Echo-Level SAR Imaging Simulation of Wakes Excited by a Submerged Body.

The paper introduces a numerical simulation method for Synthetic Aperture Radar (SAR) imaging of submerged body wakes by integrating hydrodynamics, electromagnetic scattering, and SAR imaging simulation. This work is helpful for better understanding SAR images of submerged body wakes. Among these, the hydrodynamic model consists of two sets of ocean dynamics closely related to SAR imaging, namely the wake of the submerged body and wind waves. For the wake, we simulated it using computational fluid dynamics (CFD) numerical methods. Furthermore, we compared and computed the electromagnetic scattering characteristics of wakes under various navigation parameters and sea surface conditions. Following that, based on the operational principles and imaging theory of synthetic aperture radar (SAR), we established the SAR raw echo signal of the wake. Employing a Range-Doppler (RD) algorithm, we generated simulated SAR images of the wake. The results indicate that utilizing Computational Fluid Dynamics (CFD) numerical methods enables the simulation of wake characteristics generated by the motion of a submerged body with different velocities. The backscattering features of wakes are closely associated with the relative orientation between the wake and the radar line of sight. Under specific wind speeds, the wake gets masked within the sea surface background, resulting in less discernible characteristics of the wake in SAR images. This suggests that at lower speeds of submerged body or under specific wind conditions, the detectability of the wake in SAR images significantly diminishes.

Mutational landscape of nasopharyngeal carcinoma based on targeted next-generation sequencing: implications for predicting clinical outcomes.

BACKGROUND: The aim of this study was to draw a comprehensive mutational landscape of nasopharyngeal carcinoma (NPC) tumors and identify the prognostic factors for distant metastasis-free survival (DMFS). METHODS: A total of forty primary nonkeratinizing NPC patients underwent targeted next-generation sequencing of 450 cancer-relevant genes. Analysis of these sequencing and clinical data was performed comprehensively. Univariate Cox regression analysis and multivariate Lasso-Cox regression analyses were performed to identify factors that predict distant metastasis and construct a risk score model, and seventy percent of patients were randomly selected from among the samples as a validation cohort. A receiver operating characteristic (ROC) curve and Harrell's concordance index (C-index) were used to investigate whether the risk score was superior to the TNM stage in predicting the survival of patients. The survival of patients was determined by Kaplan-Meier curves and log-rank tests. RESULTS: The twenty most frequently mutated genes were identified, such as KMT2D, CYLD, and TP53 et al. Their mutation frequencies of them were compared with those of the COSMIC database and cBioPortal database. N stage, tumor mutational burden (TMB), PIK3CA, and SF3B1 were identified as predictors to build the risk score model. The risk score model showed a higher AUC and C-index than the TNM stage model, regardless of the training cohort or validation cohort. Moreover, this study found that patients with tumors harboring PI3K/AKT or RAS pathway mutations have worse DMFS than their wild-type counterparts. CONCLUSIONS: In this study, we drew a mutational landscape of NPC tumors and established a novel four predictor-based prognostic model, which had much better predictive capacity than TNM stage.

Patterns of regional lymph node failure of locally advanced hypopharyngeal squamous cell carcinoma after first-line treatment with surgery and/or intensity-modulated radiotherapy.

