Higher risk of osteoporosis in adult-onset asthma than childhood-onset asthma: from genetic and prospective evidence.

Both COA and AOA have a genetically causal effect on osteoporosis. COA and AOA were independently associated with incident osteoporosis, and the risk was greatly higher in AOA. Besides corticosteroids, the increased risk of osteoporosis among asthma patients should be attributed to genetic susceptibility and other asthma medications. PURPOSE/INTRODUCTION: Childhood-onset asthma (COA) differs with adult-onset asthma (AOA) on genetic susceptibility, severity, and co-morbidities. Whether COA or AOA is independently associated with osteoporosis is unexplored. We aimed to determine the effects of COA and AOA on osteoporosis at genetic and individual level. METHODS: We used two-sample Mendelian randomization analysis to explore the causal effects of COA and AOA on osteoporosis. In the UK Biobank cohort, we included 478,289 osteoporosis-free participants at baseline (2006-2010). Participants were classified as non-asthma, COA, and AOA at recruitment. Multivariate Cox regression analysis was used to evaluate the effects of COA, AOA, and multiple asthma medications on incident osteoporosis risk. RESULTS: COA and AOA were causally related to osteoporosis, with odds ratio of 1.007 (95% confidence interval (CI), 1.0003-1.0132) and 1.012 (95% CI, 1.002-1.023), respectively. Multivariate Cox regression analysis suggested that COA (hazard ratio (HR), 1.46; 95% CI, 1.32-1.61) and AOA (HR, 1.70; 95% CI, 1.61-1.80) were independently associated with incident osteoporosis, and the risk was greatly higher in AOA (HR, 1.51; 95% CI, 1.34-1.70). In addition to corticosteroids, monotherapy with leukotriene modifiers (HR, 1.70; 95% CI, 1.20-2.42), long-acting beta agonists (HR, 1.49; 95% CI, 1.18-1.87), and short-acting beta agonists (HR, 1.72; 95% CI1.01-2.93) were independently associated with a higher risk of osteoporosis. CONCLUSIONS: Both COA and AOA have a genetically causal effect on osteoporosis, and the risk of osteoporosis is greatly higher in AOA. Besides corticosteroids, the increased risk of osteoporosis among asthma patients should be attributed to genetic susceptibility and other asthma medications.

Inhibition of FAAH suppresses RANKL-induced osteoclastogenesis and attenuates ovariectomy-induced bone loss partially through repressing the IL17 pathway.

Fatty amide hydrolase (FAAH) is a key degradation enzyme of the endocannabinoid system, mainly responsible for the hydrolysis of arachidonic acid ethanolamine (AEA). Previous investigations have shown that FAAH is involved in a series of biological processes, such as inflammation, immune regulation, and transmembrane signal transduction of neurons. Endogenous cannabinoids and cannabinoid receptors have been reported to participate in the regulation of bone homeostasis by regulating the differentiation of osteoblasts and osteoclasts. We hypothesized that FAAH may play an important role in osteoclastogenesis based on the above evidence. The present study found that the FAAH expression was increased at both mRNA and protein levels during RANKL-induced osteoclastogenesis. Pharmacological and genetic inhibition of FAAH in bone marrow-derived macrophages (BMMs) inhibited osteoclastogenesis, F-actin ring formation, bone resorption, and osteoclast-specific gene expression in vitro. Moreover, intragastric administration of the FAAH inhibitor PF-04457845(PF) ameliorated ovariectomy (OVX)-induced bone loss in mice. Further investigation revealed that nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways were inhibited by PF treatment and FAAH knockdown. RNAseq indicated that the IL17 pathway was blocked by PF, and administration of recombinant murine IL17 protein could partially restore osteoclastogenesis and activate NF-κB and MAPK pathways. To sum up, our findings demonstrate that targeting FAAH could be a promising candidate strategy for treating osteoclast-related diseases, especially osteoporosis.

Gut Clostridium sporogenes-derived indole propionic acid suppresses osteoclast formation by activating pregnane X receptor.

