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BackgroundFew studies have focused specifically on prognostic factors and optimal surgical intervention for early-onset triple-negative breast cancer (eTNBC), which is characterized by high malignancy and poor prognosis.MethodsWe performed a cohort study with a median follow-up of 31 months using Surveillance, Epidemiology, and End Results (SEER) data of patients diagnosed with stages I–III eTNBC between 2010 and 2016. In addition, we collected cases between 2006 and 2016 from our center as an external validation set. Clinical features, pathologic characteristics and oncologic outcomes were analyzed. Prognostic factors for overall survival (OS) and breast cancer-specific survival (BCSS) were determined by Cox proportional hazards analyses and were incorporated into the prognostic nomogram. Subgroup analysis based on propensity score matching method was conducted to explore the subset of patients that would benefit from breast-conserving therapy (BCT).ResultsBased on SEER dataset, patients with eTNBC were more likely to undergo mastectomy than BCT. On multivariable analysis, patients with better survival outcomes were those not married, uninsured, had higher T and N stage, and had histological type of mixed invasive ductal and lobular carcinoma. The prognostic nomogram based on these variables successfully predicted the 3- and 5-year BCSS (C-index in training cohort, 0.774; in validation cohort from SEER, 0.768; in validation cohort from our center, 0.723). Subgroup analysis illustrated that patients with T1N0M0 or T2-4N+M0 tumors who underwent BCT achieved longer overall survival than those who underwent mastectomy (for T1N0M0, P = 0.022; for T2-4N+M0, P = 0.003); however, the type of surgery did not influence OS among patients with T1N+M0 or T2-4N0M0 tumors (for T1N+M0, P = 0.305; for T2-4N0M0, P = 0.317).ConclusionsThe prognosis of patients with eTNBC is mainly affected by marital status, insurance status, T stage, N stage and histological type. The prognostic nomogram based on these factors is quite reliable. Subgroup analysis suggested that BCT may be a superior option for patients with eTNBC, especially those with T1N0M0 and T2-4N+M0 tumors.

Abstract Background Cartilage destruction is the main characteristic of osteoarthritis (OA), and osteopontin (OPN) is elevated in OA articular cartilage; however, the reason for the increased OPN level is not determined. In addition, Wnt/β-catenin signaling participates in the progression of OA. The aim of the present study was to evaluate whether canonical Wnt signaling could regulate the expression of OPN in human chondrocytes in vitro. Methods Human chondrocytes were cultured in vitro, and we first assayed the mRNA levels of OPN and β-catenin in chondrocytes. Next, we performed transient transfection of TCF 4 shRNA into chondrocytes to inhibit TCF 4 expression and explore changes in the OPN level. Then, the Wnt/β-catenin signaling inhibitor Dickkopf-1 (Dkk-1) was incubated with chondrocytes, and we assayed the changes in β-catenin and OPN. Results Our results showed that the expression of both β-catenin and OPN was increased in OA chondrocytes, but there were no correlations between β-catenin and OPN expression. TCF4 shRNA downregulated the expression of TCF 4 and OPN in chondrocytes, while after treatment with rDKK-1 at a concentration of 400 ng/ml for 24 h, the mRNA and protein expression of both β-catenin and OPN was significantly decreased in chondrocytes. Conclusions Elevated OPN expression might be regulated by the β-catenin/TCF-4 pathway, and the Wnt/β-catenin inhibitor DKK1 could inhibit the expression of β-catenin and OPN in OA chondrocytes.

