Prognostic value of maximum standard uptake value, metabolic tumour volume, and total lesion glycolysis of 18F-FDG PET/CT in patients with malignant pleural mesothelioma: a systematic review and meta-analysis.

PURPOSE: Present work systematically reviewed relevant literature based on 18F-FDG PET parameters and conducted a meta-analysis to examine the prognostic value of maximal standard uptake value (SUVmax), total lesional glycolysis (TLG), and metabolic tumour volume (MTV) in the prognosis of malignant pleural mesothelioma (MPM). METHODS: The relevant literature published in English were searched on PubMed, Cochrane Library, and EMBASE databases. We also evaluated the significance of SUVmax, TLG, and MTV in prognosis prediction using pooled hazard ratios (HRs). RESULTS: The current study comprised 12 primary studies with a total of 1307 MPM cases. According to our results, the pooled HR (95% confidence interval [CI]) of increased SUVmax for overall survival (OS) was 1.30 (95% CI 1.13-1.49, P = 0.000), whereas the increased TLG was 1.81(95% CI 1.25-2.61, P = 0.089). The increased MTV was not significantly related to OS (1.14 [95% CI 0.87-1.50, P = 0.18]).However, study design-stratified subgroup analysis suggested that differences in OS of retrospective and prospective subgroups were statistically significant, and no significant heterogeneity among different studies was observed. CONCLUSION: Based on the findings from the present work, PET/CT can significantly affect the prognosis prediction in MPM cases. Also, the increased SUVmax and TLG values predict an increased risk of mortality.

ERBB3 binding protein 1 promotes the progression of malignant melanoma through activation of the Wnt/ ß-catenin signaling pathway.

BACKGROUND: Malignant melanoma (MM) is highly metastatic and has the highest mortality rate in patients with skin cancer. The ERBB3 binding protein 1 (Ebp1) has been linked to the onset and progression of a number of malignancies. However, the role of Ebp1 in MM has not yet been reported. METHODS: Multiple databases were analyzed for comparing the expression of Ebp1 in normal skin and MM. Ebp1 expression was knocked down in A375 and B16 cells, and the impact of Ebp1 on the cell growth was tested by CCK-8, plate clone colony, and cell cycle assays. Scratch, transwell, and in vivo caudal vein lung metastasis tests were also used to confirm the effects of Ebp1 on melanoma cells migration, invasion, and metastasis. Furthermore, the possible molecular mechanism of Ebp1 was predicted by set enrichment analysis and verified by western blotting. RESULTS: Ebp1 expression was substantially higher in MM than it was in normal skin, and Ebp1 was linked to the clinical stage and lymph node metastases of patients with MM. Knockdown of Ebp1 inhibited cell proliferation, migration, and invasion. In vivo experiments further verified that the knockdown of Ebp1 had an obvious inhibitory effect on lung metastasis in nude mice. Knockdown of Ebp1 reduced vimentin, N-cadherin, slug, and snail expression while increasing E-cadherin expression. Furthermore, knockdown of Ebp1 reduced the expression of ß-catenin, as well as its downstream targets CyclinD1 and p-GSK3ß; however, a Wnt/ß-catenin agonist could reverse this effect. CONCLUSION: Ebp1 may promote the proliferation and metastasis of melanoma cells through activation of the Wnt/ß-catenin pathway.

Binding-Induced Fibrillogenesis Peptides Recognize and Block Intracellular Vimentin Skeletonization against Breast Cancer.