Bone homeostasis is maintained by osteoclast-mediated bone resorption and osteoblast-mediated bone formation. A dramatic decrease in estrogen levels in postmenopausal women leads to osteoclast overactivation, impaired bone homeostasis, and subsequent bone loss. Changes in the gut microbiome affect bone mineral density. However, the role of the gut microbiome in estrogen deficiency-induced bone loss and its underlying mechanism remain unknown. In this study, we found that the abundance of Clostridium sporogenes (C. spor.) and its derived metabolite, indole propionic acid (IPA), were decreased in ovariectomized (OVX) mice. In vitro assays suggested that IPA suppressed osteoclast differentiation and function. At the molecular level, IPA suppressed receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced pregnane X receptor (PXR) ubiquitination and degradation, leading to increased binding of remaining PXR with P65. In vivo daily IPA administration or repeated C. spor. colonization protected against OVX-induced bone loss. To protect live bacteria from the harsh gastric environment and delay the emptying of orally administered C. spor. from the intestine, a C. spor.-encapsulated silk fibroin (SF) hydrogel system was developed, which achieved bone protection in OVX mice comparable to that achieved with repeated germ transplantation or daily IPA administration. Overall, we found that gut C. spor.-derived IPA was involved in estrogen deficiency-induced osteoclast overactivation by regulating the PXR/P65 complex. The C. spor.-encapsulated SF hydrogel system is a promising tool for combating postmenopausal osteoporosis without the disadvantages of repeated germ transplantation.

Mitochondrial pyruvate carrier blockade results in decreased osteoclastogenesis and bone resorption via regulating mitochondrial energy production.

It's widely accepted that increasing mitochondrial respiration plays a pivotal role during osteoclastogenesis. Mitochondrial pyruvate carrier (MPC) is the key transporter that links glycolysis to mitochondrial respiration but little is known about its role during osteoclastogenesis. Our goal was to determine the effects of its blockade on osteoclastogenesis and bone resorption in vivo and in vitro. To address this issue, we performed gene knockdown or pharmacologically inhibited MPC in primary bone marrow-derived monocytes (BMMs) or in an ovariectomized mouse model. We also studied the metabolic changes in RANKL-induced differentiating BMMs with MPC blockade and performed rescue experiments. We found that MPC blockade resulted in decreased osteoclastogenesis both in vivo and in vitro and inhibiting MPC significantly alleviated ovariectomy-induced trabecular bone loss. Further investigations showed that MPC blockade significantly reversed the metabolic profile related to RANK activation, including decreased intermediates involved in citric acid cycle and glutamine metabolism. Moreover, metabolic flux analysis verified that MPC blockade decreased pyruvate flux into TCA cycle with no significant effect on glycolysis. Besides, MPC blockade resulted in suppressed mitochondrial biogenesis in addition to oxidative phosphorylation. Rescue experiments revealed that inhibiting pyruvate dehydrogenase kinase (PDK) via sodium dichloroacetate (DCA), but not targeting glutamine metabolism, could reverse the effects of MPC blockade on osteoclastogenesis. These implied that the effects of MPC blockade were mediated by reduced pyruvate fuel into citric acid cycle in multiple aspects. Taken together, our data demonstrated the inhibitory effects of MPC blockade on osteoclastogenesis, which was mediated by decreased mitochondrial energy production.

α-Mangostin Exhibits a Therapeutic Effect on Spinal Cystic Echinococcosis by Affecting Glutamine Metabolism.

Spinal cystic echinococcosis, a severely neglected, rare disease, is characterized by high morbidity, disability, and mortality in prevalent regions. Due to the high-risk nature of surgical treatment and the ineffectiveness of conventional drugs, there is an unmet need for novel safe and effective drugs for the treatment of this disease. In this study, we examined the therapeutic effects of α-mangostin for spinal cystic echinococcosis, and explored its potential pharmacological mechanism. The repurposed drug exhibited a potent in vitro protoscolicidal effect and significantly inhibited the evolution of larval encystation. Moreover, it demonstrated a remarkable anti-spinal cystic echinococcosis effect in gerbil models. Mechanistically, we found that α-mangostin intervention led to intracellular depolarization of mitochondrial membrane potential and reactive oxygen species generation. In addition, we observed elevated expression of autophagic proteins, aggregation of autophagic lysosomes, activated autophagic flux, and disrupted larval microstructure in protoscoleces. Further metabolite profiling showed that glutamine was imperative for autophagic activation and anti-echinococcal effects mediated by α-mangostin. These results suggest that α-mangostin is a potentially valuable therapeutic option against spinal cystic echinococcosis through its effect on glutamine metabolism.

Inhibition of MAT2A suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss.