Background and Objective: Osteoporosis afflicts a large number of populations in the world and is featured by systemic impairment of bone mass and strength which may further trigger an increase in the risk of fragile fractures. This network meta-analysis (NMA) is designed to distinguish therapies more preferable than others with respect to efficacy and safety. Methods: We searched the medical literature for relevant studies systematically. Both direct and indirect evidence were synthesized to compare the efficacy, described by odds ratios (OR) and 95% credible intervals (CrI). Moreover, the surface under cumulative ranking curve was calculated to rank probabilities with respect to clinical outcomes. The new non-vertebral fractures, hip and wrist fractures, and adverse events were evaluated in this NMA. Results: Patients treated by alendronate, denosumab, teriparatide were associated with a reduced risk of new non-vertebral fractures compared to those treated by placebo. Alendronate, denosumab and zoledronic acid had better efficacy in preventing hip fractures. With respect to wrist fractures prevention, no significant difference was observed. Zoledronic acid exhibited significantly increased risk of adverse events than placebo, alendronate, denosumab, and raloxifene. According to SUCRA, teriparatide ranked highest in new non-vertebral fractures prevention, etidronate and denosumab balanced safety and efficacy well. Conclusion: In summary, teriparatide appeared to be the most efficacious drug for preventing new non-vertebral fractures, while etidronate and denosumab were preferable for balancing safety and efficacy well.

To examine the cross-sectional associations between dietary magnesium (Mg) intake and hyperuricemia (HU).5168 subjects were included in this study. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. Hyperuricemia (HU) was defined as uric acid ≥ 416 μmol/L for male population and ≥ 360 μmol/L for female. A multivariable logistic analysis model was applied to test the associations after adjusting a number of potential confounding factors.The relative odds of the overall prevalence of HU were decreased by 0.57 times in the fourth quintile of Mg intake (OR 0.57, 95% CI 0.35-0.94) and 0.55 times in the fifth quintile (OR 0.55, 95% CI 0.30-1.01) comparing with the lowest quintile, and P for trend was 0.091. The results of multivariable linear regression also suggested a significant inverse association between serum uric acid and Mg intake (β = -0.028, P = 0.022). For male, the relative odds of HU were decreased by 0.62 times in the third quintile of Mg intake (OR 0.62, 95% CI 0.40-0.97), 0.40 times in the fourth quintile (OR 0.40, 95% CI 0.23-0.72) and 0.35 times in the fifth quintile (OR 0.35, 95% CI 0.17-0.71) comparing with the lowest quintile, and P for trend was 0.006. Multivariable adjusted inverse association was also existed between serum uric acid and Mg intake in male population (β = -0.061, P = 0.002). However, no significant association was observed between dietary Mg intake and HU for female.The findings of this cross-sectional study indicated that dietary Mg intake is inversely associated with HU, independent of some major confounding factors. In addition, this association remains valid for the male subgroup, but not for the female subgroup.LevelIII, cross-sectional study.

To examine the cross-sectional associations between dietary magnesium (Mg) intake and radiographic knee osteoarthritis (OA), joint space narrowing (JSN), and osteophytes (OST) respectively.A total of 1626 subjects were included in the study. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. Radiographic knee OA was defined as Kellgren-Lawrence (K-L) Grade 2 in at least one leg. JSN and OST were assessed individually according to the Osteoarthritis Research Society International (OARSI) atlas. A multivariable logistic analysis model was applied to test the various associations after adjusting for potentially confounding factors.The relative odds of radiographic knee OA were decreased by 0.53 times in the third quintile of Mg intake [odds ratio (OR) 0.53, 95% confidence interval (CI) 0.28-1.01], 0.40 times in the fourth quintile (OR 0.40, 95% CI 0.17-0.94) and 0.34 times in the fifth quintile (OR 0.34, 95% CI 0.11-1.00) compared with those in the lowest quintile, while P for trend was 0.111. The relative odds of JSN were decreased by 0.49 times in the third quintile of Mg intake (OR 0.49, 95% CI 0.28-0.88) and 0.37 times in the fifth quintile (OR 0.37, 95% CI 0.14-0.98) compared with those in the lowest quintile, while P for trend was 0.088. There was no significant relationship between dietary Mg intake and the presence of OST.The findings of this cross-sectional study indicate that Mg intake is inversely associated with radiographic knee OA and JSN. It supports potential role of Mg in the prevention of knee OA.LevelIII, cross-sectional study.

