A pulmonary artery was embolized in a patient with an occluded pulmonary vein to manage massive hemoptysis.

BACKGROUND: Stenosis and obliteration of the pulmonary vein can be developed by multiple diseases and might cause hemoptysis. Traditional therapy including surgical procedure and conservative treatments might be inappropriate choices to manage massive hemoptysis. CASE PRESENTATION: A 64-year-old man, diagnosed with advanced stage IVA lung squamous cell carcinoma, presented with dyspnea and recurrent, massive hemoptysis. An initial contrast-enhanced computed tomography revealed a giant tumor in the left lung hilus and occlusion of the left superior pulmonary vein. Despite immediate selective bronchial artery embolization and simultaneous embolization of an anomalous branch of the internal thoracic artery, the massive hemoptysis continued. Subsequently, embolization of the left superior pulmonary artery was performed, achieving functional pulmonary lobectomy, which successfully treated the hemoptysis without relapse during a six-month follow-up. The patient continues to undergo cancer therapy and remains stable. CONCLUSIONS: This case successfully managed massive hemoptysis associated with lung cancer invasion into the pulmonary vein through functional pulmonary lobectomy via embolization of the corresponding pulmonary artery.

The causality between C-reactive protein and asthma: a two-sample Mendelian randomization analysis.

PURPOSE: This study sought to investigate the causal effects of circulating C-reactive protein (CRP) level on risk of asthma and its subtypes by two-sample Mendelian randomization (MR) analysis. METHODS: We utilized single nucleotide polymorphisms (SNPs) associated with both CRP and outcomes of asthma, allergic asthma, and obesity-related asthma as genetic variables via a genome-wide summary association study (GWAS). MR analysis mainly based on the inverse variance weighted (IVW) method was performed to infer the causal relationship between exposure and outcomes. Cochran's Q test and MR-Egger regression analysis were performed to determine respectively the heterogeneity and pleiotropy among instrumental variables (IVs), and leave-one-out analysis was conducted to determine the stability of the MR results. RESULTS: In our study, 42 SNPs were identified as IVs for MR analyses. According to the primary inference results by IVW methods, circulating CRP was demonstrated to be significantly associated with risk of asthma [odds ratio (OR): 1.046; 95% confidence interval (95% CI): 1.004-1.090; P = .030] and obesity-related asthma (OR: 1.072; 95% CI: 1.009-1.138; P = 0.025), whereas no distinct causality with allergic asthma was found (OR: 1.051; 95% CI: 0.994-1.112; P = .081). Sensitivity analyses indicated that there was no horizontal pleiotropy among IVs, and the MR results were proved to be robust by leave-one-out sensitivity analysis, despite the presence of heterogeneity. CONCLUSION: The present study suggested that higher CRP might genetically predict an increased risk of developing asthma and obesity-related asthma, without causality with allergic asthma.

Doubly adaptive biased coin design to improve Bayesian clinical trials with time-to-event endpoints.

Clinical trialists often face the challenge of balancing scientific questions with other design features, such as improving efficiency, minimizing exposure to inferior treatments, and simultaneously comparing multiple treatments. While Bayesian response adaptive randomization (RAR) is a popular and effective method for achieving these objectives, it is known to have large variability and a lack of explicit theoretical results, making its use in clinical trials a subject of concern. It is desirable to propose a design that targets the same allocation proportion as Bayesian RAR and achieves the above objectives but addresses the concerns over Bayesian RAR. We propose the frequentist doubly adaptive biased coin designs (DBCD) targeting ethical allocation proportions from the Bayesian framework to satisfy different objectives in clinical trials with time-to-event endpoints. We derive the theoretical properties of the proposed adaptive randomization design and show through comprehensive numerical simulations that it can achieve ethical objectives without sacrificing efficiency. Our combined theoretical and numerical results offer a strong foundation for the practical use of RAR in real clinical trials.

A Bayesian nonparametric meta-analysis model for estimating the reference interval.