Life is recognized as a sophisticated self-assembling material system. Cancer involves the overexpression and improper self-assembly of proteins, such as cytoskeleton protein vimentin, an emerging target related to tumor metastasis. Herein, we design a binding-induced fibrillogenesis (BIF) peptide that in situ forms fibrous networks, blocking the improper self-assembly of vimentin against cancer. The BIF peptide can bind to vimentin and subsequently perform fibrillogenesis to form fibers on vimentin. The resultant peptide fibrous network blocks vimentin skeletonization and inhibits the migration and invasion of tumor cells. In mouse models of tumor metastasis, the volume of tumor and the number of lung metastases are markedly decreased. Moreover, the efficacy of BIF peptide (5 mg/kg) is much higher than small molecular antimetastasis drug withaferin A (5 mg/kg) as a standard, indicating that the BIF peptide shows advantages over small molecular inhibitors in blocking the intracellular protein self-assembly.

Ebp1 p48 promotes oncogenic properties in hepatocellular carcinoma through p38 MAPK/HIF1α activation and p53 downregulation.

The ErbB3 binding protein 1 (Ebp1) has been reported in several cancers, in which it can act as either a pro-oncogenic regulator or a tumor suppressor. However, the biological function and molecular mechanism of Ebp1 p48 in hepatocellular carcinoma (HCC) remain unclear. Here, we report that the long isoform of Ebp1, p48, is highly expressed in HCC tissues compared with normal tissues. Ebp1 p48 expression was correlated with the tumor size in HCC patients. Silencing Ebp1 p48 by transduction with lentiviral shEbp1 dramatically reduced the proliferation rate, soft agar colony generation, and tumor formation in vivo. We further demonstrated that Ebp1 p48 knockdown resulted in decreased p38 phosphorylation, which subsequently reduced hypoxia-inducible factor 1α (HIF1α) expression. Moreover, Ebp1 p48 knockdown led to an upregulation of p53 expression through MDM2 downregulation. Taken together, these results suggest that the Ebp1/p38/HIF1α signaling pathway and the Ebp1-mediated downregulation of p53 are involved in hepatocarcinogenesis. Therefore, Ebp1 and its downstream signaling pathways may be promising therapeutic targets of HCC.

Paeoniflorin ameliorates neuropathic pain-induced depression-like behaviors in mice by inhibiting hippocampal neuroinflammation activated via TLR4/NF-κB pathway.

Neuropathic pain (NP) that contributes to the comorbidity between pain and depression is a clinical dilemma. Neuroinflammatory responses are known to have potentially important roles in the initiation of NP and depressive mood. In this study, we aimed to investigate the effects of paeoniflorin (PF) on NP-induced depression-like behaviors by targeting the hippocampal neuroinflammation through the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. We used a murine model of NP caused by unilateral sciatic nerve cuffing (Cuff ). PF was injected intraperitoneally once a day for a total of 14 days. Pain and depression-like behavior changes were evaluated via behavioral tests. Pathological changes in the hippocampus of mice were observed by H&E staining. The levels of proinflammatory cytokines in the hippocampus were detected using ELISA. Activated microglia were measured by immunohistochemical staining. The TLR4/NF-κB signaling pathwayassociated protein expression in the hippocampus was detected by western blotting. We found that the PF could significantly alleviate Cuff-induced hyperalgesia and depressive behaviors, lessen the pathological damage to the hippocampal cell, reduce proinflammatory cytokines levels, and inhibit microglial over-activation. Furthermore, PF downregulated the expression levels of TLR4/NF-κB signaling pathwayrelated proteins in the hippocampus. These results indicate that PF is an effective drug for improving the comorbidity between NP and depression.

Bispyrene-Based Self-Assembled Nanomaterials: In Vivo Self-Assembly, Transformation, and Biomedical Effects.