BACKGROUND: To identify the spatial patterns of regional lymph node failure of locally advanced hypopharyngeal squamous cell carcinoma (SCC) after first-line treatment with surgery and/or intensity-modulated radiotherapy (IMRT). METHODS: We retrospectively obtained the clinicopathological characters of 123 hypopharyngeal SCC patients, and investigated the patterns of regional lymph node failure. Univariate and multivariate logistic regression were used to determine the risk factors of regional lymph node failure. RESULTS: Forty patients (32.5% of total patients) were suffered regional lymph node failure. In these patients, the ipsilateral neck level II nodal failure account for 55.0% (22/40) followed by level III 30.0% (12/40), level VIb 15.0% (6/40), level VII 15.0% (6/40), and level IV 5.0% (2/40). In addition, 17.5% (7/40) patients suffered contralateral neck level II nodal failure and 7.5% (3/40) patients suffered level III nodal failure. The common failure levels were the II (7/46, 15.2%), III (4/46, 8.7%), VIb (4/46, 8.7%), and VII (5/46, 10.9%) for treatment by surgery. The lymph node recurrence and persistent disease at levels II (19/77, 24.7%) and III (10/77, 13.0%) remained the major cause of failure following curative intent of IMRT. The postoperative radiation significantly decreased the risk of regional lymph node failure (OR = 0.082, 95% CI: 0.007-1.000, P = 0.049); and the radiologic extranodal extension significantly increased the risk of regional lymph node failure (OR = 11.07, 95% CI: 2.870-42.69, P < 0.001). CONCLUSIONS: Whatever the treatment modality, the lymph node failure at level II and III was the most popular pattern for hypopharyngeal SCC. Moreover, for patients who underwent surgery, the nodal failure at level VIb and VII was frequent. Thus, postoperative radiation of level VIb and VII may give rise to benefit to locally advanced hypopharyngeal SCC patients.

Boschniakia Rossica Polysaccharide Triggers Laryngeal Carcinoma Cell Apoptosis by Regulating Expression of Bcl-2, Caspase-3, and P53.

BACKGROUND Laryngeal cancer is a malignant head and neck tumor with high morbidity and high mortality in humans. Recently, treatments with Chinese medicines and their extracts have gradually received great attention, and studies suggest that Boschniakia rossica polysaccharide (BRP) has potential anti-tumor activity. Therefore, this study investigating the role of BRP in inducing apoptosis in human laryngeal carcinoma cells. MATERIAL AND METHODS The BRP was extracted with organic solvent and HR column. We treated Hep2 laryngeal carcinoma cells with different concentrations of BRP, then assessed cell growth inhibition rate by flow cytometry and apoptosis index by TUNEL staining. The protein expression of p53, Bcl-2, Bax, and caspase-3 were analyzed by Western blot. RESULTS Flow cytometry results showed that BRP inhibited Hep2 cell proliferation in a dose-dependent manner (p<0.05), and TUNEL staining indicated that BRP significantly increased Hep2 apoptosis index (p<0.05). Western blot results showed that the expression levels of p53 and activation of caspase-3 in Hep2 cells were significantly up-regulated (p<0.05), while the expression of Bcl-2 was significantly down-regulated (p<0.05). CONCLUSIONS BRP might induce cell apoptosis by regulating the expression level of cell apoptosis-associated proteins, suggesting strong anti-laryngeal cancer activity.

miR-199a-5p regulates ß1 integrin through Ets-1 to suppress invasion in breast cancer.

Increasing evidence has revealed that miR-199a-5p is actively involved in tumor invasion and metastasis as well as in the decline of breast cancer tissues. In this research, overexpression of miR-199a-5p weakened motility and invasion of breast cancer cells MCF-7 and MDA-MB-231. Upregulation of Ets-1 increased breast cancer cell invasion, but the mechanism by which miR-199a-5p modulates activation of Ets-1 in breast cancer was not clarified. We investigated the relationship between miR-199a-5p and Ets-1 on the basis of 158 primary breast cancer case specimens, and the results showed that Ets-1 expression was inversely correlated with endogenous miR-199a-5p. Overexpression of miR-199a-5p reduced the mRNA and protein levels of Ets-1 in MCF-7 and MDA-MB-231 cells, whereas anti-miR-199a-5p elevated Ets-1. siRNA-mediated Ets-1 knockdown phenocopied the inhibition invasion of miR-199a-5p in vitro. Moreover, luciferase reporter assay revealed that miR-199a-5p directly targeted 3'-UTR of Ets-1 mRNA. This research revealed that miR-199a-5p could descend the levels of ß1 integrin by targeting 3'-UTR of Ets-1 to alleviate the invasion of breast cancer via FAK/Src/Akt/mTOR signaling pathway. Our results provide insight into the regulation of ß1 integrin through miR-199a-5p-mediated Ets-1 silence and will help in designing new therapeutic strategies to inhibit signal pathways induced by miR-199a-5p in breast cancer invasion.

miR-143 suppresses epithelial-mesenchymal transition and inhibits tumor growth of breast cancer through down-regulation of ERK5.