A reference interval represents the normative range for measurements from a healthy population. It plays an important role in laboratory testing, as well as in differentiating healthy from diseased patients. The reference interval based on a single study might not be applicable to a broader population. Meta-analysis can provide a more generalizable reference interval based on the combined population by synthesizing results from multiple studies. However, the assumptions of normally distributed underlying study-specific means and equal within-study variances, which are commonly used in existing methods, are strong and may not hold in practice. We propose a Bayesian nonparametric model with more flexible assumptions to extend random effects meta-analysis for estimating reference intervals. We illustrate through simulation studies and two real data examples the performance of our proposed approach when the assumptions of normally distributed study means and equal within-study variances do not hold.

Numerical study on the characteristics of roadway failure and instability in coal seam with rock parting.

In order to explore the mechanism of rockburst in coal seam with rock parting, a combination of on-site and numerical experiment is used to study the failure and instability process, crack propagation mechanism, and influencing factors. The following four points were addressed: (1) the instability is a process that roadway in coal seam with rock parting go through from stable locking in the initial stress unloading stage to slipping unlocking, and then to spatter ejection in slipping dynamic load disturbance stage. (2) The fracture development caused by unloading excavation of coal seam with rock parting will change from shear crack to tensile crack. In this process, coal-rock contact surface slip and coal-rock fracture are coupled with each other. (3) The greater the mining depth is, the greater the lateral pressure coefficient is, and the higher the rockburst risk is. On the contrary, the lower the risk of rockburst. (4) When choosing the support form of roadway in coal seam with rock parting, the two supporting forms of bolting (cable) and supplementary masonry support should be preferred. The results enrich the theory of the dynamics of surrounding rock fracture in coal mine, further clarify the potential dangers to mining-area roadways and working faces, and provide technical information to ensure the safe and efficient mining of bifurcated coal seam.

[Early effectiveness of computer navigation system-assisted transiliac-transsacral screws placement for posterior pelvic ring injuries].

Objective: To investigate the early effectiveness of transiliac-transsacral screws internal fixation assisted by augmented reality navigation system HoloSight (hereinafter referred to as "computer navigation system") in the treatment of posterior pelvic ring injuries. Methods: A retrospective analysis was made in the 41 patients with posterior pelvic ring injuries who had been treated surgically with transiliac-transsacral screws between June 2022 and June 2023. The patients were divided into navigation group (18 cases, using computer navigation system to assist screw implantation) and freehand group (23 cases, using C-arm X-ray fluoroscopy to guide screw implantation) according to the different methods of transiliac-transsacral screws placement. There was no significant difference in gender, age, body mass index, causes of injuries, Tile classification of pelvic fracture, days from injury to operation, usage of unlocking closed reduction technique between the two groups ( P>0.05). The time of screw implantation, the fluoroscopy times, the guide wire adjustment times of each screw, and the incidence of complications were recorded and compared between the two groups. The position of the transiliac-transsacral screw was scanned by CT within 2 days after operation, and the position of the screw was classified according to Gras standard. Results: The operation was successfully completed in both groups. The time of screw implantation, the fluoroscopy times, and the guide wire adjustment times of each screw in the navigation group were significantly less than those in the freehand group ( P<0.05). There were 2 cases of incision infection in the freehand group, and the incision healed by first intention after active dressing change; there was no screw-related complication in the navigation group during operation and early period after operation; the difference in incidence of complications between the two groups (8.7% vs. 0) was not significant ( P=0.495). According to the Gras standard, the screw position of the navigation group was significantly better than that of the freehand group ( P<0.05). Conclusion: Compared with the traditional freehand method, the computer navigation system assisted transiliac-transsacral screws internal fixation in the treatment of posterior pelvic ring injuries has advantages of improving the accuracy of screw implantation and reducing radiation damage and the time of screw implantation.

A retrospective study of the role of hypercapnia in patients with acromegaly.

