Piver Type II vs. Type III Hysterectomy in the Treatment of Early-Stage Cervical Cancer: Midterm Follow-up Results of a Randomized Controlled Trial

Introduction: With the expansion of value-based medicine, we explore whether using type III hysterectomy to treat low-risk, early-stage cervical cancer constitutes overtreatment. In present study, we evaluate the midterm safety and postoperative quality of life of patients who underwent type II hysterectomy vs. type III hysterectomy with systematic lymphadenectomy for low-risk early-stage cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) IA2-IB1; maximum tumor diameter < 2 cm).Patients and methods: The main study was a multicenter, phase III, randomized controlled trial (NCT02368574, https://www.clinicaltrials.gov/ct2/show/NCT02368574). Patients meeting the criteria were randomly divided into type II and type III hysterectomy groups between 2015 and 2018. Midterm outcomes were analyzed at 36 months after the first eligible patient was enrolled. The primary end point was disease-free survival, and the secondary end point was postoperative quality of life.Results: A total of 97 patients were preliminarily enrolled, 93 of whom were included in the final analysis. The general information of the two groups did not differ. The 2-year DFS rate in the type II group was 100% compared with 97.9% in the type III group (P > 0.05). Compared to the type III group, the patients who underwent type II hysterectomy showed a shorter surgical time (163 ± 18.8 min vs. 226 ± 16.4 min, P = 0.014), less intraoperative blood loss (174 ± 27.7 ml vs. 268 ± 37.4 ml, P = 0.047), less postoperative urinary retention (5/46 vs. 11/47 cases, P = 0.109), and milder bladder injuries. The postoperative symptom experience scores of the type II group were significantly lower than those of the type III group. Moreover, the postoperative sexual/vaginal functioning and lubrication scores of the type II group were significantly lower than those of the type III group in subgroup analyses of patients who did not undergo postoperative chemoradiotherapy. Sexual apprehension scores were increased postoperatively in both groups.Conclusion: Based on the midterm analysis, the two groups show considerable security within 2 years after surgery, but long-term security requires further analysis. Type II hysterectomy can effectively reduce the surgical time and intraoperative blood loss, decrease postoperative complications, and improve the quality of life of early-stage cervical cancer patients

The Effect of Long-Term or Repeated Use of Antibiotics in Children and Adolescents on Cognitive Impairment in Middle-Aged and Older Person(s) Adults: A Cohort Study

Objectives: We evaluated the effects of long-term/recurrent use of antibiotics in childhood on developing cognitive impairment in middle and old age from UK Biobank Database. Methods: UK Biobank recruited participants aged 37–73 years. Cognitive impairment was ascertained by fluid intelligence questionnaire. Primary outcome was the occurrence of cognitive impairment in middle and old age. Multivariate logistic regression models were used to explore the relationship between long-term/recurrent use of antibiotics and cognitive impairment. Results: Over 3.8–10.8 years’ follow-up, 4,781 of the 35,921 participants developed cognitive impairment. The odds of cognitive impairment in middle and old age among long-term/recurrent use of antibiotics in childhood were increased by 18% compared with their counterparts (adjusted odd ratio 1.18, 95% confidence interval 1.08–1.29, p < 0.01). The effect of long-term/recurrent use of antibiotics in childhood on cognitive impairment was homogeneous across different categories of various subgroup variables such as sex, age, APOE4, ethnic groups, income before tax, smoking status, alcohol status, BMI, hypertension and diabetes but the effect of long-term/recurrent use of antibiotics in childhood was modified by the educational qualification (p-value for interaction <0.05). Conclusion: Long-term/recurrent use of antibiotics in childhood may increase the risk of cognitive impairment in middle and old age

Artemisia pollen allergy in China : Component-resolved diagnosis reveals allergic asthma patients have significant multiple allergen sensitization