Epithelial-mesenchymal transition (EMT) plays a pivotal role in the development of cancer invasion and metastasis. Many studies have significantly enhanced the knowledge on EMT through the characterization of microRNAs (miRNAs) influencing the signaling pathways and downstream events that define EMT on a molecular level. In this study, we found that miR-143 suppressed EMT. Up-regulating miR-143 enhanced E-cadherin-mediated cell-cell adhesion ability, reduced mesenchymal markers, and decreased cell proliferation, migration, and invasion in vitro. In vivo, the xenograft mouse model also unveiled the suppressive effects of miR-143 on tumor growth. Additionally, we demonstrated that up-regulating extracellular signal regulated kinase 5 (ERK5) was associated with poor prognosis of breast cancer patients. Moreover, we observed an inverse correlation between miR-143 and ERK5 in breast cancer tissues. miR-143 directly targeted seed sequences in the 3'-untranslated regions of ERK5. Furthermore, we revealed that the downstream molecules of glycogen synthase kinase 3 beta (GSK-3ß)/Snail signaling were involved in EMT and modulated by ERK5. In summary, our findings demonstrated that miR-143 down-regulated its target ERK5, leading to the suppression of EMT induced by GSK-3ß/Snail signaling of breast cancer. © 2015 Wiley Periodicals, Inc.

MiR-153 inhibits epithelial-mesenchymal transition by targeting metadherin in human breast cancer.

Epithelial-mesenchymal transition (EMT) is a crucial step in epithelial cancer invasion and metastasis. miR-153 has been identified as a key EMT suppressor. Accordingly, this study aimed to determine the possible relation of miR-153 downregulation to EMT through MTDH modulation. The miR-153 and MTDH expression profiles of human breast cancer specimen were determined by qPCR and evaluated by correlation analysis. Cell viability and clonogenic assays were applied to explore the impact of miR-153 on suppression of proliferation and oncogenic potential of breast cancer cells. Cell migration and invasion assays were used for the functional analysis of miR-153 in MCF-7 and MDA-MB-231 cells. Luciferase assay was adopted to identify MTDH as a new direct target of miR-153. Ectopic expression of miR-153 could significantly inhibit tumor growth and impair the migration and invasion of breast cancer cells. Overexpression of miR-153 simultaneously increased E-cadherin, decreased vimentin expression, and downmodulated EMT-associated transcription factors. miR-153 was negatively correlated with MTDH in cell lines and clinical samples. Overexpression of miR-153 significantly suppressed MTDH, as demonstrated by in vitro MTDH 3'-untranslated region luciferase report assay. MTDH is a direct downstream target of miR-153 and is involved in the miR-153-induced suppression of the migration and invasion of breast cancer cells. Our findings indicate that miR-153 functions as a tumor suppressor and miR-153/MTDH link is a promising therapeutic target for breast cancer.

[Protective effects of metformin on glomerular podocytes of type 2 diabetes model rats].

