngeal carcinoma?: A network meta-analysis.

BACKGROUND: The clinical application has widespread disagreement on the different regimens of neoadjuvant chemotherapy (NCT) in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). We conducted a network meta-analysis (NMA) to evaluate the efficacy of the different NCT regimens in the treatment of NPC. METHODS: A systematic literature search was performed using PubMed, Embase, and Cochran Library. Totally, 31 randomized controlled trials (RCTs) (n = 4062) met study selection criteria and were incorporated in this NMA study. RESULTS: Our study showed that certain NCT regimens improved the prognosis of patients, and found out the relative best solution for each endpoint, such as paclitaxel, carboplatin, and gemcitabine for 1-year overall survival (OS) rate, cisplatin, calcium folinate, and 5-fluorouracil for 2-year OS rate, vinorelbine and cisplatin (NP) for 3-year OS rate, cyclophosphamide, cisplatin, and 5-fluorouracil for 5-year OS rate, NP for complete remission rate, cisplatin and gemcitabine for overall remission rate of the primary tumor. In addition, for certain grade 3 and above toxicity, the results of the NMA reflected certain NCT regimens can reduce toxicity of chemoradiotherapy (CRT) to a minimum, such as NP for anemia, mucositis, and thrombocytopenia, paclitaxel, epirubicin, and cisplatin for neutropenia and skin toxicity. CONCLUSION: Our NMA showed that certain cisplatin-based NCT regimens improved the prognosis of patients with NPC and reduced the toxicity of CRT. However, in view of survival rate and response rate, the best NCT regimen is not entirely consistent. Therefore, which NCT regimen will benefit most patients will need further explored.

Cetuximab versus nimotuzumab for the treatment of advanced nasopharyngeal carcinoma: A network meta-analysis.

PURPOSE: We conducted a network meta-analysis to evaluate the efficacy and toxicity of cetuximab and nimotuzumab in the treatment of advanced nasopharyngeal carcinoma (NPC). METHODS: A systematic literature search was performed though Pubmed, Embase, Cochran Library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical (CBM) and Wanfang databases. Totally, 19 randomized controlled trials (RCTs) (n=1201) met the study selection criteria and were incorporated in this network meta-analysis. RESULTS: Compared with cetuximab, the results of network meta-analysis indicated that nimotuzumab may achieve higher complete remission rate (CRR) or overall remission rate (ORR) of the primary tumor, but no difference was noticed in 1- and 2-year overall survival (OS) rate and certain toxicities such as myelosuppression, radiodermatitis, mucositis and gastrointestinal reactions. Although nimotuzumab increased the 3-year OS rate, compared with cetuximab, this result needs to be interpreted cautiously because of the studies' heterogeneity. CONCLUSION: Even though we didn't find significant difference between cetuximab and nimotuzumab in terms of survival outcomes, nimotuzumab is more advantageous in short-term efficacy.

No association of TNF-α-308G/A polymorphisms with head and neck cancer risk: A PRISMA-compliant meta-analysis.

BACKGROUND: A number of studies had reported the association between tumor necrosis factor-alpha (TNF-α) gene polymorphisms and head and neck cancer (HNC) risk. However, the results remained controversial. Therefore, we performed a meta-analysis to derive a more precise evaluation of the association between TNF-α-308G/A polymorphism and overall HNC risk and evaluated influence of cancer types and ethnicities. METHODS: A systematic literature search was performed using Pubmed, Embase, Cochrane Library, and Web of science. In total, we identified 15 studies including 2005 cancer cases and 2876 controls to evaluate the association of TNF-α-308G/A polymorphism with risk for HNC. RESULTS: Overall, there was no significant association between TNF-α-308G/A polymorphism and the risk of HNC. Furthermore, subgroup analyses were performed according to the types of tumor and the ethnicities, we also found there was no significant association between TNF-α-308G/A polymorphism and the risk of NPC and OC, and European and Asian populations had no statistically significant difference in the relationship of TNF-α-308G/A polymorphism and HNC susceptibility. CONCLUSION: This meta-analysis indicates that the TNF-α-308G/A polymorphism is not associated with HNC risk. In the future, large and well-designed case-control studies are needed to validate our findings.

Low expression of nm23-H1 associates with poor survival of nasopharyngeal carcinoma patients: A prisma-compliant meta-analysis.

BACKGROUND: Developing a new reliable prognostic marker to predict the prognosis and supply better and more suitable therapy for patients with nasopharyngeal carcinoma (NPC) is urgent. Therefore, we performed this systematic review of the literature with meta-analysis to clarify and explore the associate expression of nm23-H1 with prognosis of NPC patients. METHODS: Literature research in Cochrane Library, PubMed, and EMBASE was performed up to July 2016. Eligible case-control studies of associate expression of nm23-H1 with prognosis of NPC patients were included. RESULTS: Nine studies met our inclusion criteria and were finally included for the analysis, involving 861 participants. Our meta-analysis revealed that the low expression of nm23-H1 in NPC was: RR = 2.13, 95% CI 1.15-3.95 and R = 2.56, 95% CI 2.03-3.22; and poorer overall survival (OS) rate was 3-year OS rate: RR: 0.55; 95% CI: 0.45-0.67 and 5-year OS rate: RR: 0.60; 95% CI: 0.52-0.69. Furthermore, the statistical significance was constant irrespective of different NPC subtypes. CONCLUSION: The low expression of nm23-H1 is associated with poorer prognosis in patients with NPC, suggesting that it is a prognostic factor and potential biomarker for survival in NPC.