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Context Fatty acid synthase (FAS) is the only mammalian enzyme to catalyse the synthesis of fatty acid. The expression level of FAS is related to cancer progression, aggressiveness and metastasis. In recent years, research on natural FAS inhibitors with significant bioactivities and low side effects has increasingly become a new trend. Herein, we present recent research progress on natural fatty acid synthase inhibitors as potent therapeutic agents. Objective This paper is a mini overview of the typical natural FAS inhibitors and their possible mechanism of action in the past 10 years (2004-2014). Method The information was collected and compiled through major databases including Web of Science, PubMed, and CNKI. Results Many natural products induce cancer cells apoptosis by inhibiting FAS expression, with fewer side effects than synthetic inhibitors. Conclusion Natural FAS inhibitors are widely distributed in plants (especially in herbs and foods). Some natural products (mainly phenolics) possessing potent biological activities and stable structures are available as lead compounds to synthesise promising FAS inhibitors.

Background Human papillomavirus (HPV) infection is the main cause of precancerous lesions and cervical cancer in women. In order to determine the epidemiological characteristics as well as the relationship between the HPV genotype and cytology test results among women in Beijing, China, we retrospectively collected and analyzed the data from a tertiary hospital in Beijing, China. Methods A total of 21,239 women visited the China–Japan Friendship Hospital between 2014 and 2018 and their cervical exfoliations were collected. Thirteen HPV subtypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68) were examined and ThinPrep cytological test (TCT) was performed. Results Among all cases, 4473 (21.06%) women were infected with HPV. HPV52 (4.64%), HPV16 (4.44%) and HPV58 (4.28%) had higher prevalence. Single-type infection (77.26%) was more common than multiple-type infection (22.74%). Single-type infection was more frequently seen in women aged 50–60 years (17.17%), and multiple-type infection was more common in those aged < 30 years (7.88%). Significant differences in secular trends from 2014 to 2018 were observed for subtypes HPV39, 51, 52 and 58. HPV positive rates of women aged < 30 and 30–40 years changed significantly along with the time period, and the TCT positive rates of women aged 30–40, 40–50, 50–60 and >  60 years also showed significant differences from 2014 to 2018. In addition, 1746 (8.22%) women were TCT positive, of whom, 858 (4.04%), 561 (2.64%) and 327 (1.54%) had atypical squamous cells (ASCs), low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs), respectively. Among four types of cytological lesions, the HPV infection rates were 16.76, 66.08, 63.99 and 85.32% in those negative for intraepithelial lesions or malignancy (NILM), ASC, LSIL and HSIL, respectively. Conclusions HPV52, 16 and 58 are the most common infection subtypes in this study and among four types of cytological lesions, HSILs has the highest HPV prevalence. Significant differences in secular trends are observed for different subtypes in recent 5 years. The results on HPV genotype-specific prevalence should be considered when the HPV vaccine program is implemented in Beijing area.

BackgroudAnti-mitochondrial antibodies (AMAs) can be detected in some idiopathic in ammatory myopathy (IIM) patients. We aimed to investigate the clinical features of IIM patients with AMAs. MethodsWe retrospectively analysed consecutive 1,167 patients with IIM for AMAs-associated myositis and compared them to age-and sex-matched AMA-negative patients. ResultsTwenty-nine patients (2.5%) were identi ed with AMAs-positive myositis; eight of them had primary biliary cholangitis (PBC). There were no signi cant differences in skin rash, dysphagia, interstitial lung disease, and muscle strength between AMAs-positive patients and disease controls. 12/23(52.2%) cases showed immune-mediated necrotizing myopathy (IMNM)-like pathological features. Among AMAs-positive patients, 11 of 16 patients with isolated anti-AMA were classi ed as IMNM which was signi cantly higher than that of patients with coexistent anti-AMAs and myositis-speci c antibodies (p=0.026). Moreover, AMAs-positive patients had a signi cantly higher cardiac involvement ratio (P<0.001) compared to controls. Comparsion in AMAs-positive IIM patients show the incidence of abnormal echocardiography ndings was signi cantly higher in patients without primary biliary cholangitis (PBC) than in patients with PBC(P=0.009). Patients without heart abnormalities took signi cantly less time to achieve disease remission and prednisone tapering to <10 mg than patients with heart abnormalities (P<0.001 and P=0.001, respectively). ConclusionsIMNM was a major histopathological nding in IIM patients with isolated anti-AMAs antibody. AMAs was signi cantly associated with cardiac involvement in IIM. PBC seemed to be a protective factor for abnormal echocardiography ndings in AMAs-positive patients. Patients without heart involvement took less time to achieve disease remission and prednisone tapering off.