Self-assembled nanomaterials show potential high efficiency as theranostic agents for high-performance imaging and therapy. However, superstructures and properties of preassembled nanomaterials are somewhat compromised under complicated physiological conditions. Given the advantages of the dynamic nature and adaptive behavior of self-assembly systems, we propose an "in vivo self-assembly" strategy for in situ construction of nanomaterials in living objects. For the proof-of-concept study of in vivo self-assembly, we developed a bispyrene (BP) molecule as a multifunctional building block. BP molecules show nonfluorescence in the monomeric state. Quantum-chemical calculations indicate that BP forms twisted intramolecular charge transfer states, which are separated into two orthogonal units, preventing the fluorescence emission. Interestingly, the typical excimeric emission of BP is observed with the formation of J-type aggregates, as confirmed by single-crystal X-ray diffraction. Packing of the BP molecules generates parallel pyrene units that interact with adjacent ones in a slipped face-to-face fashion through intermolecular π-π interactions. BP and/or its amphiphilic derivatives are capable of self-aggregating into nanoparticles (NPs) in aqueous solution because of the hydrophobic and π-π interactions of BP. Upon specific biological stimuli, BP NPs can be transformed into variable self-assembled superstructures. Importantly, the self-assembled BP NPs exhibit turn-on fluorescence signals that can be used to monitor the self-assembly/disassembly process in vitro and in vivo. On the basis of the photophysical properties of BP and its aggregates, we synthesized a series of designed BP derivatives as building blocks for in situ construction of functional nanomaterials for bioimaging and/or therapeutics. We observed several new biomedical effects, e.g., (i) the assembly/aggregation-induced retention (AIR) effect, which shows improved accumulation and retention of bioactive nanomaterials in the regions of interests; (ii) the transformation-induced surface adhesion (TISA) effect, which means the BP NPs transform into nanofibers (NFs) on cell surfaces upon binding with specific receptors, which leads to less uptake of BP NPs by cells via traditional endocytosis pathway; and (iii) transformation of the BP NPs into NFs in the tumor microenvironment, showing high accumulation and long-term retention, revealing the transformation-enhanced accumulation and retention (TEAR) effect. In this Account, we summarize the fluorescence property and emission mechanism of BP building blocks upon aggregation in the biological environment. Moreover, BP-derived compounds used for in vivo self-assembly and transformation are introduced involving modulation strategies. Subsequently, unexpected biomedical effects and applications for theranostics of BP based nanomaterials are discussed. We finally conclude with an outlook toward future developments of BP-based self-assembled nanomaterials.

Sesamin induces A549 cell mitophagy and mitochondrial apoptosis via a reactive oxygen species-mediated reduction in mitochondrial membrane potential.

Sesamin, a lipid-soluble lignin originally isolated from sesame seeds, which induces cancer cell apoptosis and autophagy. In the present study, has been reported that sesamin induces apoptosis via several pathways in human lung cancer cells. However, whether mitophagy is involved in sesamin induced lung cancer cell apotosis remains unclear. This study, the anticancer activity of sesamin in lung cancer was studied by reactive oxygen species (ROS) and mitophagy. A549 cells were treated with sesamin, and cell viability, migration ability, and cell cycle were assessed using the CCK8 assay, scratch-wound test, and flow cytometry, respectively. ROS levels, mitochondrial membrane potential, and apoptosis were examined by flow cytometric detection of DCFH-DA fluorescence and by using JC-1 and TUNEL assays. The results indicated that sesamin treatment inhibited the cell viability and migration ability of A549 cells and induced G0/G1 phase arrest. Furthermore, sesamin induced an increase in ROS levels, a reduction in mitochondrial membrane potential, and apoptosis accompanied by an increase in cleaved caspase-3 and cleaved caspase-9. Additionally, sesamin triggered mitophagy and increased the expression of PINK1 and translocation of Parkin from the cytoplasm to the mitochondria. However, the antioxidant N-acetyl-L-cysteine clearly reduced the oxidative stress and mitophagy induced by sesamin. Furthermore, we found that cyclosporine A (an inhibitor of mitophagy) decreased the inhibitory effect of sesamin on A549 cell viability. Collectively, our data indicate that sesamin exerts lethal effects on lung cancer cells through the induction of ROS-mediated mitophagy and mitochondrial apoptosis.