Methionine adenosyltransferase II alpha (MAT2A) is the key enzyme to transform methionine and adenosine-triphosphate (ATP) to S-adenosylmethionine (SAM), a general methyl-group donor in vitro. MAT2A has been reported to participate in the NF-κB pathway and maintain the methylated modification, which also affects osteoclastogenesis. In this study, we found the expression of MAT2A was increased upon RANKL stimulation. Pharmacological inhibition of MAT2A by its selective inhibitor AG-270 or genetic silencing by MAT2A-shRNA suppressed osteoclast formation and function in vitro. In vivo treatment with the inhibitor AG-270 also prevented OVX-induced bone loss. Further study revealed that the inhibition of MAT2A affected osteoclast differentiation mainly by suppressing crucial transcription factors and reactive oxygen species induced by RANKL. A quasi-targeted metabolomics assay performed by LC-MS/MS indicated that SAM was reduced by MAT2A knockdown, and the administration of SAM partly rescued the effects of MAT2A inhibition on osteoclastogenesis. These findings revealed that MAT2A is crucial for osteoclastogenesis and might be a potential target for the treatment of osteoporosis attributed to osteoclast dysfunction.

CCAN makes multiple contacts with centromeric DNA to provide distinct pathways to the outer kinetochore.

Kinetochore specification and assembly requires the targeted deposition of specialized nucleosomes containing the histone H3 variant CENP-A at centromeres. However, CENP-A is not sufficient to drive full-kinetochore assembly, and it is not clear how centromeric chromatin is established. Here, we identify CENP-W as a component of the DNA-proximal constitutive centromere-associated network (CCAN) of proteins. We demonstrate that CENP-W forms a DNA-binding complex together with the CCAN component CENP-T. This complex directly associates with nucleosomal DNA and with canonical histone H3, but not with CENP-A, in centromeric regions. CENP-T/CENP-W functions upstream of other CCAN components with the exception of CENP-C, an additional putative DNA-binding protein. Our analysis indicates that CENP-T/CENP-W and CENP-C provide distinct pathways to connect the centromere with outer kinetochore assembly. In total, our results suggest that the CENP-T/CENP-W complex is directly involved in establishment of centromere chromatin structure coordinately with CENP-A.

Differences in the global exposure, mortality and disability of low bone mineral density between men and women: the underestimated burden in men.

Talking about osteoporosis, we tend to focus on post-menopause women who are at increased risk due to estrogen depletion, while less attention has been paid to the disease in men. Currently, there is a lack of understanding about the difference of osteoporosis incidence and burden by sex. In this study, we used data from the Global Burden of Disease Study 2019 (GBD 2019) to compare the difference in the prevalence and burden of low bone mineral density (LBMD) between men and women, by location, year, age and socio-demographic index. We found the prevalence of LBMD was higher in women than in men. However, the age standardized mortality rate was greatly higher in men than in women. Using disability-adjusted life year (DALY) to measure the burden, we also observed higher age standardized DALY rate in men. Using sociodemographic index (SDI) as the measure of social development level, we found that higher mortality and DALY rates were mainly seen in middle and high SDI countries. Falls were the leading cause for of deaths and disabilities in both men and women with LBMD, followed by transport injuries. Fall-related mortality was higher in women, while transport injuries caused more deaths and disabilities in men. Conclusively, more attention should be paid to osteoporosis in men, and related policies, clinical practices, and guidelines are in need to reduce the burden of LBMD and osteoporosis in men.

Incidence, prevalence and disability of spinal cord injury in China from 1990 to 2019: a systematic analysis of the Global Burden of Disease Study 2019.

PURPOSE: We aimed to estimate the incidence, prevalence and years lived with disability (YLDs) of spinal cord injury (SCI) in China in 2019 and temporal trends from 1990 to 2019. METHODS: The Global Burden of Disease Study 2019 was used to obtain data. Outcome measures included age-standardized incidence rate (ASIR), prevalence rate (ASPR) and YLDs rate (ASYR). A Bayesian meta-regression tool, DisMod-MR 2.1, was used to produce the estimates of each value after adjustments. RESULTS: In 2019, there were 234.19 [95% uncertainty interval (UI) 171.84-312.87] thousand incident cases of SCI in China, with an ASIR of 13.87 (95% UI 10.15-18.66) per 100,000. ASIR and ASYR increased by 40.81% (95% UI 32.92-49.14%) and 11.44% (95% UI 5.16-17.29%) compared with 1990, individually. Males had higher ASIR and ASYR in each year from 1990 to 2019, but the incidence and YLDs rates of females exceeded males after 70 years old. Incidence and YLDs rates both ascended with age. SCI at neck level had slightly higher incidence rate but much higher YLDs rate than that below neck level. The average incidence age increased from 38.97 in 1990 to 54.59 in 2019. Falls were the leading cause of SCI. CONCLUSION: The incidence and burden of SCI in China increased significantly during the past three decades. The age structure of SCI patients showed a shift from the young to the elderly as population aging. Urgent efforts are needed to relieve the health pressure from SCI.

