Association of mean pericoronary adipose tissue attenuation with different demographic factors in a subgroup of patients without coronary artery disease stratified by sex, body mass index, and age.

Background: In patients without coronary artery disease (CAD), few studies have evaluated the association between mean pericoronary adipose tissue attenuation (PCATMA) and patient-based demographic factors, for example, age or sex. Therefore, the purpose of this study is to investigate the association between PCATMA and various demographic factors in patients without CAD. Methods: In this case-control study, the 806 patients who underwent coronary computed tomography angiography and were not diagnosed with CAD between July 2020 and July 2022 were retrospectively enrolled. Their PCATMA values of the proximal right coronary artery were measured automatically. Patients without CAD were stratified according to sex, body mass index (BMI), and age, and the relationship between PCATMA and different clinical characteristics was explored using Fisher's exact test or Chi-squared test and independent t-tests or Wilcoxon Mann-Whitney U tests. Results: Compared to non-smoking women [-88.00 (-95.00, -81.00) HU], women who smoked [-84.00 (-94.00, -78.00) HU, P=0.037] had higher PCATMA values and a positive correlation with PCATMA (rs=0.101, P=0.036). Compared to non-hypertensive patients with BMI ≥24.91 kg/m2 [-87.00 (-95.00, -81.00) HU], hypertensive patients with BMI ≥24.91 kg/m2 [-84.00 (-92.00, -78.00) HU, P=0.004] had higher PCATMA values, and a positive correlation with PCATMA (rs=0.144, P=0.004). In a subgroup of patients without CAD stratified by sex, BMI, and age, PCATMA values were all higher in patients with dyslipidemia (women, men, BMI ≥24.91 kg/m2, BMI <24.91 kg/m2, age ≥55 years, and age <55 years: -82.00, -82.00, -81.50, -82.00, -81.00 and -83.50 HU, respectively) than in those without dyslipidemia (-89.00, -89.00, -89.00, -90.00, -90.00 and -88.00 HU, respectively; all P<0.001) and showed a positive relationship (rs=0.328, 0.339, 0.342, 0.326, 0.367, and 0.298, respectively; all P<0.001). Conclusions: Higher PCATMA attenuation values were observed in patients with dyslipidemia, smoking women, and hypertensive patients with BMI ≥24.91 kg/m2, suggesting that PCATMA values can be used to detect patients at high risk for future events with CAD even if they do not currently have atherosclerosis.

Refining the 8th edition TNM classification for EBV related nasopharyngeal carcinoma.

The AJCC/UICC TNM classification describes anatomic extent of tumor progression and guides treatment decisions. Our comprehensive analysis of 8,834 newly diagnosed patients with non-metastatic Epstein-Barr virus related nasopharyngeal carcinoma (NPC) from six Chinese centers indicates certain limitations in the current staging system. The 8th edition of the AJCC/UICC TNM classification inadequately differentiates patient outcomes, particularly between T2 and T3 categories and within the N classification. We propose reclassifying cases of T3 NPC with early skull-base invasion as T2, and elevating N1-N2 cases with grade 3 image-identified extranodal extension (ENE) to N3. Additionally, we suggest combining T2N0 with T1N0 into a single stage IA. For de novo metastatic (M1) NPC, we propose subdivisions of M1a, defined by 1-3 metastatic lesions without liver involvement, and M1b, characterized by >3 metastatic lesions or liver involvement. This proposal better reflects responses of NPC patients to the up-to-date treatments and their evolving risk profiles.

Optimal Size Threshold for MRI-Detected Retropharyngeal Lymph Nodes to Predict Outcomes in Nasopharyngeal Carcinoma: A Two-Center Study.