BACKGROUND: Acromegaly is a multisystemic disease characterized by an excessive release of growth hormone (GH) and insulin-like growth factor-1. Obstructive sleep apnea (OSA) is a common consequence of acromegaly, and hypercapnia is frequently observed in patients with acromegaly, OSA, and obesity. However, the effects of hypercapnia on acromegaly remain unknown. This study was designed to investigate whether there are differences in clinical symptoms, sleep variables, and biochemical remission after surgery for acromegaly in patients with OSA with or without hypercapnia. METHODS: A retrospective analysis was conducted involving patients with acromegaly and OSA. The pharmacotherapy history for acromegaly before surgery, anthropometric measures, blood gas, sleep monitoring data, and biochemical assays of hypercapnic and eucapnic individuals were collected 1-2 weeks before surgery. Univariate and multivariate logistic regression analyses were performed to determine the risk factors for failed postoperative biochemical remission. RESULTS: In this study, 94 patients with OSA and acromegaly were included. Among them, 25 (26.6%) had hypercapnia. The hypercapnic group had higher body mass index (92% vs. 62.3%; p = 0.005) and poorer nocturnal hypoxemia index. No serological differences were found between the two groups. According to the post-surgery GH level, 52 patients (55.3%) reached biochemical remission. Univariate logistic regression analysis revealed that diabetes mellitus (odds ratio [OR], 2.59; 95% confidence interval [CI], 1.02-6.55), instead of hypercapnia (OR, 0.61; 95% CI, 0.24-1.58), was associated with lower remission rates. Patients who received pharmacotherapy for acromegaly before surgery (OR, 0.21; 95% CI, 0.06-0.79) and had higher thyroid-stimulating hormone levels (OR, 0.53; 95% CI, 0.32-0.88) were more likely to have biochemical remission after surgery. Multivariate analysis further showed that only diabetes mellitus (OR, 3.29; 95% CI, 1.15-9.46) and preoperative pharmacotherapy (OR, 0.21; 95% CI, 0.06-0.83) remained significant. Hypercapnia, hormone levels, and sleep indicators had no effect on biochemical remission after surgery. CONCLUSIONS: Single-center evidence shows that hypercapnia alone may not be a risk factor for lower biochemical remission rates. Correcting hypercapnia does not appear to be required before surgery. More evidence is needed to further support this conclusion.

SCF/c-Kit-activated signaling and angiogenesis require Gαi1 and Gαi3.

The stem cell factor (SCF) binds to c-Kit in endothelial cells, thus activating downstream signaling and angiogenesis. Herein, we examined the role of G protein subunit alpha inhibitory (Gαi) proteins in this process. In MEFs and HUVECs, Gαi1/3 was associated with SCF-activated c-Kit, promoting c-Kit endocytosis, and binding of key adaptor proteins, subsequently transducing downstream signaling. SCF-induced Akt-mTOR and Erk activation was robustly attenuated by Gαi1/3 silencing or knockout (KO), or due to dominant negative mutations but was strengthened substantially following ectopic overexpression of Gαi1/3. SCF-induced HUVEC proliferation, migration, and capillary tube formation were suppressed after Gαi1/3 silencing or KO, or due to dominant negative mutations. In vivo, endothelial knockdown of Gαi1/3 by intravitreous injection of endothelial-specific shRNA adeno-associated virus (AAV) potently reduced SCF-induced signaling and retinal angiogenesis in mice. Moreover, mRNA and protein expressions of SCF increased significantly in the retinal tissues of streptozotocin-induced diabetic retinopathy (DR) mice. SCF silencing, through intravitreous injection of SCF shRNA AAV, inhibited pathological retinal angiogenesis and degeneration of retinal ganglion cells in DR mice. Finally, the expression of SCF and c-Kit increased in proliferative retinal tissues of human patients with proliferative DR. Taken together, Gαi1/3 mediate SCF/c-Kit-activated signaling and angiogenesis.

Implication of a novel measure of obstructive sleep apnea severity for cardiovascular morbidity.

