a b s t r a c tStudy Objective: To examine prevalence and risk factors associated with primary dysmenorrhea among Chinese female university students in Hunan province, China. Design: A cross-sectional study. Setting: Female university students in Changsha city, Hunan province, China. Participants: Four thousand six hundred six female individuals selected using a multistage cluster random sampling method. Interventions: A self-administered questionnaire, which included sociodemographic information, lifestyle habits, emotional characteristics, and menstruation pattern, was used to collect data. Main Outcome Measures: Information about menarche, body mass index, cycle length and regularity, primary dysmenorrhea, physical exercise, depression, and anxiety. Results: The prevalence of primary dysmenorrhea was 41.7% (1921/4606) among Chinese female university students. Multivariate binary logistic regression indicated that being a minority (odds ratio [OR], 1.335; 95% confidence interval [CI], 1.083-1.646), underweight (OR, 1.249; 95% CI, 1.08-1.42), annual household income less than 80,000 CNY (OR, 1.169; 95% CI, 1.018-1.342), maternal history of dysmenorrhea (OR, 2.553; 95% CI, 2.236-2.915), age at menarche younger than 12 years (OR, 1.161; 95% CI, 1.013-1.329), irregular menstrual cycle (OR, 1.216; 95% CI, 1.063-1.391), and skipping breakfast (OR, 1.294; 95% CI, 1.124-1.490) were associated risk factors of primary dysmenorrhea. Conclusion: The prevalence of primary dysmenorrhea among Chinese university students is relatively high. Various risk factors were identified that associated with primary dysmenorrhea. More effort and attention should therefore be directed toward this health problem in China.

Long non-coding (lnc) RNAs represent a fascinating class of transcripts that remains highly controversial mainly due to ambiguity surrounding overall biological relevance of these RNAs. Multitude of reverse genetics studies showing functionality of lncRNAs are unfortunately based on assays that are either plagued by non-specific effects and/or cannot unambiguously assign observed phenotypes to the transcript per se. Here, we show application of the novel CRISPR/Cas13 RNA knockdown system that has superior specificity compared to other transcript-targeting knockdown methods like RNAi. We applied this method to a novel widespread subclass of nuclear lncRNAs — very long intergenic non-coding (vlinc) RNAs — in a high-throughput phenotypic assay based on survival challenge in response to anticancer drug treatments. We used multiple layers of controls including mismatch control for each targeting gRNA to ensure uncovering true phenotype-transcript relationships. We found evidence supporting importance for cellular survival for up to 60% of the tested protein-coding mRNAs and, importantly, 64% of vlincRNAs. Overall, this study demonstrates utility of CRISPR/Cas13 as a highly sensitive and specific tool for reverse genetics study of both protein-coding genes and lncRNAs. Furthermore, importantly, this approach provides evidence supporting biological significance of the latter transcripts in anticancer drug response.

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Cell cycle genes are often aberrantly expressed in cancer, but how their misexpression drives tumorigenesis mostly remains unclear. From S phase to early mitosis, EMI1 (also known as FBXO5) inhibits the anaphase-promoting complex/cyclosome, which controls cell cycle progression through the sequential degradation of various substrates. By analyzing 7403 human tumor samples, we find that EMI1 overexpression is widespread in solid tumors but not in blood cancers. In solid cancers, EMI1 overexpression is a strong prognostic marker for poor patient outcome. To investigate causality, we generated a transgenic mouse model in which we overexpressed Emi1. Emi1-overexpressing animals develop a wide variety of solid tumors, in particular adenomas and carcinomas with inflammation and lymphocyte infiltration, but not blood cancers. These tumors are significantly larger and more penetrant, abundant, proliferative and metastatic than control tumors. In addition, they are highly aneuploid with tumor cells frequently being in early mitosis and showing mitotic abnormalities, including lagging and incorrectly segregating chromosomes. We further demonstrate in vitro that even though EMI1 overexpression may cause mitotic arrest and cell death, it also promotes chromosome instability (CIN) following delayed chromosome alignment and anaphase onset. In human solid tumors, EMI1 is co-expressed with many markers for CIN and EMI1 overexpression is a stronger marker for CIN than most well-established ones. The fact that Emi1 overexpression promotes CIN and the formation of solid cancers in vivo indicates that Emi1 overexpression actively drives solid tumorigenesis. These novel mechanistic insights have important clinical implications.

Single-strand breaks (SSBs) represent the major form of DNA damage, yet techniques to map these lesions genome-wide with nucleotide-level precision are limited. Here, we present a method, termed SSiNGLe, and demonstrate its utility to explore the distribution and dynamic changes in genome-wide SSBs in response to different biological and environmental stimuli. We validate SSiNGLe using two very distinct sequencing techniques and apply it to derive global profiles of SSBs in different biological states. Strikingly, we show that patterns of SSBs in the genome are non-random, specific to different biological states, enriched in regulatory elements, exons, introns, specific types of repeats and exhibit differential preference for the template strand between exons and introns. Furthermore, we show that breaks likely contribute to naturally occurring sequence variants. Finally, we demonstrate strong links between SSB patterns and age. Overall, SSiNGLe provides access to unexplored realms of cellular biology, not obtainable with current approaches.