BACKGROUND. Retropharyngeal lymph node (RLN) metastases have profound prognostic implications in patients with nasopharyngeal carcinoma (NPC). However, the AJCC staging system does not specify a size threshold for determining RLN involvement, resulting in inconsistent thresholds in practice. OBJECTIVE. The purpose of this article was to determine the optimal size threshold for determining the presence of metastatic RLNs on MRI in patients with NPC, in terms of outcome predictions. METHODS. This retrospective study included 1752 patients (median age, 46 years; 1297 men, 455 women) with NPC treated by intensity-modulated radiotherapy (RT) from January 2010 to March 2014 from two hospitals; 438 patients underwent MRI 3-4 months after treatment. Two radiologists measured the minimal axial diameter (MAD) of the largest RLN for each patient using a consensus process. A third radiologist measured MAD in 260 randomly selected patients to assess interobserver agreement. Initial ROC and restricted cubic spline (RCS) analyses were used to derive an optimal MAD threshold for predicting progression-free survival (PFS). The threshold's predictive utility was assessed in multivariable Cox regression analyses, controlling for standard clinical predictors. The threshold's utility for predicting PFS and overall survival (OS) was compared with a 5-mm threshold using Kaplan-Meier curves and log-rank tests. RESULTS. The intraclass correlation coefficient for MAD was 0.943. ROC and RCS analyses yielded an optimal threshold of 6 mm. In multivariable analyses, MAD of 6 mm and greater independently predicted PFS in all patients (HR = 1.35, p = .02), patients with N0 or N1 disease (HR = 1.80, p = .008), and patients who underwent posttreatment MRI (HR = 1.68, p = .04). In patients with N1 disease without cervical lymph node involvement, 5-year PFS was worse for MAD greater than or equal to 6 mm than for MAD that was greater than or equal to 5 mm but less than 6 mm (77.2% vs 89.7%, p = .03). OS was significantly different in patients with stage I and stage II disease defined using a 6-mm threshold (p = .04), but not using a 5-mm threshold (p = .09). The 5-year PFS rate was associated with a post-RT MAD of 6 mm and greater (HR = 1.68, p = .04) but not a post-RT MAD greater than or equal to 5 mm (HR = 1.09, p = .71). CONCLUSION. The findings support a threshold MAD of 6 mm for determining RLN involvement in patients with NPC. CLINICAL IMPACT. Future AJCC staging updates should consider incorporation of the 6-mm threshold for N-category and tumor-stage determinations.

Hypobaric Hypoxia Aggravates Renal Injury by Inducing the Formation of Neutrophil Extracellular Traps through the NF-κB Signaling Pathway.

OBJECTIVE: The hypersensitivity of the kidney makes it susceptible to hypoxia injury. The involvement of neutrophil extracellular traps (NETs) in renal injury resulting from hypobaric hypoxia (HH) has not been reported. In this study, we aimed to investigate the expression of NETs in renal injury induced by HH and the possible underlying mechanism. METHODS: A total of 24 SD male rats were divided into three groups (n=8 each): normal control group, hypoxia group and hypoxia+pyrrolidine dithiocarbamate (PDTC) group. Rats in hypoxia group and hypoxia+PDTC group were placed in animal chambers with HH which was caused by simulating the altitude at 7000 meters (oxygen partial pressure about 6.9 kPa) for 7 days. PDTC was administered at a dose of 100 mg/kg intraperitoneally once daily for 7 days. Pathological changes of the rat renal tissues were observed under a light microscope; the levels of serum creatinine (SCr), blood urea nitrogen (BUN), cell-free DNA (cf-DNA) and reactive oxygen species (ROS) were measured; the expression levels of myeloperoxidase (MPO), citrullinated histone H3 (cit-H3), B-cell lymphoma 2 (Bcl-2), Bax, nuclear factor kappa B (NF-κB) p65 and phospho-NF-κB p65 (p-NF-κB p65) in rat renal tissues were detected by qRT-qPCR and Western blotting; the localization of NF-κB p65 expression in rat renal tissues was observed by immunofluorescence staining and the expression changes of NETs in rat renal tissues were detected by multiplex fluorescence immunohistochemical staining. RESULTS: After hypoxia, the expression of NF-κB protein in renal tissues was significantly increased, the levels of SCr, BUN, cf-DNA and ROS in serum were significantly increased, the formation of NETs in renal tissues was significantly increased, and a large number of tubular dilatation and lymphocyte infiltration were observed in renal tissues. When PDTC was used to inhibit NF-κB activation, NETs formation in renal tissue was significantly decreased, the expression level of Bcl-2 in renal tissues was significantly increased, the expression level of Bax was significantly decreased, and renal injury was significantly alleviated. CONCLUSION: HH induces the formation of NETs through the NF-κB signaling pathway, and it promotes apoptosis and aggravates renal injury by decreasing Bcl-2 and increasing Bax expression.

Tislelizumab plus chemotherapy as first-line treatment for recurrent or metastatic nasopharyngeal cancer: A multicenter phase 3 trial (RATIONALE-309).