Background: Artemisia pollen allergy is a major cause of asthma in Northern China. Possible associations between IgE responses to Artemisia allergen components and clinical phenotypes have not yet been evaluated. This study was to establish sensitization patterns of four Artemisia allergens and possible associations with demographic characteristics and clinical phenotypes in three areas of China. Methods: Two hundred and forty patients allergic to Artemisia pollen were examined, 178 from Shanxi and 30 from Shandong Provinces in Northern China, and 32 from Yunnan Province in Southwestern China. Allergic asthma, rhinitis, conjunctivitis, and eczema symptoms were diagnosed. All patients sera were tested by ImmunoCAP with mugwort pollen extract and the natural components nArt v 1, nArt ar 2, nArt v 3, and nArt an 7. Results: The frequency of sensitization and the IgE levels of the four components in Artemisia allergic patients from Southwestern China were significantly lower than in those from the North. Art v 1 and Art an 7 were the most frequently recognized allergens (84% and 87%, respectively), followed by Art v 3 (66%) and Art ar 2 (48%). Patients from Northern China were more likely to have allergic asthma (50%) than patients from Southwestern China (3%), and being sensitized to more than two allergens increased the risk of allergic asthma, in which cosensitization to three major allergens Art v 1, Art v 3, and Art an 7 is prominent. Conclusions: Componentresolved diagnosis of Chinese Artemisia pollenallergic patients helps assess the potential risk of mugwortassociated allergic asthma.(VLID)329956

Genetics of rheumatoid arthritis contributes to biology and drug discovery

A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological datasets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)1. Here, we performed a genome-wide association study (GWAS) meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ~10 million single nucleotide polymorphisms (SNPs). We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 1012–4. We devised an in-silico pipeline using established bioinformatics methods based on functional annotation5, cis-acting expression quantitative trait loci (cis-eQTL)6, and pathway analyses7–9 – as well as novel methods based on genetic overlap with human primary immunodeficiency (PID), hematological cancer somatic mutations and knock-out mouse phenotypes – to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery

The Mechanisms of Carnosol in Chemoprevention of Ultraviolet B-Light-Induced Non-Melanoma Skin Cancer Formation

© 2018 The Author(s). Carnosol is a natural compound extracted from rosemary and sage, which has been demonstrated to have anti-inflammatory, anti-oxidant, and anti-cancer properties. In this report, we evaluated the therapeutic potential and elucidated the potential mechanism of action of carnosol in chemoprevention of ultraviolet B-light (UVB) induced non-melanoma skin cancer formation. Our data indicated that carnosol could partially reduce UVB-induced reactive oxygen species (ROS) elevation and thus reduce DNA damage. It could also reduce UVB-induced formation of cyclobutane pyrimidine dimers (CDP) in keratinocytes possibly through its ability in absorbing UVB radiation. In addition, carnosol could inhibit the UVB-induced activation of NF-κB and also reduce UVB-induced transformation of keratinocytes. Taken together, the results indicate the role of carnosol as a potential chemopreventive agent upon UVB radiation

A New Delay Vector Integral Inequality and Its Application

<p/> <p>A new delay integral inequality is established. Using this inequality and the properties of nonnegative matrix, the attracting sets for the nonlinear functional differential equations with distributed delays are obtained. Our results can extend and improve earlier publications.</p

Subsequent management and outcomes after first-line PARP inhibitors progression in ovarian cancer patients