OBJECTIVE: To observe the effects of metformin (MET) on podocalyxin (PCX) expression in renal tissue from type 2 diabetes mellitus (T2DM) model rats and investigate its protective effects against glomerular podocyte injury. METHOD: The rat model of T2DM was established by feeding with high-fat diet and intraperitoneal injection of low dose of streptozotocin (STZ). All the rats were divided into four groups: diabetic group (n=9), metformin group (300 mg·kg(-1)·d(-1), n=8), glibenclamide group (5 mg·kg(-1)·d(-1), n=8 ) and normal group (n=8). After 8 weeks, urinary PCX and creatinine, blood glucose (BG) and glycated hemoglobin (HbA1c) were detected in all the rats. Immunohistochemistry was used to observe the protein expression of PCX in renal tissue. Real-time polymerase chain reaction (PCR) was performed to detect mRNA expression of PCX. Pathological changes of renal tissue were observed by electron microscope. RESULTS: Metformin and glyburide treatment decreased the levels of BG and HbA1c [(9.6±1.1) and (9.9±1.1) vs (15.6±1.6) mmol/L, (7.0±0.3)% and (8.0±1.0)% vs (12.4±0.6)%, all P<0.05], compared with diabetes group, while there was no statistically significant difference between the two intervention groups (P>0.05). The level of urinary PCX/urinary creatinine (UPCR) in diabetic rats were higher than that of normal group [(697±136) vs (94±25 ) ng/g, P<0.05), meanwhile the levels of protein and mRNA expression of PCX in kidney tissue reduced remarkably [(0.75±0.11) vs (3.18±0.14), (0.08±0.09) vs (1.00±0.02), both P<0.05]. Above-mentioned indicators could be ameliorated by metformin and glyburide treatment compared to normal group (P<0.05), and there were statistically significant difference between the two intervention groups [(404±83) vs (516±38) ng/g, (1.54±0.06) vs(1.06±0.10), (0.23±0.01) vs (0.16±0.04), all P<0.05)]. Further observation found that basement membrane thickness of kidney [(267±22) vs (106±10)nm )] and fusion rate of foot process (0.80±0.07 vs 0) increased in the rats of diabetic group, and metformin or glyburide treatment can significantly reduced the above changes (P<0.05), additionally, the changes were remarkable different between metformin and glyburide group [(151±17) vs (204±22 ) nm, (0.49±0.04) vs (0.57±0.03), both P<0.05)]. CONCLUSION: Metformin has protective effect on glomerular podocytes by regulating the expression of PCX in renal tissue, independent of its hypoglycemic effect.

Coffee consumption and prostate cancer risk: an updated meta-analysis.

PURPOSE: Many epidemiological studies have been conducted to explore the association between coffee consumption and prostate cancer. However, the results remain inconsistent. We performed a large meta-analysis of relevant studies to derive a more precise estimation of this relationship. METHODS: Systematic searches of PubMed and several other databases up to June 2013 were retrieved. All epidemiologic studies regarding coffee consumption and prostate cancer risk were included, and odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to estimate the strength of the association. RESULTS: Twelve case-control studies involving 7,909 prostate cancer cases and 9,461 controls and nine cohort studies involving 455,123 subjects were included in our analysis. Compared with the lowest category, the unstratified highest category of coffee consumption showed a significance reduction in prostate cancer risk of a fixed-effects model (OR 0.91, CI 0.86-0.97). A borderline significant influence was also found when the stratified highest category (US ≥ 4, Europe ≥ 5) of coffee consumption was compared with the reference category (OR 0.96, CI 0.92-1.00), but no relationships were observed for the other two categories. In another analysis conducted by coffee consumption and prostate cancer stage and Gleason grade, our results showed a significant inverse association in all categories of prostate cancer except Gleason <7 grade in a fixed-effects model; the results remained the same, except for advanced prostate cancer, in a random-effects model. CONCLUSIONS: Our meta-analysis suggests that high (e.g., highest ≥ 4 or 5 cups/day) coffee consumption may not only be associated with a reduced risk of overall prostate cancer, but also inversely associated with fatal and high-grade prostate cancer.

DNA repair gene XRCC3 polymorphisms and bladder cancer risk: a meta-analysis.