Checkpoint inhibitors are effective in recurrent/metastatic nasopharyngeal cancer (R/M NPC). RATIONALE-309 (NCT03924986) randomized 263 treatment-naive R/M NPC patients to tislelizumab or placebo every 3 weeks (Q3W), plus chemotherapy (Q3W for 4-6 cycles). At interim analysis, progression-free survival (PFS) was significantly longer with tislelizumab-chemotherapy versus placebo-chemotherapy (hazard ratio: 0.52; 95% confidence interval: 0.38, 0.73; p < 0.0001). PFS benefit for tislelizumab-chemotherapy versus placebo-chemotherapy was observed regardless of programmed death-ligand 1 expression. PFS after next line of treatment and overall survival showed favorable trends for tislelizumab-chemotherapy versus placebo-chemotherapy. The safety profile was similar between arms. Gene expression profiling (GEP) identified immunologically "hot" tumors, and showed an activated dendritic cell (DC) signature was associated with tislelizumab-chemotherapy PFS benefit. Our results support that tislelizumab-chemotherapy should be considered as first-line treatment for R/M NPC, and GEP and activated DC signature results may help identify patients who might benefit most from immunochemotherapy treatment. VIDEO ABSTRACT.

Integrating Tetrathiafulvalene and Nickel-Bis(dithiolene) Units into Donor-Acceptor Covalent Organic Frameworks for Stable and Efficient Photothermal Conversion.

Tetrathiafulvalene (TTF) and Ni-bis(dithiolene) are typical conductive units widely studied in electronics, optics, and photochemistry. However, their applications in near-infrared (NIR) photothermal conversion are often limited by insufficient NIR absorption and low chemical/thermal stability. Herein, we integrate TTF and Ni-bis(dithiolene) into a covalent organic framework (COF) with stable and efficient NIR and solar photothermal conversion performance. Two isostructural COFs, namely Ni-TTF and TTF-TTF, are successfully isolated which are composed of TTF and Ni-bis(dithiolene) units as donor-acceptor (D-A) pairs or TTF units only. Both COFs show high BET surface areas and good chemical/thermal stability. Notably, compared with TTF-TTF, the periodic D-A arrangement in Ni-TTF significantly lowers the bandgap, leading to unprecedented NIR and solar photothermal conversion performance.

Spinal Fusion Versus Repeat Discectomy for Recurrent Lumbar Disc Herniation: A Systematic Review and Meta-Analysis.

OBJECTIVE: Recurrent lumbar disc herniation (RLDH) is one of the major causes of failure for primary surgery. Repeat discectomy (RD) and spinal fusion (SF) are 2 surgical options for RLDH. The objective of our study is to compare the effectiveness of SF compared with RD in the treatment of RLDH. METHODS: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and Ovid Medline for studies (published between Jan 1, 1959 and July 8, 2022; no language restriction) comparing SF and RD for the RLDH. Odds ratio and weighted mean difference were calculated for binary outcomes and continuous outcomes. The quality of each outcome was graded using the Grading of Recommendations, Assessment, Development and Evaluations criteria. RESULTS: We identified 5029 studies, of which 11 studies were included. There were 2 randomized controlled trials and the remaining were observational studies. Comparing SF and RD groups, no differences were found in visual analog scales for leg and back and Oswestry Disability Index. Furthermore, the Japanese Orthopaedic Association scores of SF were significantly higher than the RD group. In terms of complications, the incidence of neurological deficit, segmental instability, and re-recurrence is significantly lower with SF than with the RD group. Lastly, the SF group was associated with longer hospital stays and operation time, and more blood loss. CONCLUSIONS: The pooled evidence suggests that fusion achieves better results than RD for RLDH. The results of this review should be further confirmed by future high-quality randomized controlled trials.

Yanghe decoction attenuated pain hypersensitivity induced by michigan cancer foundation-7 injection in rats with bone metastases from breast cancer by inhibiting transient receptor potential ankyrin 1.