What was the Epidemiology and Global Burden of Disease of Hip Fractures From 1990 to 2019? Results From and Additional Analysis of the Global Burden of Disease Study 2019.

BACKGROUND: Hip fractures are associated with a high risk of death; among those who survive a hip fracture, many experience substantial decreases in quality of life. A comprehensive understanding of the epidemiology and burden of hip fractures by country, age, gender, and sociodemographic factors would provide valuable information for healthcare policymaking and clinical practice. The Global Burden of Disease (GBD) study 2019 was a global-level study estimating the burden of 369 diseases and injuries in 204 countries and territories. An exploration and additional analysis of the GBD 2019 would provide a clearer picture of the incidence and burden of hip fractures. QUESTIONS/PURPOSES: Using data from the GBD 2019, we asked, (1) What are the global, regional, and national incidences of hip fractures, and how did they change over a recent 30-year span? (2) What is the global, regional, and national burden of hip fractures in terms of years lived with disability, and how did it change over that same period? (3) What is the leading cause of hip fractures? (4) How did the incidence and years lived with disability of patients with hip fractures change with age, gender, and sociodemographic factors? METHODS: This was a cross-sectional study. Participant data were obtained from the GBD 2019 ( http://ghdx.healthdata.org/gbd-results-tool ). The GBD study is managed by the WHO, coordinated by the Institute of Health Metrics and Evaluation, and funded by the Bill and Melinda Gates Foundation. It estimates the burden of disease and injury for 204 countries by age, gender, and sociodemographic factors, and can serve as a valuable reference for health policymaking. All estimates and their 95% uncertainty interval (UI) were produced using DisMod-MR 2.1, a Bayesian meta-regression tool in the GBD 2019. In this study, we directly pulled the age-standardized incidence rate and years lived with disability rate of hip fractures by location, age, gender, and cause from the GBD 2019. Based on these data, we analyzed the association between the incidence rate and latitude of each country. Then, we calculated the estimated annual percentage change to represent trends from 1990 to 2019. We also used the Spearman rank-order correlation analysis to determine the correlation between the incidence or burden of hip fractures and the sociodemographic index, a composite index of the income per capita, average years of educational attainment, and fertility rates in a country. RESULTS: Globally, hip fracture incidences were estimated to be 14.2 million (95% UI 11.1 to 18.1), and the associated years lived with disability were 2.9 million (95% UI 2.0 to 4.0) in 2019, with an incidence of 182 (95% UI 142 to 231) and 37 (95% UI 25 to 50) per 100,000, respectively. A strong, positive correlation was observed between the incidence rate and the latitude of each country (rho = 0.65; p < 0.001). From 1990 to 2019, the global incidence rate for both genders remained unchanged (estimated annual percentage change 0.01 [95% confidence interval -0.08 to 0.11]), but was slightly increased in men (estimated annual percentage change 0.11 [95% CI 0.01 to 0.2]). The years lived with disability rate decreased slightly (estimated annual percentage change 0.66 [95% CI -0.73 to -0.6]). These rates were standardized by age. Falls were the leading cause of hip fractures, accounting for 66% of all patients and 55% of the total years lived with disability. The incidence of hip fractures was tightly and positively correlated with the sociodemographic index (rho 0.624; p < 0.001), while the years lived with disability rate was slightly negatively correlated (rho -0.247; p < 0.001). Most hip fractures occurred in people older than 70 years, and women had higher incidence rate (189.7 [95% UI 144.2 to 247.2] versus 166.2 [95% UI 133.2 to 205.8] per 100,000) and years lived with disability (38.4 [95% UI 26.9 to 51.6] versus 33.7 [95% UI 23.1 to 45.5] per 100,000) than men. CONCLUSION: Hip fractures are common, devastating to patients, and economically burdensome to healthcare systems globally, with falls being the leading cause. The age-standardized incidence rate has slightly increased in men. Many low-latitude countries have lower incidences, possibly because of prolonged sunlight exposure. Policies should be directed to promoting public health education about maintaining bone-protective lifestyles, enhancing the knowledge of osteoporosis management in young resident physicians and those in practice, increasing the awareness of osteoporosis screening and treatment in men, and developing more effective antiosteoporosis drugs for clinical use. LEVEL OF EVIDENCE: Level III, prognostic study.