The X-ray repair cross-complementing group 3 (XRCC3) in homologous recombination repair (HRR) pathway plays a vital role in DNA double-strand break repair (DSBR). Variants in the XRCC3 gene might result in altered protein structure or function which may influence DSBR efficiency and lead to cancer. Numerous epidemiological studies have been conducted to evaluate the association between XRCC3 polymorphisms and bladder cancer risk. However, the results of these previous studies have been inconsistent. To derive a more precise estimation of the association, we performed a meta-analysis of all available studies relating XRCC3 polymorphisms and bladder cancer. All studies published up to April 2013 on the association between XRCC3 polymorphisms and bladder cancer risk were identified by searching electronic databases PubMed, EMBASE, and Chinese Biomedical Literature databases. The association between the XRCC3 polymorphisms and bladder cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). A total of 16 case-control studies met the inclusion criteria and were selected. With respect to C18067T polymorphism, significant increased bladder cancer risk was found when all eligible studies were pooled into the meta-analysis (TT vs. CC: OR = 1.174, 95%CI = 1.033-1.335, P = 0.014 and recessive model TT vs. TC + CC: OR = 1.147, 95%CI = 1.020-1.290, P = 0.022, respectively). The results were still significant after excluding the Hardy-Weinberg equilibrium violation studies (TT vs. CC: OR = 1.178, 95%CI = 1.036-1.339, P = 0.013 and recessive model TT vs. TC + CC: OR = 1.144, 95%CI = 1.017-1.287, P = 0.025, respectively). In subgroup analysis by ethnicity, significant elevated risk was found among Asians (dominant model TT + TC vs. CC: OR = 1.285, 95%CI = 1.012-1.631). In the subgroup analyses according to smoking status, no significant association was detected in all genetic comparison models. With respect to A17893G and A4541G polymorphisms, no significant association with bladder cancer risk was observed in the overall and subgroup analyses. This meta-analysis suggests that the XRCC3 C18067T polymorphism was associated with increased bladder cancer risk especially among Asians. However, the XRCC3 A17893G and A4541G polymorphisms may not play important roles in bladder carcinogenesis. Further studies with larger sample sizes are needed to validate our finds.

Meta-analysis: eating frequency and risk of colorectal cancer.

Eating frequency has been implicated in the risk of colorectal cancer (CRC) in several epidemiological studies with contradictory and inconclusive findings. We performed a meta-analysis to evaluate their relationship. The pooled relative risk (RR) with 95% confidence interval (CI) was calculated to estimate the effects. A total of 15 eligible studies with 141,431 subjects and 11,248 cases were retrieved after a comprehensive search of the PubMed, Cochrane Library, and Web of Science databases up to October 2013. The overall meta-analysis revealed no strong significant association between eating frequency and risk of CRC in different eating occasion categories (1 meal/day): RR = 1.01, 95% CI 0.94-1.09, P = 0.709; 3 vs. <3 daily meals: RR = 1.17, 95% CI 0.93-1.46; 4 vs. <3 daily meals: RR = 1.13, 95% CI 0.92-1.38; ≥ 5 vs. <3 daily meals: RR = 0.95, 95% CI 0.61-1.47; 4 vs. ≤ 3 daily meals: RR = 1.18, 95% CI 0.92-1.51; and 1-2 vs. 3 or 4 daily meals: RR = 0.82, 95% CI 0.63-1.06). However, modest evidence of an increased risk of CRC in case-control studies (RR = 1.30; 95% CI, 1.11-1.52) and ≥ 5 vs. ≤ 3 meals group (RR = 1.30; 95% CI, 1.11-1.52) was observed. Our meta-analysis results do not support the hypothesis that eating frequency strongly reduced or increased the risk of CRC. Clinical randomized trials are required to evaluate this relationship further.

Prognostic significance of dickkopf-1 overexpression in solid tumors: a meta-analysis.