OBJECTIVE: To study the effect and underlying mechanisms of Chinese medicine Yanghe decoction on pain relief in a rat model of bone metastasis of breast cancer induced by michigan cancer foundation-7 (MCF-7). METHODS: Bone pain was induced in the tibia of rats injected with MCF-7 cells. The Chinese herbal remedy was used to decoct Yanghe decoction for the treatment of bone pain rats. The behavior study was carried out to evaluate the paw mechanical withdraw threshold and thermal withdraw latency. Liquid chromatography-mass spectrometry, Western blotting, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA), immunohistochemical (IHC) staining were performed for analysis. RESULTS: Yanghe decoction could improve the defensive behavior similar to the transient receptor potential ankyrin 1 (TRPA1) inhibitor. In morphology study, Yanghe decoction could attenuate the cellular growth as well as inflammatory infiltration in the metastasis group. Furthermore, Yanghe decoction downregulated the TRPA1 expression on the dorsal root ganglion from the metastatic rats at both transcriptional and protein level. Yanghe decoction alleviated the inflammation in metastatic tissues by hematoxylin-eosin and IHC analysis, and Yanghe decoction also reduced the inflammatory cytokines production in the serum including tumor necrosis factor-α and interleukin-6, interleukin-1 beta by ELISA. As the cytochromec oxidase subunit II/prostaglandin E2 (PGE2) is required for cancer development, Yanghe decoction reduced the expression of PGE2 in the tissue and serum. CONCLUSION: Taken together, Yanghe decoction protected the rats from breast cancer bone metastasis through TRPA1 signaling mediated neuropathic pain and additional immune modulation in tumor microenvironment.

Rosiglitazone attenuates hypoxia-induced renal cell apoptosis by inhibiting NF-κB signaling pathway in a PPARγ-dependent manner.

BACKGROUND: In recent years, peroxisome proliferator-activated receptor γ (PPARγ) has been found to be closely associated with hypoxia renal disease. The aim of this study was to investigate the relationship between rosiglitazone and mitochondrial apoptosis in renal tissue and its associated mechanisms. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into three groups (n = 8 in each): normal control group, hypoxia injury group (equal volume of 0.9% saline), and PPARγ agonist group (Rosiglitazone, 10 mg/kg · d, intraperitoneally). The hypoxia injury group and PPARγ agonist group were placed in a hypoxia chamber and the simulated altitude was set at 7,000 m for 7 days. Blood and kidney samples were collected after 7 days. The quantitative real-time polymerase chain reaction and Western blot methods were used to determine the expression of PPARγ, nuclear factor kappa-B (NF-κB), B-cell lymphoma-2 (Bcl-2), and Bax. RESULTS: The results showed that compared with the normal control group, the renal tissue of rats after hypoxia was severely damaged, as shown by massive renal tubular epithelial cell degeneration and detachment, and renal tubular dilation. The NF-κB protein expression significantly increased, the Bcl-2 protein and mRNA expression significantly decreased, and Bax protein and mRNA expression significantly increased (p < .05 for all). Renal injury was much less severe in the PPARγ agonist group compared to the hypoxia injury group. CONCLUSIONS: Rosiglitazone can alleviate hypoxia renal injury, with the possible mechanism involving attenuation of apoptosis by inhibiting the activation of the NF-κB signaling pathway in a PPARγ-dependent manner and increasing Bcl-2 and decreasing Bax expression.

Ameliorative Effects of Malonyl Ginsenoside from Panax ginseng on Glucose-Lipid Metabolism and Insulin Resistance via IRS1/PI3K/Akt and AMPK Signaling Pathways in Type 2 Diabetic Mice.

Our previous study has revealed that malonyl-ginsenosides from Panax ginseng (PG-MGR) play a crucial role in the treatment of T2DM. However, its potential mechanism was still unclear. In this study, we investigated the anti-diabetic mechanisms of action of PG-MGR in high fat diet-fed (HFD) and streptozotocin-induced diabetic mice and determined the main constituents of PG-MGR responsible for its anti-diabetic effects. Our results showed that 16 malonyl ginsenosides were identified in PG-MGR by HPLC-ESI-MS/MS. PG-MGR treatment significantly reduced fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels and improved insulin resistance and glucose tolerance. Simultaneously, PG-MGR treatment improved liver injury by decreasing aspartate aminotransferase (AST) and alanine aminotransferase (ALT) expression. Furthermore, Western blot analysis demonstrated that the protein expression levels of p-PI3K/PI3K, p-AKT/AKT, p-AMPK/AMPK, p-ACC/ACC and GLUT4 in liver and skeletal muscle were significantly up-regulated after PG-MGR treatment, and the protein expression levels of p-IRS-1/IRS-1, Fas and SREBP-1c were significantly reduced. These findings revealed that PG-MGR has the potential to improve glucose and lipid metabolism and insulin resistance by activating the IRS-1/PI3K/AKT and AMPK signal pathways.