Blocking the cytohesin-2/ARF1 axis by SecinH3 ameliorates osteoclast-induced bone loss via attenuating JNK-mediated IRE1 endoribonuclease activity.

cytohesin-2 is a guanine nucleotide exchange factor to activate ARF1 and ARF6, which are involved in various biological processes, including signal transduction, cell differentiation, cell structure organization, and survival. Nevertheless, there is a lack of evidence revealing the role of cytohesin-2 in osteoclast differentiation and in the development of osteoporosis. In this study, we find cytohesin-2 and ARF1 positively regulate osteoclast differentiation and function. Blocking the cytohesin-2 /ARF1 axis with SecinH3 or by genetic silencing of cytohesin-2 inhibits osteoclast formation and function in vitro. In vivo treatment with SecinH3 ameliorates ovariectomy-induced osteoporosis. Mechanistically, RNA-sequencing combined with molecular biological methodologies reveal that the regulatory function of cythohesin-2/ARF1 axis in osteoclast differentiation is mainly dependent on activating the JNK pathway. Further, in addition to the common viewpoint that JNK is activated by IRE1 via its kinase activity, we found that JNK can act upstream and regulate the endoribonuclease activity of IRE1 to promote XBP1 splicing. Both SecinH3 and silencing of cytohesin-2 inhibit JNK activation and IRE1 endoribonuclease activity, leading to the suppression of osteoclast differentiation. Taken together, our findings add new insights into the regulation between JNK and IRE1, and reveal that inhibiting the cytohesin-2/ARF1/JNK/IRE1 axis might represent a potential new strategy for the treatment of post-menopause osteoporosis.

Development and Validation of a Nomogram for Assessing Survival in Patients With COVID-19 Pneumonia.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) has spread worldwide and continues to threaten peoples' health as well as put pressure on the accessibility of medical systems. Early prediction of survival of hospitalized patients will help in the clinical management of COVID-19, but a prediction model that is reliable and valid is still lacking. METHODS: We retrospectively enrolled 628 confirmed cases of COVID-19 using positive RT-PCR tests for SARS-CoV-2 in Tongji Hospital, Wuhan, China. These patients were randomly grouped into a training (60%) and a validation (40%) cohort. In the training cohort, LASSO regression analysis and multivariate Cox regression analysis were utilized to identify prognostic factors for in-hospital survival of patients with COVID-19. A nomogram based on the 3 variables was built for clinical use. AUCs, concordance indexes (C-index), and calibration curves were used to evaluate the efficiency of the nomogram in both training and validation cohorts. RESULTS: Hypertension, higher neutrophil-to-lymphocyte ratio, and increased NT-proBNP values were found to be significantly associated with poorer prognosis in hospitalized patients with COVID-19. The 3 predictors were further used to build a prediction nomogram. The C-indexes of the nomogram in the training and validation cohorts were 0.901 and 0.892, respectively. The AUC in the training cohort was 0.922 for 14-day and 0.919 for 21-day probability of in-hospital survival, while in the validation cohort this was 0.922 and 0.881, respectively. Moreover, the calibration curve for 14- and 21-day survival also showed high coherence between the predicted and actual probability of survival. CONCLUSIONS: We built a predictive model and constructed a nomogram for predicting in-hospital survival of patients with COVID-19. This model has good performance and might be utilized clinically in management of COVID-19.

Inhibition of PFKFB3 suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss.

Osteoclasts are multinucleated cells derived from the monocyte/macrophage cell lineage under the regulation of receptor activator of nuclear factor-κB ligand (RANKL). In previous studies, stimulation by RANKL during osteoclastogenesis was shown to induce a metabolic switch to enhanced glycolytic metabolism. Thus, we hypothesized that blockage of glycolysis might serve as a novel strategy to treat osteoclast-related diseases. In the present study, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), an essential regulator of glycolysis, was up-regulated during osteoclast differentiation. Genetic and pharmacological inhibition of PFKFB3 in bone marrow-derived macrophages suppressed the differentiation and function of osteoclasts. Moreover, intraperitoneal administration of the PFKFB3 inhibitor PFK15 prevented ovariectomy-induced bone loss. In addition, glycolytic activity characterized by lactate accumulation and glucose consumption in growth medium was reduced by PFKFB3 inhibition. Further investigation indicated that the administration of L-lactate partially reversed the repression of osteoclastogenesis caused by PFKFB3 inhibition and abrogated the inhibitory effect of PFK15 on the activation of NF-κB and MAPK pathways. In conclusion, the results of this study suggest that blockage of glycolysis by targeting PFKFB3 represents a potential therapeutic strategy for osteoclast-related disorders.