The prognostic significance of dickkopf-1 (DKK1) overexpression in solid tumors remains inconclusive. We performed a meta-analysis to evaluate the impact of DKK1 overexpression in solid tumors on patients' overall survival (OS) and disease-free survival (DFS). The pooled hazard ratio (HR) with 95 % confidence interval (CI) was used to estimate the effects. Thirteen studies were included for meta-analysis; four that evaluated hepatocellular carcinoma (HCC), two each that evaluated ovarian carcinoma, esophageal carcinoma, and lung cancer, and one each that evaluated other cancers, namely gastric cancer, breast cancer, urothelial carcinoma, and colorectal cancer. Twelve studies were evaluable for OS and six for DFS. Our analysis results indicated that DKK1 overexpression predicted poor OS (HR = 1.68, 95% CI 1.36-2.08; P < 0.001) and DFS (HR = 1.65, 95% CI 1.37-1.99; P < 0.001). Subgroup analyses showed that DKK1 overexpression was significantly related with poor OS in HCC patients (HR = 1.65; P < 0.001), ovarian carcinoma patients (HR = 2.63; P = 0.045), and other cancers patients (HR = 1.51; P = 0.021). Further, DKK1 overexpression was significantly related with poor DFS in HCC patients (HR = 1.53; P < 0.001) and other cancers patients (HR = 2.02; P < 0.001). This meta-analysis showed that DKK1 may be a novel prognostic marker in solid tumors in Asian patients; it could potentially help to further stratify patients for clinical treatment. More, well-designed studies from Western countries are needed to confirm this finding.

The association of interleukin-16 gene polymorphisms with IL-16 serum levels and risk of nasopharyngeal carcinoma in a Chinese population.

Interleukin (IL)-16 plays a fundamental role in inflammatory diseases, as well as in the development and progression of tumors. Genetic variation in DNA sequence of IL16 gene may lead to altered cytokine production and/or activity, and this variation may modulate an individual's susceptibility to nasopharyngeal carcinoma (NPC). To test this hypothesis, we investigated the association of IL16 gene polymorphisms and serum IL-16 levels with NPC risk in a Chinese population. We analyzed IL16 gene rs11556218 T/G, rs4778889 T/C, and rs4072111 C/T polymorphisms using PCR-RFLP and DNA sequencing, and serum IL-16 levels were measured by ELISA. The IL16 rs11556218 T/G polymorphism was significantly associated with the susceptibility to NPC patients. The TG genotype was associated with a significantly higher risk of NPC as compared with the TT genotype (OR = 2.05, 95% CI 1.04-4.01; p = 0.037). Patients carrying the G allele had a significantly higher risk for developing NPC compared with individuals carrying the T allele (OR = 1.79, 95% CI 1.07-3.01; p = 0.027). The serum IL-16 levels were increased in NPC patients compared with controls (p < 0.01); the genotypes carrying the IL16 rs11556218 G variant allele were associated with increased serum IL-16 levels compared with the homozygous wild-type genotype in NPC patients (all p values <0.01). Our data suggested that IL16 rs11556218 T/G polymorphism was associated with increased susceptibility to NPC through increasing the production of serum IL-16 levels.

Determination of reference intervals for serum complement C3 and C4 levels in Chinese Han ethnic males.

BACKGROUND: Clinical laboratory reference intervals (RIs) for serum complement C3 and C4 levels have been established in many countries but there is a lack of published data regarding normal RIs in Chinese population. We attempted to establish RIs for serum complement C3 and C4 levels in Chinese Han ethnic males. METHODS: A total of 1,234 healthy male subjects, aged 20 - 69 years, were collected from the Fangchenggang Area Male Health and Examination Survey (FAMHES). Serum complement C3 and C4 levels were measured by immunoturbidimetry. The two-sided 95-percentile RIs were calculated using parametric statistical methods. RESULTS: Serum C3 values showed normal distribution and C4 were log-normal distributed. The two-sided 95% RIs (mean +/- 2 SD) for serum C3 and C4 were 0.656 - 1.52 g/L and 0.181 - 0.561 g/L, respectively. Body Mass Index (BMI) had a significant positive association with C3 (r = 0.342) and C4 (r = 0.258), and age had a significant positive association with C4 (r = 0.117). No significant difference was found either between smoking groups or drinking groups. A significant increase with BMI was found both for C3 (p < 0.001) and C4 (p < 0.001). BMI-specific RIs were also calculated. CONCLUSIONS: The RIs for serum C3 and C4 show a slight deviation compared to previously reported reference levels. BMI-specific reference values should be implemented in clinical laboratories.

Lack of association between LUM rs3759223 polymorphism and high myopia.