LncRNA FTX inhibits hippocampal neuron apoptosis by regulating miR-21-5p/SOX7 axis in a rat model of temporal lobe epilepsy.

Emerging evidence has shown that long noncoding RNA (LncRNA) is involved in the development of epileptogenesis. However, the expression profile and the biological function of FTX in epilepsy remains unclear. This study aimed to provide functional evidence and elucidate the molecular mechanisms by which the FTX affects status epilepticus (SE) induced hippocampal apoptosis. SE rat model was introduced by intraperitoneal injection of lithium chloride and pilocarpine. Our results showed that FTX is notably reduced in the hippocampus. Moreover, the in vivo overexpression of FTX inhibited SE-induced hippocampus neuron apoptosis. Mechanically, we found that FTX negatively regulated miR-21-5p expression by targeting its 3'UTR to regulate neuron apoptosis. Upregulation of miR-21-5p attenuates anti-apoptosis property of FTX overexpression by regulating SOX7 expression in epileptiform hippocampal neurons. Collectively, our study for the first time demonstrated the anti-apoptosis ability of FTX during epileptogenesis and uncovered a novel FTX-mediated mechanism in SE-induced neural apoptosis by targeting miR-21-5p/SOX7 axis, which provides a new target in developing lncRNA-based strategies to reduce SE-induced hippocampal neuron apoptosis.

RILPL2 is associated with the progression and prognosis of cervical squamous cell carcinoma and endocervical adenocarcinoma.

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is one of the most common tumors among females worldwide. RILPL2 was recently reported to be a promising biomarker for the treatment of breast cancer. This study aimed to investigate the potential role of RILPL2 in CESC. Totally 302 CESC patients' data were downloaded from The Cancer Genome Atlas database. All patients were divided into high or low RILPL2 groups according to the median expression of RILPL2. Subsequently, survival analysis, multivariate Cox regression, and experimental validation were performed on all CESC patient data. The Ualcan database was used to analyze the expression level and prognostic value of RILPL2 in pan-cancer. The Gene Set Cancer Analysis database was used for drug sensitivity analysis. Functional KEGG pathways were analyzed using gene set enrichment analysis. RILPL2 was generally down-regulated in a variety of tumors, and a high level of RILPL2 was associated with a better prognosis in CESC patients. Immunohistochemistry, western blotting, and qRT-PCR results showed that RILPL2 was significantly down-regulated in CESC cells and tissues. Besides, along with the increase of TNM Stage, the RILPL2 expression tended to decrease gradually. Patients with high RILPL2 expression showed lower resistance to small molecule drugs used in CESC progressions, such as Methotrexate, AZD7762, and Vinblastine, and a higher response rate to immunotherapy. Additionally, we identified 267 co-expressing genes of RILPL2, all of which jointly affected CESC progression through 15 complex pathways. Low RILPL2 expression was closely associated with the onset, progression, and poor prognosis of CESC. RILPL2 might be a promising optional biomarker for CESC patients' diagnosis and prognosis.

Prognostic value of lymphovascular space invasion in stage IA to IIB cervical cancer: A meta-analysis.

BACKGROUND: Lymphovascular space invasion (LVSI) is a prognostic factor in the existing TNM classification system. The present meta-analysis assessed the role of LVSI in predicting the prognosis of stage IA to IIB cervical cancer (CC). MATERIALS AND METHODS: PubMed, EMBASE, and Cochrane Library electronic databases were searched to determine relevant articles published in the English language. Our search deadline was May 2022. Critical Appraisal of Prognostic Studies was used to assess the quality for each article. Pooled hazard ratios (HRs) were used to evaluate the performance of LVSI in prognosis prediction. RESULTS: We enrolled 8 studies involving 25,352 patients published after 2010. Thus, high LVSI was an unfavorable factor in predicting overall survival (HR, 2.08; 95% confidence interval, 1.63-2.66; P = .006) and disease-free survival (HR, 2.20; 95% confidence interval, 1.79-2.70; P = .000) for patients with CC. However, the disease-free survival and overall survival were significantly different on univariate analysis based on the subgroup analysis stratified by analysis method, but no obvious heterogeneity was found across diverse articles. CONCLUSIONS: The present study showed that LVSI predicts the poor prognostic outcome of stage IA to IIB CC. However, well-designed clinical articles should further assess the independent prognosis prediction performance of LVSI in CC.