ObjectivesTo explore the prevalence of primary dysmenorrhea (PD), the characteristics of PD and self-care strategies for managing PD among Chinese college girls.DesignCross-sectional study.SettingChangsha, China.ParticipantsA total of 2555 college girls were recruited using multistage cluster random sampling.Outcome measuresA self-report questionnaire was used to measure sociodemographic information, characteristics of PD and self-care strategies for managing PD. Additionally, a Visual Analogue Scale was used to measure pain severity.ResultsOf the 2555 girls, 1306 had experienced PD, representing a 51.1% prevalence. In addition, the prevalence rates of mild, moderate and severe pain in PD were 18.1%, 27.7% and 5.4%, respectively. The most common symptoms associated with PD were cramps (96.9%), weakness (70.0%), backache (65.1%), facial blemishes (55.3%) and irritability (55.3%). Commonly used self-care strategies for managing PD comprised reducing physical activity (94.6%), keeping warm (84.6%), communicating dysmenorrhea with friends or classmates (79.0%), drinking warm beverages (75.7%) and avoiding cold drinks and foods (74.2%). In addition, only 34.8% self-medicated with Western medicine (15.6%), traditional Chinese medicine (8.6%), or both (10.6%). Medical advice was sought by 27.4% of subjects from a Western medical doctor (10.3%), a doctor of traditional Chinese medicine (13.6%), or both (3.5%). Girls who had greater pain severity were more likely to be self-medicated (OR=7.01; 95% CI 4.50 to 10.91), use complementary therapies (OR=2.64; 95% CI 1.70 to 4.10) and seek medical advice (OR=5.93; 95% CI 3.80 to 9.24).ConclusionsPD is highly prevalent among Chinese college girls, with a high burden of symptoms. In addition, these girls are most likely to change their lifestyle, communicate dysmenorrhea with friends or mothers, use heat therapy and engage in self-talk, but less likely to self-medicate or seek medical advice for managing PD.

c Plant-associated bacteria are of great interest because of their potential use in phytoremediation. However, their ability to survive and promote plant growth in metal-polluted soils remains unclear. In this study, a soilborne Cd-resistant bacterium was isolated and identified as Enterobacter sp. strain EG16. It tolerates high external Cd concentrations (Cd 2؉ MIC, >250 mg liter ؊1 ) and is able to produce siderophores and the plant hormone indole-3-acetic acid (IAA), both of which contribute to plant growth promotion. Surface biosorption in this strain accounted for 31% of the total Cd accumulated. The potential presence of cadmium sulfide, shown by energy-dispersive X-ray (EDX) analysis, suggested intracellular Cd binding as a Cd response mechanism of the isolate. Cd exposure resulted in global regulation at the transcriptomic level, with the bacterium switching to an energyconserving mode by inhibiting energy-consuming processes while increasing the production of stress-related proteins. The stress response system included increased import of sulfur and iron, which become deficient under Cd stress, and the redirection of sulfur metabolism to the maintenance of intracellular glutathione levels in response to Cd toxicity. Increased production of siderophores, responding to Cd-induced Fe deficiency, not only is involved in the Cd stress response systems of EG16 but may also play an important role in promoting plant growth as well as alleviating the Cd-induced inhibition of IAA production. The newly isolated strain EG16 may be a suitable candidate for microbially assisted phytoremediation due to its high resistance to Cd and its Cd-induced siderophore production, which is likely to contribute to plant growth promotion. Heavy metal contamination has become one of the most serious environmental problems in recent years. Metal extraction activities are major sources for heavy metals in the environment (1). Cadmium is highly toxic to plants, animals, microorganisms, and humans even at quite low concentrations (2, 3). Although Cd is non-redox active, it can cause oxidative stress by generating reactive oxygen species (ROS) (4), which can lead to DNA damage (5), inhibit the DNA mismatch repair system (6), and disrupt the synthesis of nucleic acids and proteins (7).Phytoremediation, a low-cost and eco-friendly technology for the decontamination of heavy-metal-polluted soils, uses plants to absorb, accumulate, and detoxify heavy metals in soil (3). However, the serious environmental stresses present in most cases of phytoremediation result in slow plant growth, low biomass production, and long time frames for remediation, limiting the usefulness of this technology (8). Beneficial plant-associated bacteria have been shown to protect plants from metal toxicity and promote plant growth. The plant growth-promoting (PGP) characteristics that most of these bacteria possess, including N 2 fixation, siderophore production, the production of plant growth hormones, such as indole-3-acetic acid (IAA), and the reduction of ethylen...

Purpose This study differentiates patient and care delays of breast cancer and explores the related factors as well as the associations with the prognosis in Guangzhou, a southern city of China. Methods A cohort of female incident breast cancer patients (n=1,551) was recruited from October 2008 to March 2012 and followed up until January 1, 2016 (n=1,374) in the affiliated hospitals of Sun Yat-sen University. The factors associated with patient and care delays were analyzed with multivariable logistic models. Cox proportional hazards regression models were constructed to estimate the impacts of the delays on the prognosis. Results There were 40.4% patient delay (≥3 months) and 15.5% care delay (≥1 month). The patient delay, but not the care delay, was significantly related to the clinical stage and consequently worsened the prognosis of breast cancer (hazard ratio, 1.45; 95% confidence interval, 1.09 to 1.91 for progression-free survival). The factors related to an increased patient delay included premenopausal status, history of benign breast disease, and less physical examination. Conclusion Patient delay was the main type of delay in Guangzhou and resulted in higher clinical stage and poor prognosis of breast cancer. Screening for breast cancer among premenopausal women may be an effective way to reduce this delay.