Palladium-Catalyzed Annulative π-Extension of Bay-Iodinated Triphenylenes to Access Polycyclic Aromatic Compounds.

A palladium-catalyzed annulative π-extension reaction of bay-iodinated triphenylenes with aryl iodides/o-chloroaromatic carboxylic acids was developed. This approach enabled the synthesis of diverse polycyclic aromatic compounds, including dibenzo[fg,op]tetracenes, azadibenzo[fg,op]tetracenes, and tribenzo[a,g,m]coronenes. Initial studies indicate that the resulting product, 2,3,8,9,14,15-hexakis(decyloxy)tribenzo[a,g,m]coronene, exhibits good liquid-crystalline properties.

Serum levels of tumor markers and their clinical significance in epithelial ovarian cancer. / ä¸Šçš®æ€§åµå·¢ç™Œè¡€æ¸ ä¸­è‚¿ç˜¤æ ‡å¿—ç‰©æ°´å¹³åŠå ¶ä¸´åºŠæ„ä¹‰ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Tumor markers have been widely used clinically. Detection of serum CA125 is one of the commonly used clinical methods for early screening and early diagnosis of epithelial ovarian cancer, but it is difficult to diagnose epithelial ovarian cancer with a single specific tumor marker. In this study, the combinatorial tumor marker detection method was used to compare the value of each tumor marker alone and different combinations in the diagnosis of epithelial ovarian cancer. METHODS: The clinical data of patients with epithelial ovarian cancer (n=65) and ovarian benign disease (n=29) were collected. Multiple tumor marker protein chip was used to detect cancer antigen 125 (CA125), carbohydrate antigen 242 (CA242), alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (ß-HCG), carcinoembryonic antigen (CEA), cancer antigen 199 (CA199), neuron-specific enolase (NSE), Ferritin, cancer antigen 153 (CA153), and human growth hormone (HGH) serum levels, and to compare the differences between the benign and malignant ovarian tumors. The correlation between tumor markers and clinicopathologic features for ovarian epithelial carcinoma was analyzed by χ2 test. Spearman rank analysis showed the correlation between CA125 expression level and other tumor markers in epithelial ovarian cancer and the correlation between age and the above 10 tumor markers. Sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and diagnostic efficiency were used to evaluate the diagnostic value of single tumor marker and the combination of tumor markers. RESULTS: The levels of ß-HCG, NSE, CA153, and CA125 in the epithelial ovarian cancer group were higher than those in the ovarian benign disease group. The level of NSE in the serum of patients with epithelial ovarian cancer was related to the clinical stage of patients. In addition, the levels of CA242, ß-HCG, CEA, NSE, Ferritin, CA153 in the serum of patients with epithelial ovarian cancer were positively correlated with CA125 (rs=0.497, P<0.001; rs=0.612, P<0.001; rs=0.358, P=0.003; rs=0.680, P<0.001; rs=0.322, P=0.009; rs=0.609, P<0.001, respectively), and the levels of ß-HCG, Ferritin, CA153 were positively correlated with the patient's age (rs=0.256, P=0.040; rs=0.325, P=0.008; rs=0.249, P=0.046, respectively). In the diagnosis of epithelial ovarian cancer, the sensitivity, Youden index, and diagnostic efficiency of CA125 detection alone were higher than the results of the other 9 separate detections. When CA153, CA199, CA242, Ferritin, and CEA were combined with CA125, the sensitivity of the combined detection of different combinations was higher than that of CA125 alone. The combined detection sensitivities of CA125+CEA and CA125+Ferritin+CEA were 89.2% and 90.8%, respectively, and the diagnostic efficiencies were both 84.1%, which were higher than those of other combinations. The Youden index of CA125+CEA joint detection was 0.616, which was higher than those of other combinations. CONCLUSIONS: CA125 has a high diagnostic value in the diagnosis of epithelial ovarian cancer. The detection of combined tumor markers in serum has higher sensitivity and specificity in epithelial ovarian cancer.

Palladium-catalyzed annulative π-extension of o-halobiphenyls with o-chloropyridinecarboxylic acids to access azatriphenylenes.

A palladium-catalyzed bay-region annulative π-extension reaction of o-halobiphenyls with o-chloropyridinecarboxylic acids was developed. The reaction was carried out with a 1 : 1 ratio of substrates. A variety of azatriphenylene derivatives could be synthesized by this approach. This transformation could be applied to the synthesis of ionic liquid-crystalline molecules.

ß-Caryophyllene induces apoptosis and inhibits cell proliferation by deregulation of STAT-3/mTOR/AKT signaling in human bladder cancer cells: An in vitro study.

The current study aimed to explore the antitumor effect of ß-caryophyllene (BCP) on two different cell lines of T24 and 5637 human bladder cancer (BC) cells and its potential molecular mechanisms in inhibition of STAT-3/mTOR/AKT signaling pathways and the inductive process of apoptosis mechanism. The results indicated that BCP showed significant cytotoxicity in BC T24 and 5637 cells in a dose- and time-dependent manner, and IC50 values were 40 µg/ml in the BC cells T24 and 5637. Reactive oxygen species (ROS) synthesis and apoptosis induction were significantly developed, but the mitochondrial membrane potential (Δψm) decreased on BCP treatment as detected by the fluorescence method. Moreover, cell migration was markedly reduced in BCP and Bax, Bcl-2 mRNA expression was modified. Finally, it was found that the STAT-3, mTOR, and AKT protein expressions were suppressed via inhibition of cytotoxicity in T24 and 5637 cells. Therefore, we finally concluded that BCP is an effective treatment against BC T24 and 5637 cells, and it has great chemotherapeutic potential for further bladder carcinoma treatment.