Novel Prognostic Biomarkers for Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) Patients via Analysis of Competing Endogenous RNA (ceRNA) Network.

Background: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is a common malignant gynecological cancer. The ceRNA networks play important roles in many tumors, while RILPL2-related ceRNA network has been seldom studied in CESC. Methods: All CESC data was obtained from TCGA database. Differentially expressed RNAs and predicted target RNAs were cross analyzed to construct ceRNA network. RNA and clinicopathological characteristics' influence on overall survival (OS) were determined by univariate and multivariate Cox regression analyses. Lasso regression was used to construct the prediction model. Coexpression analysis was performed to explore the association of gene expression with CESC. This was followed by an experimental validation based on these results. Results: Between high and low RILPL2 expression CESC patients, totally 1227 DEmRNAs, 39 DEmiRNAs, and 1544 DElncRNAs were identified. After multiple cross analyses, 1 miRNA hsa-miR-1293, 20 mRNAs, and 43 lncRNAs were maintained to construct ceRNA network. CADM3-AS1, LINC00092, and ZNF667-AS1 in ceRNA network were significantly associated with the OS of CESC patients, and patients with low expression of these lncRNAs had worse prognosis. Significant lower expressions of these lncRNAs were also observed in CESC cell line compared with normal cell line. Conclusion: Low expressions of CADM3-AS1, LINC00092, and ZNF667-AS1 in ceRNA network were probably promising poor prognostic biomarkers for CESC patients. The genes show a prospective research area for CESC-targeted treatment in the future.

Cod (Gadus) skin collagen peptide powder reduces inflammation, restores mucosal barrier function, and inhibits fibrosis in dextran sodium sulfate-induced colitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology. Cod (Gadus), a kind of herb from the Chinese herb. Traditionally, it has used to treat trauma, reduce swelling and relieve pain in order to exert its anti-inflammatory activity. Recent reports based on its hydrolyzed or enzymatic extracts have shown its anti-inflammatory, mucosal barrier protecting properties. However, its mechanism of improvement in ulcerative colitis is not clear. AIM OF THE STUDY: This study aimed to explore the preventive and protective effect of cod skin collagen peptide powder (CP) on mice with UC and to explore the underlying mechanism. MATERIALS AND METHODS: Mice with dextran sodium sulfate (DSS)-induced UC were treated with CP by gavage, and the anti-inflammatory effects of CP were assessed using general physical, pro-inflammatory cytokine, histopathological, immunohistochemical, macrophage flow cytometry, and inflammatory signaling pathway assays. RESULTS: CP ameliorates inflammation by upregulating mitogen-activated protein kinase phosphatase-1 (MKP-1) and thereby decreasing the phosphorylation levels of P38 and JNK. It also polarizes macrophages in the colon towards the M2 phenotype, which helps to reduce tissue damage and promotes colon repair. At the same time, CP also inhibits the development of fibrosis, one of the complications of UC, by upregulating ZO-1, Occludin, and downregulating α-SMA, Vimentin, Snail, and Slug. CONCLUSION: In this study, we found CP reduced inflammation in mice with UC by inducing MKP-1 expression, which caused dephosphorylation of mitogen-activated protein kinase (MAPK). CP also restored mucosal barrier function and inhibited the development of fibrosis complicating UC in these mice. Taken together, these results suggested that CP improved the pathological manifestations of UC in mice, suggesting that it can play a biological role as a nutritional supplement for preventing and treating UC.