OBJECTIVE: To evaluate the association between cardiovascular morbidity and obstructive sleep apnea (OSA) severity quantified using the sleep breathing impairment index (SBII), a novel measure that captures both respiratory events and event-associated hypoxia. PATIENTS AND METHODS: This retrospective follow-up study included 737 participants with OSA who were diagnosed based on an apnea-hypopnea index of >5/h in polysomnography from January 1, 2012 to December 31, 2015. Data on baseline clinical characteristics and polysomnography parameters were collected. SBII was determined as the sum of products of respiratory events and event-related desaturation areas, and was categorized based on its quintiles. The outcomes were any hospital admission for cardiovascular diseases, including coronary heart disease, stroke, peripheral vascular disease, or heart failure after the diagnosis of OSA. Logistic regression models were constructed to estimate the potential association between SBII and cardiovascular morbidity after adjusting for confounders. RESULTS: A total of 60 cardiovascular events were recorded. Compared with the first quintile of SBII, the odds ratio (95% confidence interval [CI]) of cardiovascular morbidity for the second, third, and fourth quintiles were 4.01 (95% CI, 1.22-13.24), 3.91 (95% CI, 1.05-14.53), and 7.57 (95% CI, 1.70-33.68) after adjusting for covariables, including anthropometric variables, medical conditions, and sleep parameters. CONCLUSION: In patients with OSA, higher SBII was associated with an increased cardiovascular risk. These findings suggest that a more comprehensive measure, such as SBII incorporating the respiratory event and related hypoxia during sleep, may better capture the disease burden and reflect the OSA-associated adverse outcomes.

A genome-wide cross-cancer meta-analysis highlights the shared genetic links of five solid cancers.

Breast, ovarian, prostate, lung, and head/neck cancers are five solid cancers with complex interrelationships. However, the shared genetic factors of the five cancers were often revealed either by the combination of individual genome-wide association study (GWAS) approach or by the fixed-effect model-based meta-analysis approach with practically impossible assumptions. Here, we presented a random-effect model-based cross-cancer meta-analysis framework for identifying the genetic variants jointly influencing the five solid cancers. A comprehensive genetic correlation analysis (genome-wide, partitioned, and local) approach was performed by using GWAS summary statistics of the five cancers, and we observed three cancer pairs with significant genetic correlation: breast-ovarian cancer (r g = 0.221, p = 0.0003), breast-lung cancer (r g = 0.234, p = 7.6 × 10-6), and lung-head/neck cancer (r g = 0.652, p = 0.010). Furthermore, a random-effect model-based cross-trait meta-analysis was conducted for each significant cancer pair, and we found 27 shared genetic loci between breast and ovarian cancers, 18 loci between breast and lung cancers, and three loci between lung and head/neck cancers. Functional analysis indicates that the shared genes are enriched in human T-cell leukemia virus 1 infection (HTLV-1) and antigen processing and presentation (APP) pathways. Our study investigates the shared genetic links across five solid cancers and will help to reveal their potential molecular mechanisms.

RIMeta: An R shiny tool for estimating the reference interval from a meta-analysis.

A reference interval, or an interval in which a prespecified proportion of measurements from a healthy population are expected to fall, is used to determine whether a person's measurement is typical of a healthy individual. For a specific biomarker, multiple published studies may provide data collected from healthy participants. A reference interval estimated by combining the data across these studies is typically more generalizable than a reference interval based on a single study. Methods for estimating reference intervals from random effects meta-analysis and fixed-effects meta-analysis have been recently proposed and implemented using R software. We present an R Shiny tool, RIMeta, implementing these methods, which allows users not proficient in R to estimate a reference interval from a meta-analysis using aggregate data (mean, standard deviation, and sample size) from each study. RIMeta (https://cers.shinyapps.io/RIMeta/) provides users a convenient way to estimate a reference interval from a meta-analysis and to generate the reference interval plot to visualize the results. The use of this web-based R Shiny tool does not require the installation of R or any background knowledge of programming. We explain all functions of the R Shiny tool and illustrate how to use it with a real data example.

The effectiveness of sleep breathing impairment index in assessing obstructive sleep apnea severity.

