Background Pregnancy-associated breast cancer (PABC) is defined as breast cancer that is diagnosed during pregnancy and/or the postpartum period. Definitions of the duration of the postpartum period have been controversial, and this variability may lead to diverse results regarding prognosis. Moreover, evidence on the dose-response association between the time from the last pregnancy to breast cancer diagnosis and overall mortality has not been synthesized. Methods We systematically searched PubMed, Embase, and the Cochrane Library for observational studies on the prognosis of PABC published up to June 1, 2019. We estimated summary-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs). Subgroup analyses based on diagnosis time, PABC definition, geographic region, year of publication and estimation procedure for HR were performed. Additionally, dose-response analysis was conducted by using the variance weighted least-squares regression (VWLS) trend estimation. Results A total of 54 articles (76 studies) were included in our study. PABC was associated with poor prognosis for overall survival (OS), disease-free survival (DFS) and cause-specific survival (CSS), and the pooled HRs with 95% CIs were 1.45 (1.30-1.63), 1.39 (1.25-1.54) and 1.40 (1.17-1.68), respectively. The corresponding reference category was non-PABC patients. According to subgroup analyses, the varied definition of PABC led to diverse results. The dose-response analysis indicated a nonlinear association between the time from the last delivery to breast cancer diagnosis and the HR of overall mortality (P<0.001). Compared to nulliparous women, the mortality was almost 60% higher in women with PABC diagnosed at 12 months after the last delivery (HR=1.59, 95% CI 1.30-1.82), and the mortality was not significantly different at 70 months after the last delivery (HR=1.14, 95% CI 0.99-1.25). This finding suggests that the definition of PABC should be extended to include patients diagnosed up to approximately six years postpartum (70 months after the last delivery) to capture the increased risk. Conclusion This meta-analysis suggests that PABC is associated with poor prognosis, and the definition of PABC should be extended to include patients diagnosed up to approximately six years postpartum.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver metabolic disease worldwide. Up to 70%–80% of patients with NAFLD were obese, especially abdominal obesity. Many indicators of abdominal obesity have been reported, including waist circumference (WC), visceral obesity index (VAI), lipid accumulation (LAP), and Chinese VAI (CVAI). However, few studies investigated the associations between these indices with NAFLD. This present study aims to explore the associations between abdominal obesity indices with NAFLD. A total of 7,238 participants were involved in the cross-sectional study, and 1,584 participants were included in the longitudinal study from Jidong communities. NAFLD was assessed by abdominal ultrasonography. The trajectory of WC, VAI, LAP, and CVAI during 2013–2016 was identified by a group-based trajectory model. The logistic regression and Cox proportional hazards models analyzed the correlations and causality between abdominal obesity indices with NAFLD. In this study, the prevalence and incidence of NAFLD are approximately 44% and 26%, respectively. In the cross-sectional study, WC, VAI, LAP, and CVAI are associated with NAFLD. After adjustment for potential confounders, the moderate-rising and high-rising groups of CVAI had the highest risk of NAFLD in longitudinal analysis (hazard ratio (HR): 3.903, 95%CI: 2.434–6.259; HR: 5.694 95%CI: 3.098–10.464, respectively). Receiving operating characteristic curves show that CVAI has the best diagnostic value for NAFLD (area under the curve (AUC) = 0.868). CVAI is independently associated with the risk of NAFLD and may also have an important value to the diagnosis of NAFLD.

Osteoarthritis (OA) is a multifactorial disease of the whole joint that has a complex pathogenesis. There is currently no cure for OA. Tofacitinib is a broad JAK inhibitor that can have an anti-in ammatory effect.The objective of this study was to investigate the effect of tofacitinib on the cartilage extracellular matrix in OA and determine whether tofacitinib exerts a protective effect by inhibiting the JAK1/STAT3 signaling pathway and upregulating autophagy in chondrocytes. We established an vitro OA model by exposing SW1353 cells to interleukin-1β (IL-1β) and induced OA in rats using the modi ed Hulth method. We found that IL-1β promoted the expression of OA-related matrix metalloproteinases (MMP-3 and MMP-13), reduced the expression of collagen II, reduced the expression of beclin1 and LC3-II/I, and promoted the accumulation of p62 in SW1353 cells. Tofacitinib attenuated IL-1β-stimulated changes in MMPs and collagen II and restored chondrocyte autophagy. In IL-1β-stimulated SW1353 cells, the JAK1/STAT3 signaling pathway was activated. Tofacitinib inhibited the IL-1β-stimulated expression of p-JAK1 and p-STAT3 and prevented translocation of p-STAT3 to the nucleus. In the rat model of OA, tofacitinib reduced articular cartilage degeneration by delaying cartilage extracellular matrix degradation and increasing chondrocyte autophagy. Our study demonstrates that chondrocyte autophagy was impaired in experimental models of OA. Tofacitinib reduced the in ammatory response and restored the damaged autophagic ux in OA.