Prognostic value of lymph node ratio in cervical cancer: A meta-analysis.

BACKGROUND: The role of the lymph node ratio (LNR) in the existing tumor node metastasis classification system should be verified as one of the prognosis prediction factors. This work evaluated LNR's performance in predicting cervical cancer (CC) prognosis through a meta-analysis. METHOD: Related studies were retrieved from the Cochrane Library, EMBASE, and PubMed databases. The language was restricted to English. The combined hazard ratios (HRs) were utilized to analyze the prognostic value of LNR. RESULTS: Our study included 8 articles with 3325 subjects published after 2015. Based on our analysis, high LNR was the adverse prognostic factor for overall survival (OS, HR = 1.45; 95% CI = 1.23-1.73; P = .238) and disease-free survival (DFS, HR = 2.69; 95% CI = 1.98-3.66; P = .597) among the CC cases. Furthermore, as revealed by subgroup analysis, in CC patients, median LNR of about 0.0625 and 0.066 served as the prominent risk factor for DFS and OS. CONCLUSIONS: The current work illustrates that elevated LNR is related to the dismal prognosis of CC. More well-designed clinical studies are warranted for assessing whether LNR is a factor independently predicting the prognosis of CC.

Effects of cGMP/Akt/GSK-3ß signaling pathway on atrial natriuretic peptide secretion in rabbits with rapid atrial pacing.

Atrial natriuretic peptide (ANP) plays a pivotal role in the regulation of the cardiovascular system. The ANP level increases during atrial fibrillation (AF), suggesting that AF may provoke ANP secretion, but its potential mechanism is still unclear. In the present study, the potential mechanisms of rapid atrial pacing (RAP) regulating ANP secretion was explored. Rabbits were subjected to burst RAP, ANP secretion increased whereas cyclic guanosine monophosphate (cGMP) concentrations decreased during RAP. The p-Akt and p-GSK-3ß levels decreased in atrial tissues. Natriuretic peptide receptor A (NPR-A) protein and particulate guanylate cyclase (PGC) activity were detected. The sensitivity of NPR-A to ANP decreased, leading to the decrease of PGC activity. Also, the isolated atrial perfusion system were made in the rabbit model, cGMP was shown to inhibit ANP secretion, and the Akt inhibitor LY294002 (LY) and GSK-3ß inhibitor SB216763 (SB) attenuated the inhibitory effects of cGMP on ANP secretion and enhanced the inhibitory effects of cGMP on atrial dynamics. In conclusion, NPR-A interacts with ANP to regulate PGC expression, and influence the expression of cGMP during RAP, which involves in the Akt/GSK-3ß signaling pathway. From the aforementioned points we conclude that cGMP regulates ANP secretion by the Akt/GSK-3ß signaling pathway during atrial pacing.

Smart Peptide Defense Web In Situ Connects for Continuous Interception of IgE against Allergic Rhinitis.

Allergic rhinitis (AR) is a chronic inflammatory reaction by immunoglobulin E (IgE) mediators after individual contact with allergens. It affects 10-40% of the world's population and reduces the quality of life. Long-term symptoms of rhinitis can cause inflammation to spread and trigger asthma, which can harm human health. Herein, we develop a Smart PeptIde defeNse (SPIN) web technique, which in situ constructs a peptide web, trapping IgE against AR. Two candidate SPINs, SPIN-1 and SPIN-2, are designed with different IgE-binding sequences. The SPIN-1 or SPIN-2 is able to bind to IgE and transform from nanoparticles into entangled nanofibers. In turn, the web of SPIN-1 or SPIN-2 acts as a long-term trap of IgE to prevent the IgE from binding to mast cells. SPIN-1 or SPIN-2 (10 mg/kg) is able to treat AR model Balb/c mice with high efficiency and reduced symptoms of rhinitis and inflammatory factors, even better than a first-line clinical drug, cetirizine (10 mg/kg). For example, the amount of IL-4 released in the AR group (185.5 ± 6.8 pg/mL) is significantly reduced after the treatment with SPIN-1 (70.4 ± 14.1 pg/mL), SPIN-2 (86.0 ± 9.3 pg/mL), or cetirizine (112.8 ± 19.3 pg/mL). More importantly, compared with the cetirizine group (1 day), the SPIN-1 or SPIN-2 group shows long-term therapeutic effects (1 week). The SPIN web technique shows the great potential for blocking IgE binding to mast cells in vivo, attenuating AR or other allergic reactions.