STUDY OBJECTIVES: Using the apnea-hypopnea index (AHI) and the sleep breathing impairment index (SBII) to assess the severity of obstructive sleep apnea (OSA) to study how effective SBII is in assessing the severity and cardiovascular disease (CVD) prognosis. METHODS: This study comprised a total of 147 patients with diagnosed OSA. The AHI and SBII were calculated from the polysomnography. Patients were enrolled in the cluster analysis using 20 symptoms and the SBII. The prognostic indicator was determined as the moderate-to-high Framingham 10-year CVD risk. RESULTS: Cluster analysis revealed 3 separate groups: cluster 1 (n = 45, 30.61%) had the lowest symptoms complaints yet the highest PSQI score; cluster 2 (n = 70, 47.62%) had considerably increased symptom complaints but the lowest Epworth Sleepiness Scale score, intermediate PSG indices, a higher low arousal threshold possibility, and a lower SBII quantile; cluster 3 (n = 32, 21.77%) had the largest percentage of smokers, a predominant symptom of restless sleep, severe PSG characteristics, a lower low arousal threshold likelihood, a greater SBII quantile and a higher Framingham CVD risk. There were no differences in severity indicated by AHI between groups. Higher SBII rather than AHI is associated with an increased 10-year CVD risk. CONCLUSIONS: SBII provides higher sensitivity when evaluating OSA severity and better predictive capabilities for CVD outcomes. SBII may be a more effective substitute for AHI in the future. CITATION: Dai L, Cao W, Luo J, Huang R, Xiao Y. The effectiveness of sleep breathing impairment index in assessing obstructive sleep apnea severity. J Clin Sleep Med. 2023;19(2):267-274.

The Relationship Between HIF1α and Clock Gene Expression in Patients with Obstructive Sleep Apnea.

Purpose: In this study, we aimed to investigate the precise relationship between hypoxia-inducible factor 1α (HIF1α), circadian clock genes, and OSA. Methods: We recruited 21 patients with OSA and 22 age-matched controls who underwent polysomnography and had their peripheral blood collected on the evening before and the morning after sleep. OSA was defined as an apnea hypopnea index (AHI) ≥15 events/h. Patients in which T90 > 0 were defined as having nocturnal hypoxemia (NH) and were referred to as the NH group. The mRNA levels of HIF1α, HIF1ß and several clock genes (Timeless, Clock, Bmal1, Per1, Per2, Per3, Cry1, Cry2, Ck1δ, Rorα, NR1D1, and NPAS2) were determined by RT-qPCR. The percentage difference in gene expression levels when compared between the morning and evening was then determined as referred to as morning-evening variation (MEV). Results: The MEV for HIF1α mRNA expression in OSA patients increased significantly by 23% (P = 0.008) when compared to patients without OSA. The gene expression levels of Timeless (P = 0.038) and Cry2 (P = 0.012) decreased with AHI. The MEV of Bmal1, Rorα, and HIF1α mRNA levels were upregulated by 16% (P = 0.006), 14% (P = 0.027), and 25% (P = 0.005), respectively, in participants with NH when compared to those without NH. Furthermore, the MEV for HIF1α mRNA levels was positively correlated with the MEV of Bmal1, Cry1, and CK1δ mRNA levels (R = 0.638, P < 0.001; R = 0.327, P = 0.002; R = 0.332, P = 0.001, respectively) and negatively correlated with LSpO2 (R = -0.464, P =0.009) and Mean SpO2 (R = -0.500, P = 0.003). Conclusion: Our data suggest that patients with OSA or NH tend to develop circadian rhythm disorders that may be induced by the hypoxia-mediated augmentation of HIF1α gene expression in OSA.

The Association Between Sleep Breathing Impairment Index and Cardiovascular Risk in Male Patients with Obstructive Sleep Apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is related to multiple complications including insulin resistance (IR), endothelial dysfunction, and increased risk of cardiovascular disease (CVD). The apnea-hypopnea index (AHI) was widely used to measure OSA severity but poorly correlated with complications above. This study aimed to evaluate whether a new metric, the sleep breathing impairment index (SBII), was associated with cardiovascular risk in patients with OSA. METHODS: This study enrolled 140 consecutive male OSA patients without overt atherosclerotic CVD events, including coronary heart disease, stroke, peripheral vascular disease, or heart failure. Data on baseline medical history, anthropometric and polysomnographic parameters, fasting biochemical measurements and endothelial function tests, and common questionnaires were collected. The SBII was calculated by the product of the duration of each obstructive event and the associated desaturation area. The primary outcome was the moderate-to-high Framingham 10-year CVD risk. RESULTS: The median age of enrolled patients was 40 (35-48) years. Eighty subjects had a moderate-to-high Framingham CVD risk. Patients with SBII in the third and fourth quartile had an increased proportion of moderate-to-high Framingham CVD risk with an adjusted OR 6.28 (95% CI 1.10-36.04) and 11.78 (95% CI 1.25-111.38). Significant association was not demonstrated in AHI and the Framingham CVD risk. CONCLUSION: Higher SBII was associated with an increased 10-year CVD risk after adjusting for multiple potential confounding factors. Additional valuable information derived from polysomnography besides AHI deserves to be paid more attention.