ObjectiveStent placement is a feasible approach worldwidely for patients with symptomatic intracranial artery stenosis (sICAS) and hemodynamic impairment (HI) who are at high risk of recurrent stroke after medical treatment. Exploration of factors associated with poor outcomes after stent placement could help develop better individualized therapeutic strategies.MethodsThis study conducted a post-hoc analysis of a prospective, multicenter registry study of stent use for sICAS with HI in China. Patient and clinical demographics, and stenotic lesion images were analyzed using univariate and multivariate Cox regression to the time until any endpoints or the end of the follow-up period. The short-term endpoint included any transient ischemic attack (TIA), stroke, or death within 1 month after stent placement. The long-term endpoints included the short-term endpoints and any TIA or stroke in the region of the affected artery that occurred more than 1 month after stent placement.ResultsTwo hundred and ninety two patients were included, with 13 short-term and 39 long-term endpoints. Multivariate Cox regression analysis revealed that lesions at the arterial origin or bifurcation (Hazard Ratio (HR) = 7.52; 95% CI, 1.89–29.82; p = 0.004) were significantly associated with higher short-term risk. Baseline renal insufficiency reduced the risk (HR = 0.08; 95% CI: 0.01–0.68; p = 0.021). Factors significantly associated with higher long-term risk included irregular or ulcerated plaques at the lesion (HR = 2.15; 95% CI: 1.07–4.33; p = 0.031). Subgroup analyses indicated that higher risk occurred in the older age group (age&gt;59 years, HR = 3.73, 95% CI: 1.27–10.97, p = 0.017), and not in the younger group (age≤59 years, HR = 1.12, 95% CI: 0.42–3.03, p = 0.822).ConclusionIrregular or ulcerated plaques in older patients and lesions at the arterial opening or bifurcation were more likely to result in adverse endpoints for stent placement during long or short -term follow-up. Investigation of these factors might facilitate the development of individualized therapeutic strategies for this population.Clinical Trial Registrationhttp://www.clinicaltrials.gov, identifier: NCT01968122.

Osteoarthritis (OA) is a multifactorial disease of the whole joint that has a complex pathogenesis. There is currently no cure for OA. Tofacitinib is a broad JAK inhibitor that can have an anti-inflammatory effect. The objective of this study was to investigate the effect of tofacitinib on the cartilage extracellular matrix in OA and determine whether tofacitinib exerts a protective effect by inhibiting the JAK1/STAT3 signaling pathway and upregulating autophagy in chondrocytes. We established an vitro OA model by exposing SW1353 cells to interleukin-1β (IL-1β) and induced OA in rats using the modified Hulth method. We found that IL-1β promoted the expression of OA-related matrix metalloproteinases (MMP-3 and MMP-13), reduced the expression of collagen II, reduced the expression of beclin1 and LC3-II/I, and promoted the accumulation of p62 in SW1353 cells. Tofacitinib attenuated IL-1β-stimulated changes in MMPs and collagen II and restored chondrocyte autophagy. In IL-1β-stimulated SW1353 cells, the JAK1/STAT3 signaling pathway was activated. Tofacitinib inhibited the IL-1β-stimulated expression of p-JAK1 and p-STAT3 and prevented translocation of p-STAT3 to the nucleus. In the rat model of OA, tofacitinib reduced articular cartilage degeneration by delaying cartilage extracellular matrix degradation and increasing chondrocyte autophagy. Our study demonstrates that chondrocyte autophagy was impaired in experimental models of OA. Tofacitinib reduced the inflammatory response and restored the damaged autophagic flux in OA.