Pathology of tail fan necrosis in the spiny lobster, Jasus edwardsii.

Tail fan necrosis (TFN) is the bacterial infection of the tail fan of spiny lobsters which leads to melanosis and erosion of the tail fan tissues. The condition is commonly found among spiny lobsters in aquaculture and commercial fisheries, and greatly reduces their commercial value. This study describes the pathology of TFN by examining the tail fans (telson, uropods) and internal organs (mid-gut, hepatopancreas, heart and gill) of 29 affected wild spiny lobsters (Jasus edwardsii) and 14 unaffected in New Zealand. Initial signs of TFN were observed around the margins of lacerations to the tail fan, with more extensive signs extending from these presumptive sites of initiation. The establishment of the condition at points of injury is consistent with the penetration of TFN through the cuticle and tissue layers of the affected tail fans, which is rarely seen in other forms of shell disease. Entry into these tissues was characterised initially by caseous necrosis and haemocyte accumulation, followed by the spread of these responses together with melanisation. Additional pathological changes to the tail fans included pseudomembrane formation, detachment of epidermis or cuticle, clotted haemolymph and fibrosis. Among internal organs, pathological changes were found in a total of two mid-gut, four heart and two gill samples from eight lobsters with TFN, while no suspected changes were found in the organs of lobsters without TFN. The causes of internal organ pathology associated with TFN in spiny lobsters warrants more detailed research.

Immune status of the spiny lobster Jasus edwardsii with tail fan necrosis.

Tail fan necrosis (TFN), a disorder commonly found in some populations of commercially fished and cultured lobsters, is thought to be initiated by injuries caused by handling and containment. The unsightly appearance of affected lobster tails significantly lowers their commercial value. Knowledge about TFN is limited. In this study we describe the morphological features of TFN and apply 6 common methods for evaluating the immune status of wild-caught Australasian red spiny lobsters Jasus edwardsii with and without TFN. The disease was more frequent in uropods than in telsons of the tail fan, and more extensive on the ventral versus the dorsal surfaces of the tail fan. Missing appendages (i.e. antenna, pereiopod or pleopod) were significantly more common and greater in number for individual lobsters affected with TFN versus those without, possibly as a result of handling in the fishery or as an indirect effect of the disease. Two immune parameters, total haemocyte count and phenoloxidase activity in the haemocyte lysate supernatant (HLS), were significantly compromised in lobsters with TFN. No differences were found in the other immune parameters, i.e. haemocyte viability, haemolymph bacterial count and the protein content of haemolymph plasma and HLS. The results are consistent with injury sustained during prior capture and handling that initiates TFN in these natural caught lobsters. These results raise some potential concerns about the fitness of lobsters in natural populations that are affected by TFN, and some potential solutions are proposed.

Phenolic environmental estrogens in urine and blood plasma from women with uterine leiomyoma: Epidemiological survey.

AIM: To explore the effect of phenolic environmental estrogens (EE) on women with uterine leiomyoma (UL). METHODS: Urine and blood plasma samples were collected from 300 patients diagnosed with UL at the Affiliated Zhongda Hospital of Southeast University between December 2013 and December 2014. Control urine and blood plasma samples were collected from 300 women who are either patients without UL or healthy volunteers presenting to the same hospital for physical examination during the same period. Bisphenol A (BPA), nonylphenol (NP) and octylphenol (OP) concentration in these samples was measured using solid phase extraction (SPE) coupled with liquid chromatography-tandem mass spectrometry. RESULTS: The OP concentration in urine and blood plasma was significantly higher in the UL group compared with the control group (r = 0.224, P = 0.001). Urine BPA concentration was not significantly different between the UL group and the control group (r = 0.009, P = 0.896). There was also no statistically significant difference in urine NP concentration between the two groups (r = 0.057, P = 0.419). On logistic regression, exposure concentration of urine BPA (OR, 1.129; 95%CI: 1.081-1.179) and NP (OR, 1.165; 95%CI: 1.025-1.324) was associated with UL genesis (P < 0.05). Nevertheless, there was no significant difference in blood plasma concentration of BPA, OP and NP between the two groups (P > 0.05). CONCLUSION: Urine and blood plasma EE exposure levels in women, especially the urine level, was related to the incidence of UL.