New Technique Integrating Hydrate-Based Gas Separation and Chemical Absorption for the Sweetening of Natural Gas with High H2S and CO2 Contents.

Given the drawbacks of the traditional MDEA absorption process, we introduced a hydrate-based gas separation approach. Then, to study the effectiveness of this method, we performed some hydrating experiments demonstrating that energy consumption could be remarkably reduced. However, the acid components (H2S and CO2) in the product gas failed to meet the specification requirements of the sales gas. Consequently, a new technique was developed that integrated hydrate-based gas separation and chemical absorption for the sweetening of natural gas with high H2S and CO2 contents. To evaluate the performance of this new integrated method, technical comparisons based on simulation and experimental data were conducted. The results showed that the new integrated method could effectively remove sour components, which resulted in the product gas being able to meet the sales gas specifications. Additionally, the integrated technique consumed much less energy than the traditional MDEA absorption process and its amine regeneration duty was only 42% that of the MDEA method. What is more, upon an economical evaluation being performed, it was shown that the integrated technique tremendously reduced the investment and operating cost.

Endothelial Function and Arterial Stiffness Should Be Measured to Comprehensively Assess Obstructive Sleep Apnea in Clinical Practice.

Objective: An effective clinical tool to assess endothelial function and arterial stiffness in patients with obstructive sleep apnea (OSA) is lacking. This study evaluated the clinical significance of subclinical markers for OSA management in males without serious complications. Patients/Methods: Males without serious complications were consecutively recruited. Clinical data, biomarker tests, reactive hyperemia index (RHI), and augmentation index at 75 beats/min (AIx75) measured by peripheral arterial tonometry were collected. An apnea hypopnea index (AHI) cutoff of ≥15 events/h divided the patients into two groups. Results: Of the 75 subjects, 42 had an AHI ≥15 events/h. Patients with an AHI ≥15 events/h had higher high-sensitivity C-reactive protein, tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor, and AIx75 values than the control group but no statistical difference in RHI was observed. After controlling for confounders, TNF-α was negatively correlated with the average oxygen saturation (r = -0.258, P = 0.043). RHI was correlated with the rapid eye movement (REM) stage percentage (r = 0.306, P = 0.016) but not with AHI (P > 0.05). AIx75 was positively correlated with the arousal index (r = 0.289, P = 0.023) but not with AHI (r = 0.248, P = 0.052). Conclusions: In males with OSA without severe complications, TNF-α and AIx75 are independently related to OSA. The role of RHI in OSA management requires further elucidation. These markers combined can comprehensively evaluate OSA patients to provide more evidence for the primary prevention of coronary heart disease and treatment response assessment.

Estimating the reference interval from a fixed effects meta-analysis.

A reference interval provides a basis for physicians to determine whether a measurement is typical of a healthy individual. It can be interpreted as a prediction interval for a new individual from the overall population. However, a reference interval based on a single study may not be representative of the broader population. Meta-analysis can provide a general reference interval based on the overall population by combining results from multiple studies. Methods for estimating the reference interval from a random effects meta-analysis have been recently proposed to incorporate the within and between-study variation, but a random effects model may give imprecise estimates of the between-study variation with only few studies. In addition, the normal distribution of underlying study-specific means, and equal within-study variance assumption in these methods may be inappropriate in some settings. In this article, we aim to estimate the reference interval based on the fixed effects model assuming study effects are unrelated, which is useful for a meta-analysis with only a few studies (e.g., ≤5). We propose a mixture distribution method only assuming parametric distributions (e.g., normal) for individuals within each study and integrating them to form the overall population distribution. This method is compared to an empirical method only assuming a parametric overall population distribution. Simulation studies have shown that both methods can estimate a reference interval with coverage close to the targeted value (i.e., 95%). Meta-analyses of women daytime urination frequency and frontal subjective postural vertical measurements are reanalyzed to demonstrate the application of our methods.