Preparation of photocrosslinkable polystyrene methylene cinnamate nanofibers via electrospinning.

Nanoscaled photocrosslinkable polystyrene methylene cinnamate (PSMC) nanofibers were fabricated by electrospinning. The PSMC was prepared by the modification of polystyrene as a starting material via a two-step reaction process, chloromethylation and esterification. The chemical structure of PSMC was confirmed by 1H NMR and Fourier transform infrared spectroscopy (FT-IR). The photosensitivity of the PSMC was investigated using ultraviolet (UV) spectroscopic methods. Electrospun PSMC nanofiber mat showed excellent solubility in many organic solvents. UV irradiation of the electrospun mats led to photodimerization to resist dissolving in organic solvents. The morphology of the nanofiber was observed by scanning electron microscopy (SEM) and the result indicated that the average diameter of nanofibers is 350 nm and the crosslinked nanofibers were not collapsed after dipping into organic solvent showing good solvent-stability. This photocrosslinked nanofibers has the potential application in filtration, catalyst carrier and protective coating.

Prognostic Value of MTV and TLG of 18F-FDG PET in Patients with Stage I and II Non-Small-Cell Lung Cancer: a Meta-Analysis.

Purpose: The present systematic literature review and meta-analysis focused on examining the significance of total lesion glycolysis (TLG) and metabolic tumor volume (MTV) in predicting the prognosis of stages I/II non-small-cell lung cancer (NSCLC) based on 18F-FDG PET parameters. Methods: Electronic databases, including Cochrane Library, PubMed, and EMBASE, were comprehensively searched for retrieving relevant articles published in the English language. Furthermore, the significance of TLG and MTV in prognosis prediction was analyzed by pooled hazard ratios (HRs). Results: This work enrolled eight primary studies with 1292 I/II-stage NSCLC cases. The pooled HR (95% confidence interval [CI]) for the ability of increased TLG to predict progression-free survival (PFS) was 2.02 (1.30-2.13) (P=0.350), while for increased MTV it was 3.04 (1.92-4.81) (P=0.793). In addition, the pooled HR (95% CI) for the ability of increased TLG to predict overall survival (OS) was 2.16 (1.49-3.14) (P=0.624). However, higher MTV correlated with OS, and sensitivity analysis showed that the results were not stable. Multivariate and univariate analyses by subgroup analyses stratified by PFS of MTV and OS of TLG exhibited statistically significant differences, without any statistical heterogeneity across various articles. Conclusion: The present work suggests the predictive value of PET/CT among stage I and II NSCLC patients. Our results verified that stage I/II NSCLC cases with increased TLG and MTV had a higher risk of side reactions, and TLG is related to increased mortality risk.

The Relationship of the TLR9 and TLR2 Genetic Polymorphisms with Cervical Cancer Risk: a Meta-Analysis of Case-Control Studies.