Comprehensive Analysis of Secondary Metabolites in the Extracts from Different Lily Bulbs and Their Antioxidant Ability.

The genus Lilium contains more than 100 wild species and numerous hybrid varieties. Some species of them have been used as medicine and food since ancient times. However, the research on the active components and the medical properties of lilies has only focused on a few species. In this study, the total phenolic acid content (TPC), total flavonoid content (TFC), and antioxidant capacity of 22 representative lilies were systematically investigated. The results showed that the TPC, TFC and antioxidant activity were highly variable among different lilies, but they were significantly positively correlated. Hierarchical cluster analysis indicated that L. henryi and L. regale were arranged in one group characterized by the highest TPC, TFC and antioxidant capacity, followed by Oriental hybrids and Trumpet and Oriental hybrids. The traditional edible and medicinal lilies were clustered in low TPC, TFC and antioxidant capacity group. A total of 577 secondary metabolites, including 201 flavonoids, 153 phenolic acids, were identified in the five species with great differences in antioxidant capacity by extensive targeted metabonomics. Differentially accumulated metabolites (DAMs) analysis reviewed that the DAMs were mainly enriched in secondary metabolic pathways such as isoflavonoid, folate, flavonoid, flavone, flavonol, phenylpropanoid, isoquinoline alkaloid biosynthesis, nicotinate and nicotinamide metabolism and so on. Correlation analysis identified that 64 metabolites were significantly positively correlated with antioxidant capacity (r ≥ 0.9 and p < 0.0001). These results suggested that the genus Lilium has great biodiversity in bioactive components. The data obtained greatly expand our knowledge of the bioactive constituents of Lilium spp. Additionally, it also highlights the potential application of Lilium plants as antioxidants, functional ingredients, cosmetic products and nutraceuticals.

Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: The addition of camrelizumab to gemcitabine and cisplatin showed promising activity as first-line therapy in patients with recurrent or metastatic nasopharyngeal carcinoma in a phase 1 trial. We therefore compared camrelizumab plus gemcitabine and cisplatin with placebo plus gemcitabine and cisplatin in a randomised phase 3 trial. METHODS: In this randomised, double-blind, phase 3 trial done at 28 hospitals in China, patients were eligible if they were aged 18-75 years, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and had previously untreated recurrent or metastatic nasopharyngeal carcinoma. Patients were randomly assigned (1:1; using an interactive web-response system with a block size of four) to receive either camrelizumab (200 mg on day 1) or matching placebo intravenously, plus gemcitabine and cisplatin (gemcitabine 1000 mg/m2 on days 1 and 8; cisplatin 80 mg/m2 on day 1) intravenously every 3 weeks for four to six cycles, followed by maintenance therapy with camrelizumab or placebo, until radiographic progression, unacceptable toxicity, start of new anticancer treatment, investigator decision, or withdrawal of consent. Stratification factors used in randomisation were liver metastases, previous radical concurrent chemoradiotherapy, and ECOG performance status. The allocation sequence was generated by an independent randomisation group. The primary endpoint was progression-free survival per independent review committee. The significance threshold for independent review committee-assessed progression-free survival was p=0·0086 (one-sided) at the interim analysis. Efficacy and safety analyses included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03707509, and is closed for enrolment but is ongoing. FINDINGS: Between Nov 13, 2018, and Nov 29, 2019, 343 patients were screened and 263 were eligible and were randomly assigned to the camrelizumab group (n=134) or placebo group (n=129). At the prespecified interim analysis (June 15, 2020), independent review committee-assessed progression-free survival was significantly longer in the camrelizumab group (median 9·7 months [95% CI 8·3-11·4]) than in the placebo group (median 6·9 months [5·9-7·3]; hazard ratio 0·54 [95% CI 0·39-0·76]; one-sided p=0·0002). As of Dec 31, 2020, the most common grade 3 or worse adverse events of any cause were decreased white blood cell count (89 [66%] of 134 patients in the camrelizumab group vs 90 [70%] of 129 patients in the placebo group), decreased neutrophil count (86 [64%] vs 85 [66%]), anaemia (53 [40%] vs 57 [44%]), and decreased platelet count (53 [40%] vs 52 [40%]). Serious adverse events were reported in 59 (44%) of 134 patients in the camrelizumab group and 48 (37%) of 129 patients in the placebo group. Treatment-related deaths occurred in five (4%) patients in the camrelizumab group (two unknown cause of death, one multiple organ dysfunction syndrome, one pharyngeal haemorrhage, and one arrhythmia) and one (<1%) patient in the placebo group (unknown cause of death). INTERPRETATION: Our findings suggest that camrelizumab plus gemcitabine and cisplatin could be a new standard of care for patients with recurrent or metastatic nasopharyngeal carcinoma in the first-line setting. Longer follow-up is needed to confirm this conclusion. FUNDING: Jiangsu Hengrui Pharmaceuticals (formerly Jiangsu Hengrui Medicine). TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

The expression profiles and prognostic values of HSP70s in hepatocellular carcinoma.