Pain represents a major clinical problem and one which has exercised generations of healthcare professionals. Earthworms are used as a traditional Chinese medicine, and have been applied pharmacologically and clinically since a long time in China. However, the analgesic effects of earthworm extract (EE) are seldom studied. Hence, we evaluated the analgesic effects of EE inmice. The obtained data showed that EE increased pain threshold and exhibited peripheral but not central analgesic effects in mice; evidenced by increased inhibition ratio in acetic acid writhing test and formalin test, whereas only slight increase in inhibition ratio in hot plate test and tail immersion test. In addition, EE decreased serum norepinephrine (NE), 5-hydroxytryptamine (5-HT), and nitric oxide (NO) synthase (NOS) concentration, similar to other analgesic drugs like morphine and aspirin. In a nutshell, the obtained data have demonstrated that EE has peripheral analgesic properties and could be used as a promising analgesic drug. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is an aggressive malignant mesenchymal neoplasm amongst adolescents. The aim of the present study was to explore the various modes of action that miR-379 has on the proliferation, migration, and invasion of human OS cells.miR-379 achieves this by targetting eukaryotic initiation factor 4GII (EIF4G2). Human OS cell lines U2OS and MG-63 were selected and assigned into blank, miR-379 mimics, miR-379 mimic negative control (NC), miR-379 inhibitors,miR-379 inhibitor NC, EIF4G2 shRNA, control shRNA, andmiR-379 inhibitor + EIF4G2 shRNA group. The miR-379 expression and EIF4G2 mRNA expression were detected utilising quantitative real-time PCR (qRT-PCR) and the EIF4G2 protein expression using Western blotting. MTT assay, scratch test, Transwell assay, and low cytometry were performed to determine the proliferation, migration, invasion, and cell cycle, respectively. In comparison with the miR-379 mimic NC group, the miR-379 mimics group had decreased EIF4G2 expression; the miR-379 inhibitors group indicated an increased EIF4G2 expression. Compared with the control shRNA group, the EIF4G2 expression was lower in the EIF4G2 shRNA group and the miR-379 expression was dropped in the miR-379 inhibitor + EIF4G2 shRNA group. The proliferation, migration, and invasion abilities of OS cells were reduced in the miR-379 mimics and EIF4G2 shRNA groups. The percentage of OS cells at the G0/G1 stage was increased, and the percentage at the S-stage was decreased in the miR-379 mimics and EIF4G2 shRNA groups.miR-379 may inhibit the proliferation, migration and invasion of OS cells through the down-regulation of EIF4G2. [ABSTRACT FROM AUTHOR]

Background: This study explored the association between single nucleotide polymorphisms (SNPs) in the CD40 gene, rs4810485 G > T and rs1883832 C > T, as well as disease susceptibility and severity in knee osteoarthritis (KOA) in the Chinese Han population.Method: Peripheral venous blood was collected from 133 KOA patients (KOA group) and 143 healthy people (control group) from December 2012 to November 2013. The patients in the KOA group were classified into mild, moderate and severe groups according to disease severity. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to test the genotypes of all subjects. Binary logistic regression analyses were performed to analyze the risk factors for KOA.Results: The KOA group was significantly different from the control group in living environment (P < 0.05). The KOA group had a lower frequency of TT genotype and T allele distribution of rs4810485 G > T compared with the control group, and rs4810485 G > T TT genotype and T allele may associate with low incidence of KOA (all P < 0.05). Besides, T allele and mutant homozygous TT genotype of rs1883832 C > T increased the susceptibility to KOA. Genotype and allele distribution of rs4810485 G > T and rs1883832 C > T were significantly different among the mild, moderate and severe groups (P < 0.05). There were more patients with rs4810485 G > T GG genotype and rs1883832 C > T TT genotype in the severe group than other genotypes of these two SNPs. According to binary logistic regression analysis, rs4810485 G > T TT genotype could alleviate disease severity in KOA, rs1883832 C > T TT genotype increase the severity of KOA and living environment is an important external factor that affects KOA severity.Conclusions: These data provide evidences that rs4810485 G > T and rs1883832 C > T in the CD40 gene may be associated with disease susceptibility and severity in KOA. [ABSTRACT FROM AUTHOR]