PURPOSE: Previous evidence has indicated that the lumican (LUM) gene is a candidate susceptibility gene of high myopia; however, the association between LUM promoter regions rs3759223 polymorphism and high myopia remains controversial and ambiguous. This study performed a meta-analysis to clarify the association between the rs3759223 polymorphism and high myopia risk. METHODS: Eligible studies were identified by comprehensive search of PubMed, EMBASE, Web of Science, and Chinese Biomedical Literature database. The crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were used to estimate the association between the rs3759223 polymorphism and high myopia susceptibility. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. RESULTS: Finally, six studies including 1238 cases and 1059 healthy controls were included. Meta-analyses showed no association between rs3759223 polymorphism and high myopia susceptibility in all genetic models (CC vs. TT, OR = 1.089; 95% CI, 0.690 to 1.718; CT vs. TT, OR = 0.865; 95% CI, 0.646 to 1.157; CC + CT vs. TT, OR = 1.202; 95% CI, 0.730 to 1.980; CC vs. CT + TT, OR = 0.914; 95% CI, 0.771 to 1.083) and no significance in subgroup analyses according to the definition of high myopia (based on more myopic than -6.00 diopters vs. not based on more myopic than -6.00 diopters). Publication bias was not evident in this study. CONCLUSIONS: This meta-analysis has suggested that there is a lack of association of the rs3759223 polymorphism with high myopia risk. However, further large and well-designed studies with the consideration of LUM gene locus interactions and gene-gene and gene-environment interactions are still required to further evaluate high myopia risk.

[Retracted] MicroRNA­671­5p inhibits cell proliferation, migration and invasion in non­small cell lung cancer by targeting MFAP3L.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the western blotting data shown in Fig. 4B and the Transwell cell invasion data shown in Figs. 2D and 4E were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had already been published elsewhere prior to the submission of this paper to Molecular Medicine Reports (one of which has been retracted). Moreover, there appeared to be inappropriately edited western blot bands featured in Figs. 4 and 5. In view of the fact that certain of the abovementioned data had already apparently been published previously, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 25: 30, 2022; DOI: 10.3892/mmr.2021.12546].

Focused ultrasound-mediated cerium-based nanoreactor against Parkinson's disease via ROS regulation and microglia polarization.

Neuronal damage caused by oxidative stress and inflammatory microenvironment dominated by microglia are the main obstacles in the treatment of Parkinson's disease (PD). In this study, we developed an integrated nanoreactor Q@CeBG by encapsulating CeO2 nanozyme and quercetin (Que) into glutathione-modified bovine serum albumin, and then selected focused ultrasound (FUS) to temporarily open the blood-brain barrier (BBB) to enhance the accumulation level of Q@CeBG in the brain. Q@CeBG exhibited superior multi-ROS scavenging activity. Under the assistance of FUS, Q@CeBG nanoreactor can penetrate the BBB and act on neurons as well as microglia, reducing the neuron's oxidative stress level and polarizing microglia's phenotype from proinflammatory M1 to anti-inflammatory M2. In vitro and In vivo experiments demonstrated that Q@CeBG nanoreactor with good biocompatibility exhibit outstanding neuroprotection and immunomodulatory effects. In short, this dual synergetic nanoreactor will become a reliable platform against PD.

Finotonlimab with chemotherapy in recurrent or metastatic head and neck cancer: a randomized phase 3 trial.

Immunotherapy combined with chemotherapy regimen has been shown to be effective in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, due to the small number of patients, its efficacy remains controversial in Asian populations, particularly in mainland China. Here a randomized, double-blind phase 3 trial evaluated the efficacy and safety of finotonlimab (SCT-I10A), a programmed cell death 1 (PD-1) monoclonal antibody, combined with cisplatin plus 5-fluorouracil (C5F) for the first-line treatment of R/M HNSCC. Eligible patients (n = 370) were randomly 2:1 assigned to receive finotonlimab plus C5F (n = 247) or placebo plus C5F (n = 123). The primary endpoint was overall survival (OS). In the finotonlimab plus C5F group, OS was 14.1 months (95% confidence interval (CI) 11.1-16.4), compared with 10.5 months (95% CI 8.1-11.8) in the placebo plus C5F group. The hazard ratio was 0.73 (95% CI 0.57-0.95, P = 0.0165), meeting the predefined superiority criteria for the primary endpoint. Finotonlimab plus C5F showed significant OS superiority compared with C5F alone and acceptable safety profile with R/M HNSCC, supporting its use as a first-line treatment option for R/M HNSCC. These results validate the efficacy and safety of the combination of finotonlimab and C5F in Asian patients with R/M HNSCC. ClinicalTrials.gov identifier: NCT04146402 .