BACKGROUND: The HSP70 family of heat shock protein plays a critical role in protein synthesis and transport to maintain protein homeostasis. Several studies have indicated that HSP70s are related to the development and occurrence of various cancers. METHODS: The relationship between the overall survival rate of hepatocellular carcinoma patients and the expression of 14 HSP70s from multiple databases, such as TCGA, ONCOMINE, cBioPortal was investigated. Western Blot and PCR were used to evaluate HSPA4 and HSPA14 expressions in various HCC cells to identify suitable cell lines for further experiments .Wound-healing assays, Transwell assays and EdU assays were used to verify the effects of HSPA4 and HSPA14 on the function of hepatocellular carcinoma cells, and statistical analysis was performed. RESULTS: Hepatocellular carcinoma tissues significantly expressed the 14 HSP70s compared to the normal samples. Besides, the high HSPA1A, HSPA1B, HSPA4, HSPA5, HSPA8, HSPA13, and HSPA14 expressions were inversely associated with the overall survival rate of patients, tumor grade, and cancer stage. A PPI regulatory network was constructed using the 14 HSP70s proteins with HSPA5 and HSPA8 at the network center. Univariate and multivariate analyses showed that HSPA4 and HSPA14 could be independent risk factors for the prognosis of hepatocellular carcinoma patients. Cell experiments have also confirmed that reducing HSPA4 and HSPA14 expressions can inhibit the invasion, metastasis, and proliferation of hepatocellular carcinoma cells. CONCLUSIONS: Therefore, the HSP70s significantly influence the occurrence and development of hepatocellular carcinoma. For instance, HSPA4 and HSPA14 can be novel therapeutic targets and prognostic biomarkers for hepatocellular carcinoma.

Application Value of Detection of High-Risk HPV Infection in Early Cervical Cancer Patients in Disease Diagnosis and Prognosis Evaluation.

BACKGROUND: To analyze the relationship between HPV infection and early cervical cancer and postoperative survival outcomes. METHODS: A total of 556 women were recruited to receive TCT and HPV tests from October 2017 to October 2018. The type of disease was pathologically diagnosed. The HPV positive rate, HPV-DNA, and E6/E7 mRNA quantitative level were detected, and the diagnostic accuracy of the subjects was analyzed by the receiver operating characteristic (ROC). The cervical intraepithelial neoplasia (CIN) and early cervical cancer patients were radically cured and followed up for 12.0 months to analyze the recurrence rate. RESULTS: Seventy-two cases of chronic cervicitis, 54 cases of CIN, and 51 cases of cervical cancer patients were pathologically diagnosed (32 cases in early stage and 19 cases in middle and late stage). HPV positive rate increased gradually in chronic cervicitis, CIN, and cervical cancer group (p < 0.001) and HPV 16 + 18 subtype. The positive rate was significantly different (p = 0.009). HPV-DNA and E6/E7 mRNA quantification also showed significant differences (p < 0.001). ROC analysis indicated that the accuracy of HPV-DNA and E6/E7 mRNA quantitative diagnosis of malignant lesions (CIN+ cervical cancer) were 0.865 and 0.879, respectively. There were 4 cases (7.41%) of recurrence in CIN group and 5 cases (15.63%) in early cervical cancer group. There was no difference (p = 0.401) among all of the patients. All patients with recurrence were HPV positive. CONCLUSIONS: HPV detection is an indispensable screening method for early cervical cancer and precancerous lesions, and comprehensive HPV 16 and 18 subtypes. DNA and E6/E7 mRNA quantification assay would further improve the accuracy of screening.

Long-Term Survival After Nasopharyngeal Carcinoma Treatment in a Local Prefecture-Level Hospital in Southern China.