This meta-analysis aimed to assess the association of common TLR9 and TLR2 gene polymorphisms (TLR9 1486 T/C, TLR9 G2848A, and TLR2-196 to -174 del/ins) with cervical cancer risk. Studies were searched in Scopus, Pubmed, Embase, and CNKI until December 2017. Both fixed-effects and random-effects models were applied to combine odds ratio (OR) and 95% confidence intervals (95% CI). A total of 11 studies including 7856 participants were identified. The pooled estimation revealed an increased risk of cervical cancer in Caucasian subjects carrying the C allele of the TLR9 1486 T/C polymorphism (OR = 1.46, 95% CI: 1.11-1.92, p = 0.007), while there was a decreased risk in Mixed subjects carrying the C allele (OR = 0.35, 95% CI: 0.15-0.82, p = 0.016). Concerning the TLR9 G2848A polymorphism, the A allele was associated with an increased risk of cervical cancer in Caucasians (OR = 1.19, 95% CI: 1.02-1.40, p = 0.030), whereas Asian and Mixed subjects showed no significant associations. No significant associations were demonstrated between the TLR2-196 to -174 del/ins polymorphism and cervical cancer. Our findings suggest that the TLR9 1486 T/C and G2848A polymorphisms contribute to cervical cancer risk, but there is no association of the TLR2-196 to -174 del/ins polymorphism with cervical cancer.

A biomimetic peptide recognizes and traps bacteria in vivo as human defensin-6.

Using broad-spectrum antibiotics for microbial infection may cause flora disequilibrium, drug-resistance, etc., seriously threatening human health. Here, we design a human defensin-6 mimic peptide (HDMP) that inhibits bacterial invasion in vivo through mimicking the mechanisms of human defensin-6 with high efficiency and precision. The HDMP with ligand and self-assembling peptide sequence recognizes bacteria through ligand-receptor interactions and subsequently traps bacteria by an in situ adaptive self-assembly process and resulting nanofibrous networks; these trapped bacteria are unable to invade host cells. In four animal infection models, the infection rate was markedly decreased. Notably, administration of HDMP (5 mg/kg) nanoparticles increased the survival rate of mice with methicillin-resistant S. aureus bacteremia by as much as 100%, even more than that of vancomycin treatment (5 mg/kg, 83.3%)-treated group, the golden standard of antibiotics. This biomimetic peptide shows great potential as a precise and highly efficient antimicrobial agent.

Prognostic value of maximum standard uptake value, metabolic tumor volume, and total lesion glycolysis of positron emission tomography/computed tomography in patients with breast cancer: A systematic review and meta-analysis.

PURPOSE: A comprehensive systematic review of the literature was conducted on parameters from 18 F-FDG PET and a meta-analysis of the prognostic value of the maximal standard uptake value (SUVmax), metabolic tumor volume (MTV) and total lesional glycolysis (TLG) in patients with breast cancer (BC). PATIENTS AND METHODS: Relevant English articles from PubMed, EMBASE, and the Cochrane Library were retrieved. Pooled hazard ratios (HRs) were used to assess the prognostic value of SUVmax, MTV, and TLG. RESULTS: A total of 20 primary studies with 3115 patients with BC were included. The combined HRs (95% confidence interval [CI] of higher SUVmax and higher TLG for event-free survival (EFS) were 1.53 (95% CI, 1.25-1.89, P = 0.0006) and 5.94 (95% CI, 2.57-13.71, P = 0.97), respectively. Regarding the overall survival (OS), the combined HRs were 1.22 (95%CI, 1.02-1.45, P = 0.0006) with higher SUVmax, and 2.91(95% CI, 1.75-4.85, P = 0.44) with higher MTV. Higher MTV showed no correlation with EFS [1.31(95% CI, 0.65-2.65, P = 0.18)] and similarly higher TLG showed no correlation with OS [1.20(95% CI, 0.65-2.23, P = 0.45)]. Subgroup analysis showed that SUVmax, with a median value of 5.55 was considered as a significant risk factor for both EFS and OS in BC patients. CONCLUSION: Despite clinically heterogeneous BC patients and adoption of various methods between studies, the present meta-analysis results confirmed that patients with high SUVmax are at high risk of adverse events or death in BC patients, high MTV predicted a high risk of death and high TLG predicted a high risk of adverse events.