IntroductionTumor lymphocyte infiltration is associated with clinical response to chemotherapy in estrogen receptor (ER) negative breast cancer. To identify variants in immunosuppressive pathway genes associated with prognosis after adjuvant chemotherapy for ER-negative patients, we studied stage I-III invasive breast cancer patients of European ancestry, including 9,334 ER-positive (3,151 treated with chemotherapy) and 2,334 ER-negative patients (1,499 treated with chemotherapy).MethodsWe pooled data from sixteen studies from the Breast Cancer Association Consortium (BCAC), and employed two independent studies for replications. Overall 3,610 single nucleotide polymorphisms (SNPs) in 133 genes were genotyped as part of the Collaborative Oncological Gene-environment Study, in which phenotype and clinical data were collected and harmonized. Multivariable Cox proportional hazard regression was used to assess genetic associations with overall survival (OS) and breast cancer-specific survival (BCSS). Heterogeneity according to chemotherapy or ER status was evaluated with the log-likelihood ratio test.ResultsThree independent SNPs in TGFBR2 and IL12B were associated with OS (P <10−3) solely in ER-negative patients after chemotherapy (267 events). Poorer OS associated with TGFBR2 rs1367610 (G > C) (per allele hazard ratio (HR) 1.54 (95% confidence interval (CI) 1.22 to 1.95), P = 3.08 × 10−4) was not found in ER-negative patients without chemotherapy or ER-positive patients with chemotherapy (P for interaction <10−3). Two SNPs in IL12B (r2 = 0.20) showed different associations with ER-negative disease after chemotherapy: rs2546892 (G > A) with poorer OS (HR 1.50 (95% CI 1.21 to 1.86), P = 1.81 × 10−4), and rs2853694 (A > C) with improved OS (HR 0.73 (95% CI 0.61 to 0.87), P = 3.67 × 10−4). Similar associations were observed with BCSS. Association with TGFBR2 rs1367610 but not IL12B variants replicated using BCAC Asian samples and the independent Prospective Study of Outcomes in Sporadic versus Hereditary Breast Cancer Study and yielded a combined HR of 1.57 ((95% CI 1.28 to 1.94), P = 2.05 × 10−5) without study heterogeneity.ConclusionsTGFBR2 variants may have prognostic and predictive value in ER-negative breast cancer patients treated with adjuvant chemotherapy. Our findings provide further insights into the development of immunotherapeutic targets for ER-negative breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0522-2) contains supplementary material, which is available to authorized users.

BackgroundSimilar trends of management and in-hospital mortality of acute pulmonary embolism (PE) have been reported in European and American populations. However, these tendencies were not clear in Asian countries.ObjectivesWe retrospectively analyzed the trends of risk stratification, management and in-hospital mortality for patients with acute PE through a multicenter registry in China (CURES).MethodsAdult patients with acute symptomatic PE were included between 2009 and 2015. Trends in disease diagnosis, treatment and death in hospital were fully analyzed. Risk stratification was retrospectively classified by hemodynamical status and the simplified Pulmonary Embolism Severity Index (sPESI) score according to the 2014 European Society of Cardiology/European Respiratory Society guidelines.ResultsAmong overall 7438 patients, the proportions with high (hemodynamically instability), intermediate (sPESI≥1) and low (sPESI=0) risk were 4.2%, 67.1% and 28.7%, respectively. Computed tomographic pulmonary angiography was the widely employed diagnostic approach (87.6%) and anticoagulation was the frequently adopted initial therapy (83.7%). Between 2009 and 2015, a significant decline was observed for all-cause mortality (from 3.1% to 1.3%, adjusted Pfor trend=0.0003), with a concomitant reduction in use of initial systemic thrombolysis (from 14.8% to 5.0%, Pfor trend<0.0001). The common predictors for all-cause mortality shared by hemodynamically stable and unstable patients were co-existing cancer, older age, and impaired renal function.ConclusionsThe considerable reduction of mortality over years was accompanied by changes of initial treatment. These findings highlight the importance of risk stratification-guided management throughout the nation.

BackgroudAnti-mitochondrial antibodies (AMAs) can be detected in some idiopathic inflammatory myopathy (IIM) patients. We aimed to investigate the clinical features of IIM patients with AMAs.Methods We retrospectively analysed consecutive 1,167 patients with IIM for AMAs-associated myositis and compared them to age- and sex-matched AMA-negative patients. ResultsTwenty-nine patients (2.5%) were identified with AMAs-positive myositis; eight of them had primary biliary cholangitis (PBC). There were no significant differences in skin rash, dysphagia, interstitial lung disease, and muscle strength between AMAs-positive patients and disease controls. 12/23(52.2%) cases showed immune-mediated necrotizing myopathy (IMNM)-like pathological features. Among AMAs-positive patients, 11 of 16 patients with isolated anti-AMA were classified as IMNM which was significantly higher than that of patients with coexistent anti-AMAs and myositis-specific antibodies (p=0.026). Moreover, AMAs-positive patients had a significantly higher cardiac involvement ratio (P<0.001) compared to controls. Comparsion in AMAs-positive IIM patients show the incidence of abnormal echocardiography findings was significantly higher in patients without primary biliary cholangitis (PBC) than in patients with PBC(P=0.009). Patients without heart abnormalities took significantly less time to achieve disease remission and prednisone tapering to <10 mg than patients with heart abnormalities (P<0.001 and P=0.001, respectively).ConclusionsIMNM was a major histopathological finding in IIM patients with isolated anti-AMAs antibody. AMAs was significantly associated with cardiac involvement in IIM. PBC seemed to be a protective factor for abnormal echocardiography findings in AMAs-positive patients. Patients without heart involvement took less time to achieve disease remission and prednisone tapering off.

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