PURPOSE: NPC is a malignant and invasive tumor with the incidence rate of 19/100,000 per year in Zhongshan City, a prefecture city in southern China. Long-term survival analysis on intensity-modulated radiotherapy (IMRT)-based treatment in local prefecture-level hospitals have not been investigated. We aimed to evaluate the 5-year clinical outcomes and prognostic factors of NPC treated with IMRT in Zhongshan City People's Hospital (ZSPH), a prefecture-level hospital in South China. PATIENTS AND METHODS: The number of 149 newly diagnosed non-metastatic NPC cases treated with IMRT were included from Zhongshan City People's Hospital between January 2010 and December 2011. The survival outcomes, treatment toxicities and prognostic factors were analyzed by Kaplan-Meier method and Cox proportional hazards model. RESULTS: With a median follow-up period of 65 months for the cohort, the 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS) and distant metastasis-free survival (DMFS) and overall survival (OS) were 86.80%, 94.80%, 86.10% and 80.50%, respectively. The 5-year OS rates were 100%, 95.2%, 87% and 67.2% for stage I, II, II and IVa-b, respectively (P=0.004). The 5-year LRFS rates were 97.2%, 96.0%, 90.4% and 72.0% for T1, T2, T3 and T4, respectively (P=0.001); the 5-year DMFS rates were 100% for T1, 96.8% for T2, 81.9% for T3 and 74.6% for T4 (P=0.022). A multivariate analysis revealed tumor stage as an independent prognostic factor for LRFS, DMFS and OS. No patients died from acute toxicities. Late toxicities were observed for 130 (87.2%) patients, and most late toxicities were graded I/II. CONCLUSION: NPC treatment effect in a prefecture-level hospital in South China was comparable to international results and toxicities were tolerable. Tumour stage was an independent prognostic factor for survival outcome. More NPC survival data from local and remote places are needed.

LncRNA GUSBP5-AS promotes EPC migration and angiogenesis and deep vein thrombosis resolution by regulating FGF2 and MMP2/9 through the miR-223-3p/FOXO1/Akt pathway.

Long non-coding RNAs (lncRNAs) play an essential role in multitudinous physiological and pathological processes, including vascular disease. We previously showed that lncRNA GUSBP5-AS (enst00000511042) is upregulated in endothelial progenitor cells (EPCs) of deep veni thrombosis (DVT) patients. Here, we investigate the role and mechanism of GUSBP5-AS in EPCs and DVT. Using the DVT model, we found that GUSBP5-AS significantly reduced the thrombus size and weight and enhanced the homing ability of EPC to DVT sites to promote resolution and recanalization of thrombus. GUSBP5-AS promoted cell cycle progression, proliferation, migration and invasion in EPCs, enhanced EPC angiogenesis in vitro and in vivo, and inhibited apoptosis. Strikingly, this study showed that GUSBP5-AS was unbalanced and modulated Forkhead Box Protein O1 (FOXO1) in EPCs in patients with DVT by interacting with miR-223-3p. Mechanistically, GUSBP5-AS functions as a sponge of miR-223-3p, which targets FOXO1. Both GUSBP5-AS knockdown and miR-223-3p overexpression remarkably inhibited angiogenesis, migration and invasion in EPCs. Additionally, our data suggested that GUSBP-AS activated the Akt pathway and enhanced fibroblast growth factor 2 (FGF2), matrix metalloproteinase-2/9 (MMP2/9) and F-actin expression. Taken together, this study indicates that GUSBP5-AS modulates angiogenesis, proliferation and homing ability of EPCs via regulating FGF2 and MMP2/9 expression through the miR-223-3p/FOXO1/Akt pathway, which may provide a new direction for the development of DVT therapeutics.

The regulatory role of microRNAs in angiogenesis-related diseases.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at a post-transcriptional level via either the degradation or translational repression of a target mRNA. They play an irreplaceable role in angiogenesis by regulating the proliferation, differentiation, apoptosis, migration and tube formation of angiogenesis-related cells, which are indispensable for multitudinous physiological and pathological processes, especially for the occurrence and development of vascular diseases. Imbalance between the regulation of miRNAs and angiogenesis may cause many diseases such as cancer, cardiovascular disease, aneurysm, Kawasaki disease, aortic dissection, phlebothrombosis and diabetic microvascular complication. Therefore, it is important to explore the essential role of miRNAs in angiogenesis, which might help to uncover new and effective therapeutic strategies for vascular diseases. This review focuses on the interactions between miRNAs and angiogenesis, and miRNA-based biomarkers in the diagnosis, treatment and prognosis of angiogenesis-related diseases, providing an update on the understanding of the clinical value of miRNAs in targeting angiogenesis.