Preparation of injectable porcine skin-derived collagen and its application in delaying skin aging by promoting the adhesion and chemotaxis of skin fibroblasts.

Collagen, as the main component of human skin, plays a vital role in maintaining dermal integrity. Its loss will lead to dermis destruction and collapse, resulting in skin aging. At present, injection of exogenous collagen is an important means to delay skin aging. In this study, high-purity collagen was extracted from porcine skin. Our research revealed that it can effectively promote the adhesion and chemotaxis of HSF cells. It can also reduce the expression of ß-galactosidase, decrease ROS levels, and increase the expression of the collagen precursors, p53 and p16 in HSF cells during senescence. After local injection into the aging skin of rats, it was found that the number of cells and type I collagen fibers in the dermis increased significantly, and the arrangement of these fibers became more uniform and orderly. Moreover, the important thing is that it is biocompatible. To sum up, the porcine skin collagen we extracted is an anti-aging biomaterial with application potential.

Efficacy and safety of KL-A167 in previously treated recurrent or metastatic nasopharyngeal carcinoma: a multicenter, single-arm, phase 2 study.

Background: KL-A167 is a fully humanized monoclonal antibody targeting programmed cell death-ligand 1. This phase 2 study aimed to evaluate the efficacy and safety of KL-A167 in Chinese patients with previously treated recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC). Methods: This was a multicentre, single-arm, phase 2 study of KL-A167 in R/M NPC (KL167-2-05-CTP) (NCT03848286), conducted at 42 hospitals across the People's Republic of China. Eligible patients had histologically confirmed non-keratinising R/M NPC, and had failed at least two lines of chemotherapy. Patients received KL-A167 900mg intravenously once every 2 weeks until confirmed disease progression, intolerable toxicity, or withdrawal of informed consent. The primary endpoint was objective response rate (ORR) assessed by the independent review committee (IRC) according to RECIST v1.1. Findings: Between Feb 26th, 2019 and Jan 13th, 2021, 153 patients were treated. Totally, 132 patients entered full analysis set (FAS) and were evaluated for the efficacy. As of data cutoff date on Jul 13th, 2021, the median follow-up time was 21.7 months (95%CI 19.8-22.5). For FAS population, the IRC-assessed ORR was 26.5% (95%CI 19.2-34.9%), and disease control rate (DCR) was 56.8% (95%CI 47.9-65.4%). Median progression-free survival (PFS) was 2.8 months (95%CI 1.5-4.1) . Median duration of response was 12.4 months (95%CI 6.8-16.5), and median overall survival (OS) was 16.2 months (95%CI 13.4-21.3). When using the cutoff of 1000 copies/ml, 5000 copies/ml and 10,000 copies/ml for plasma EBV DNA titer, baseline low plasma EBV DNA was consistently related with better DCR, PFS and OS. Dynamic change of plasma EBV DNA was significantly associated with ORR and PFS. Among 153 patients, treatment related-adverse events (TRAEs) occurred in 73.2% of patients, and grade ≥3 TRAEs were in 15.0% of patients. No TRAE leading to death was reported. Conclusion: In this study, KL-A167 showed promising efficacy and an acceptable safety profile in patients with previously treated R/M NPC. Baseline plasma EBV DNA copy number might be a potentially useful prognostic biomarker for KL-A167 treatment, and post-treatment EBV DNA decrease might be correlated with better response to KL-A167. Funding: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd., China National Major Project for New Drug Innovation (2017ZX09304015).