Impact of obstructive sleep apnea on cardiovascular risk in patients with acromegaly.

OBJECTIVE: Respiratory complications represented by obstructive sleep apnea (OSA), cardiovascular disease (CVD), and metabolic disorders including insulin resistance (IR) are common in patients with acromegaly. OSA is further associated with a higher risk of IR and CVD in the general population. However, significant information on the effect of OSA on IR and CVD risk for patients with acromegaly remains to be scarce. PATIENTS AND METHODS: This retrospective study included 125 patients with active acromegaly. Medical history, anthropometric parameters, polysomnographic and fasting biochemical measurements were collected. Ten-year Framingham CVD risk scores were calculated and categorized as low, moderate, and high. IR was assessed using the homeostasis model assessment (HOMA-IR). RESULTS: OSA was confirmed in two thirds of the enrolled patients. Compared with patients without OSA, patients with both OSA and acromegaly were found to have higher proportion of HOMA-IR and moderate-to-high 10-year CVD risk. Logistic regression analysis showed that OSA, HOMA-IR, and low-density lipoprotein cholesterol were all risk factors for moderate-to-high CVD risk. Meanwhile, no mediating effect of HOMA-IR in the association between OSA and Framingham CVD risk was observed in patients with acromegaly. CONCLUSIONS: The coexistence of OSA might increase the CVD risk for patients with acromegaly, and IR might independently contribute to CVD risk in acromegalic patients with OSA.

Cigarette smoking enhances the metabolic activation of the polycyclic aromatic hydrocarbon phenanthrene in humans.

Although it is well established that human cytochrome P450 1 family enzymes are induced by cigarette smoking through activation of the Ah receptor, it is not known whether this leads to increased metabolic activation or detoxification of carcinogenic polycyclic aromatic hydrocarbons (PAH), which are present in cigarette smoke and the general environment. We gave oral doses of deuterated phenanthrene ([D10]Phe), a non-carcinogenic surrogate of carcinogenic PAH such as benzo[a]pyrene, to smokers (N = 170, 1 or 10 µg doses) and non-smokers (N = 57, 1 µg dose). Bioactivation products (dihydrodiol and tetraol) and detoxification products (phenols) of [D10]Phe were determined in 6-h urine to obtain a comprehensive metabolic profile. Cigarette smoking increased the bioactivation of [D10]Phe and decreased its detoxification resulting in significantly different metabolic patterns between smokers and non-smokers (P < 0.01), consistent with increased cancer risk in smokers. The Phe bioactivation ratios ([D10]PheT/total [D9]OHPhe) were significantly higher (2.3 (P < 0.01) to 4.8 (P < 0.001) fold) in smokers than non-smokers. With solid human in vivo evidence, our results for the first time demonstrate that cigarette smoking enhances the metabolic activation of Phe, structurally representative of carcinogenic PAH, in humans, strongly supporting their causal role in cancers caused by smoking. The results suggest potential new methods for identifying smokers who could be at particularly high risk for cancer.

Complete mitochondrial genome of Tetraclita squamosa squamosa (Sessilia: Tetraclitidae) from China and phylogeny within Cirripedia.

Here we present the complete mitochondrial genome of Tetraclita squamosa squamosa, which is 15,191 bp in length with 67.20% AT content. It contains 13 protein-coding genes, 2 ribosomal-RNA genes and 22 transfer-RNA genes. All PCGs except nad4l in T. squamosa squamosa start with ATN, and terminated with a complete stop codon, except nad3. Phylogenetic analysis based on mitochondrial PCGs shows that T. squamosa squamosa is clustered with T. serrata into a branch (BP = 100). Our result is consistent with previous reports that genus Tetraclita and family Tetraclitidae are not monophyletic. This study contributes to further phylogenetic analysis within Cirripedia.