Objectives: High-sensitivity C-reactive protein (hsCRP) is possibly related to osteoarthritis (OA) progression and a variety of OA-related symptoms. This study aimed to examine associations between cigarette smoking, betel quid chewing and alcohol consumption and hsCRP in early radiographic knee OA. Design: Cross-sectional health examination survey. Setting: This primary study was conducted in a health examination centre in China. Participants: 936 (656 men and 280 women) patients with early radiographic knee OA were included in this cross-sectional study. Primary and secondary outcome measures: Smoking status was classified into four levels based on daily smoking habit: 0/day, 1-10/day, 11-20/day and >20/day. Betel quid chewing and alcohol consumption status was divided into 'Yes' or 'No'. Early radiographic knee OA was defined as Kellgren Lawrence (K-L) grade 1 or 2 in at least one leg, and elevated hsCRP was assessed as ≥3.0 mg/L. Results: After adjustment for a number of potential confounding factors, a significant positive association between cigarette smoking and hsCRP was observed in the multivariable model. The multivariable-adjusted ORs (95% CI) of elevated hsCRP (≥3.0 mg/L) in the second (1-10/day, n=133), third (11-20/day, n=59) and highest (>20/day, n=104) cigarette smoking categories were 1.54 (95% CI 0.91 to 2.61), 1.27 (95% CI 0.57 to 2.79) and 2.09 (95% CI 1.20 to 3.64), respectively, compared with the non-smoker category (n=640). In addition, there was a positive dose-response relationship between cigarette smoking and elevated hsCRP (p for trend=0.01). No significant associations between betel quid chewing and alcohol consumption and hsCRP were observed in the multivariable model. Conclusions: This study indicated that cigarette smoking was positively associated with serum hsCRP level in patients with early radiographic knee OA. However, in view of the nature of cross-sectional designs, the results need to be confirmed by further prospective studies. [ABSTRACT FROM AUTHOR]

Background: Major reports have suggested that bone mineral density (BMD) is higher in patients with osteoarthritis (OA), while other studies do not agree. Our aim was to examine the cross-sectional association between phalangeal BMD and radiographic knee OA.Methods: A total of 2855 participants were included in this study. Radiographic knee OA was defined as Kellgren-Lawrence (K-L) Grade ≥ 2 in at least one leg. BMD scans of the middle phalanges of the second, third and fourth digits of the nondominant hand were performed with a compact radiographic absorptiometry system (Alara MetriScan®). A multivariable logistic analysis model was applied to test the relation between phalangeal BMD with radiographic knee OA, the presence of knee osteophytes (OSTs), and knee joint space narrowing (JSN) after adjusting for a number of potential confounding factors.Results: The multivariable-adjusted odds ratios with 95 % confidence intervals [ORs (95 % CI)] of radiographic knee OA across phalangeal BMDs were 1.08 (95 % CI 0.89-1.32) and 0.62 (95 % CI 0.45-0.86), respectively. The P for trend was 0.09. For the female population, the multivariable-adjusted ORs (95 % CI) of radiographic knee OA across phalangeal BMD were 1.01 (95 % CI 0.73-1.37) and 0.58 (95 % CI 0.38 - 0.87), respectively. The P for trend was 0.02. This positive finding, however, did not exist in the male subgroup. There was a significantly lower prevalence of OST in the osteoporosis (OP) group than in the normal group (OR = 0.59, 95 % CI 0.40-0.88; P for trend was 0.01). In contrast, the prevalence of JSN was significantly higher in the osteopenia group (OR = 1.22, 95 % CI 1.00-1.48) and the OP group (OR = 1.35, 95 % CI 1.00-1.84) than in the normal group. The P for trend was 0.02.Conclusions: This study observed lower odds for the presence of radiographic knee OA and OST in OP patients than in normal subjects. The prevalence of JSN was higher in the osteopenia and OP groups than in normal subjects. [ABSTRACT FROM AUTHOR]