Abstract Objectives This retrospective study aims to evaluating the subsequent management and outcomes after first-line PARPi progression in Chinese ovarian cancer population. Methods Clinical and pathologic variables, treatment modalities, and outcomes were assessed. We investigated the subsequent management and outcomes after first-line PARPi progression. The objective response rate (ORR) and disease control rate (DCR) parameters were evaluated to determine the response to subsequent chemotherapy. For the survival analyses, progression-free survival 1 (PFS1), PFS2, overall survival (OS) and PFS2 − PFS1 were analysed. Results A total of 124 patients received PARPi maintenance treatment after first-line chemotherapy during the study period in our center. 44 of them (35.5%) experienced a recurrence. The median duration of PARPi in these patients was 11.1 months (range: 1.2–75.1 months). A total of 40 patients (40/44, 90.9%) received subsequent chemotherapy with 35 (35/44, 79.5%) and 5 (5/44, 11.4%) patients received platinum-based and non-platinum-based chemotherapy in our center. 2 patients (4.5%) received target therapy and other 2 patients (4.5%) received best supportive care. 27.3% (12/44) patients received secondary cytoreduction surgery (SCS). After subsequent chemotherapy, 14 patients received PARPi retreatment as maintenance therapy. In patients who received platinum-based regimens (n = 35), 23 of 35 patients (65.7%) had complete/partial response (CR/PR), 8 of 35 (22.9%) had stable disease (SD), and 4 of 35 (12.1%) had progressive disease (PD). The ORR and DCR of patients who received subsequent chemotherapy was 65.7% and 88.6%, respectively. 15 patients (57.7%, 15/26) were reported to be platinum resistant with a platinum-free interval (PFI)  of < 6 months in patients whose platinum sensitivity of the second line platinum-based regimens was evaluable. Patients who received SCS after PARPi resistant associated with a borderline better PFS2 (median PFS2: 41.9 vs. 29.2 months, P = 0.051) and a non-significantly increased PFS2-PFS1 (median PFS2-PFS1: 12.2 vs. 9.8 months, P = 0.551). Patients with a PFI ≥ 12 months had a significantly better PFS2 (median PFS2: 37.0 vs. 25.3 months, P < 0.001) and a tendency towards a better PFS2-PFS1 than those with a PFI < 12 months (median PFS2-PFS1: 11.2 vs. 8.5 months, P = 0.334). A better PFS2 was observed in patients who received second PARPi maintenance therapy (median PFS2 of 35.4 vs. 28.8 months); however, the difference was not statistically significant (P = 0.200). A better PFS2-PFS1 was observed in patients who received second PARPi maintenance therapy (median PFS2-PFS1: 13.6 vs. 8.9 months, P = 0.002) than those without. Conclusions In summary, some degree of resistance to standard subsequent platinum and non-platinum chemotherapy is noted in the entire cohort. A trend towards higher benefit from subsequent chemotherapy after first-line PARP inhibitors progression was observed in the PFI ≥ 12 months subgroup than those with PFI < 12 months. PARPi retreatment as maintenance therapy and SCS can be offered to some patients with PARPi resistance

Establishing Molecular Subgroups of CD8+ T Cell-Associated Genes in the Ovarian Cancer Tumour Microenvironment and Predicting the Immunotherapy Response

Background: The mechanism by which infiltrating CD8+ T lymphocytes in the tumour microenvironment influence the survival of patients with ovarian cancer (OC) remains unclear. Methods: To identify biomarkers to optimise OC treatment, 13 immune-cell-line-associated datasets, RNA sequencing data, and clinical data from the GEO, TCGA, and the ICGC were collected. Gene expression in OC was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) staining. Results: We identified 520 genes and three immunological clusters (IC1, IC2, and IC3) associated with CD8+ T cells. Higher IFN scores, immune T cell lytic activity, and immune cell infiltration and upregulated expression of immune-checkpoint-related genes indicated that IC3 is more responsive to immunotherapy, whereas IC1 and IC2 have a poorer prognosis. A 10-gene signature, including SEMA4F, CX3CR1, STX7, PASK, AKIRIN2, HEMGN, GBP5, NSG1, and CXorf65, was constructed, and a multivariate Cox regression analysis revealed a significant association between the 10-gene signature-based risk model and overall survival (p < 0.001). A nomogram was constructed with age and the 10-gene signature. Consistent with the bioinformatics analysis, IHC and qRT-PCR confirmed the accuracy of the signatures in OC tissue samples. The predictive ability of the risk model was demonstrated using the Imvigor210 immunotherapy dataset. Conclusions: The development of a novel gene signature associated with CD8+ T cells could facilitate more accurate prognostics and prediction of the immunotherapeutic response of patients with OC