Effects of periarticular injection on analgesic effects and NSAID use in total knee arthroplasty and total hip arthroplasty

OBJECTIVES: This study examined periarticular multimodal drug injection and the use of nonsteroidal anti-inflammatory drugs for an early analgesic effect after total knee arthroplasty and total hip arthroplasty. Patient satisfaction and benefits from the treatment were also assessed. METHODS: A total of 110 patients who were scheduled to undergo total knee arthroplasty and 86 patients who were scheduled to undergo total hip arthroplasty were divided into two groups, the study group and the control group. The study group received a periarticular multimodal drug injection during surgery. The control group received an equal volume of normal saline. All patients received an analgesia pump and a moderate dose of nonsteroidal anti-inflammatory drugs. Resting and motion Numeric Rating Scale scores, the Western Ontario and McMaster Universities Arthritis Index, knee or hip joint range of motion, length of postoperative hospital stay, patient satisfaction, total nonsteroidal anti-inflammatory drug consumption and side effects were recorded. RESULTS: Both study groups exhibited significant improvement in pain Numeric Rating Scale scores during rest and exercise several days after the surgery. The range of joint motion was greater in the study group, and the length of postoperative hospital stay was shorter than that in the control group. Patients in the study group consumed fewer nonsteroidal anti-inflammatory drugs and reported greater satisfaction with surgery. CONCLUSION: Intraoperative periarticular multimodal drug injection significantly relieved pain after surgery and reduced nonsteroidal anti-inflammatory drug consumption. These patient had a better postoperative experience, including satisfaction and rehabilitation.

[Remediation of Decabromodiphenyl Ether Contaminated Sediment Through Plant Roots Enhanced by Exogenous Microbes].

Decabromodiphenyl ether (BDE-209), a main ingredient of brominated flame retardants, has drawn more and more attention because of the pollution it caused in sediment. A pot experiment was conducted in a greenhouse to investigate the impact of Brevibacillus brevis and Enterococcus casselifavus on the enhancement of phytoremediation by Thalia dealbata, which is common in the river bank and was found to be an effective plant for BDE-209 removal. The concentration of organic acids, the amount of microorganisms and the ability of carbon utilization of soil microorganisms in different experimental groups were analyzed. The results showed that the removal rate of BDE-209 in the exogenous microbes containing groups were higher than that of the control. And B. brevis presented the highest enhancement of phytoremediation with the removal rate rising highest to 66% compared with the control (non-rhizosphere group 37.93% and no plant group 39.27%) after 60 days. The removal of BDE-209 in sediment, quantity of microorganism, concentration of organic acids and the ability of carbon utilization of soil microorganisms in rhizosphere sediment were higher than those in non-rhizosphere sediment.

Effects of periarticular injection on analgesic effects and NSAID use in total knee arthroplasty and total hip arthroplasty.

OBJECTIVES: This study examined periarticular multimodal drug injection and the use of nonsteroidal anti-inflammatory drugs for an early analgesic effect after total knee arthroplasty and total hip arthroplasty. Patient satisfaction and benefits from the treatment were also assessed. METHODS: A total of 110 patients who were scheduled to undergo total knee arthroplasty and 86 patients who were scheduled to undergo total hip arthroplasty were divided into two groups, the study group and the control group. The study group received a periarticular multimodal drug injection during surgery. The control group received an equal volume of normal saline. All patients received an analgesia pump and a moderate dose of nonsteroidal anti-inflammatory drugs. Resting and motion Numeric Rating Scale scores, the Western Ontario and McMaster Universities Arthritis Index, knee or hip joint range of motion, length of postoperative hospital stay, patient satisfaction, total nonsteroidal anti-inflammatory drug consumption and side effects were recorded. RESULTS: Both study groups exhibited significant improvement in pain Numeric Rating Scale scores during rest and exercise several days after the surgery. The range of joint motion was greater in the study group, and the length of postoperative hospital stay was shorter than that in the control group. Patients in the study group consumed fewer nonsteroidal anti-inflammatory drugs and reported greater satisfaction with surgery. CONCLUSION: Intraoperative periarticular multimodal drug injection significantly relieved pain after surgery and reduced nonsteroidal anti-inflammatory drug consumption. These patient had a better postoperative experience, including satisfaction and rehabilitation.