Recommendations for determining the validity of consumer wearable and smartphone step count: expert statement and checklist of the INTERLIVE network.

Consumer wearable and smartphone devices provide an accessible means to objectively measure physical activity (PA) through step counts. With the increasing proliferation of this technology, consumers, practitioners and researchers are interested in leveraging these devices as a means to track and facilitate PA behavioural change. However, while the acceptance of these devices is increasing, the validity of many consumer devices have not been rigorously and transparently evaluated. The Towards Intelligent Health and Well-Being Network of Physical Activity Assessment (INTERLIVE) is a joint European initiative of six universities and one industrial partner. The consortium was founded in 2019 and strives to develop best-practice recommendations for evaluating the validity of consumer wearables and smartphones. This expert statement presents a best-practice consumer wearable and smartphone step counter validation protocol. A two-step process was used to aggregate data and form a scientific foundation for the development of an optimal and feasible validation protocol: (1) a systematic literature review and (2) additional searches of the wider literature pertaining to factors that may introduce bias during the validation of these devices. The systematic literature review process identified 2897 potential articles, with 85 articles deemed eligible for the final dataset. From the synthesised data, we identified a set of six key domains to be considered during design and reporting of validation studies: target population, criterion measure, index measure, validation conditions, data processing and statistical analysis. Based on these six domains, a set of key variables of interest were identified and a 'basic' and 'advanced' multistage protocol for the validation of consumer wearable and smartphone step counters was developed. The INTERLIVE consortium recommends that the proposed protocol is used when considering the validation of any consumer wearable or smartphone step counter. Checklists have been provided to guide validation protocol development and reporting. The network also provide guidance for future research activities, highlighting the imminent need for the development of feasible alternative 'gold-standard' criterion measures for free-living validation. Adherence to these validation and reporting standards will help ensure methodological and reporting consistency, facilitating comparison between consumer devices. Ultimately, this will ensure that as these devices are integrated into standard medical care, consumers, practitioners, industry and researchers can use this technology safely and to its full potential.

Dosimetric verification of stereotactic body radiotherapy treatment plan via ArcCHECK-3DVH system. / ArcCHECK-3DVH系统在体部立体定向放射治疗剂量验证中的应用.

OBJECTIVES: To study the feasibility of ArcCHECK-3DVH system in dosimetric verification for stereotactic body radiaotherapy (SBRT) with flattening filter free (FFF) model. METHODS: SBRT treatment plans for 57 patients were introduced into ArcCHECK phantom and recalculated. The calculated dose distribution of treatment planning system and the measured dose distribution of ArcCHECK phantom were compared by γ analysis. Then the 3 dimensional dose distribution of target and organs at risk was reconstructed by 3DVH software. The reconstructed dose and calculated dose with treatment planning system (TPS) were compared, and the dose volume γ pass rate and deviation of dose volume parameters to the target and organs at risk were quantitatively valuated. RESULTS: Based on the threshold criteria (3%, 3 mm, 10%), namely the deviation of measuring points between the planned value and the measured value was less than 3%, and the proportion of points with similar values in the plane or sphere with the center of the point and the radius of 3 mm was 10%, the relative and absolute dose pass rates of SBRT treatment plans in ArcCHECK system via γ analysis were greater than 95%. Based on the stricter threshold criteria (2%, 2 mm, 10%), the relative and absolute dose pass rates of SBRT treatment plan in ArcCHECK system via γ analysis were about 93%. In 3DVH dose verification, the γ pass rate of target and organs at risk was exceed 97%, and the deviations in 3DVH of the target and organs at risk were less than ±5%. CONCLUSIONS: The ArcCHECK-3DVH system in dose verification can provide more comprehensive dose distribution information to reasonably evaluate the SBRT plan, with more significance for guiding clinical treatment.

Romidepsin (FK228) in a Mouse Model of Lipopolysaccharide-Induced Acute Kidney Injury is Associated with Down-Regulation of the CYP2E1 Gene.

BACKGROUND Romidepsin (FK228) or depsipeptide, is a selective inhibitor of histone deacetylase 1 (HDAC1) and HDAC2. This study aimed to investigate the effects and molecular mechanisms of romidepsin (FK228) in a mouse model of acute kidney injury (AKI) induced by lipopolysaccharide (LPS). MATERIAL AND METHODS The mouse model of AKI was developed by intraperitoneal injection of LPS. The mice were also treated intraperitoneally with romidepsin (FK228) six hours following injection of LPS. Markers of renal injury were measured, including blood urea nitrogen (BUN), serum creatinine (SCR), and serum cystatin C (Cys C) were measured. Histology and transmission electron microscopy were performed to evaluate tissue injury further. Levels of HDACs were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) assays were used to investigate the regulation of CYP2E1 expression. RESULTS Treatment with romidepsin (FK228) significantly reduced the levels of BUN, SCR, and Cys C induced by LPS. Histology of the mouse kidneys showed that treatment with romidepsin (FK228) reduced the degree of renal injury. CYP2E1 significantly reduced following treatment with romidepsin (FK228) in the mouse model of AKI. Also, acetylation of H3 was upregulated following treatment with romidepsin (FK228), and binding of hepatocyte nuclear factor-1 alpha (HNF-1a) on the CYP2E1 promoter was significantly increased. CONCLUSIONS In a mouse model of LPS-induced AKI, treatment with romidepsin (FK228) downregulated the expression of CYP2E1 by inhibiting the binding if HNF-1a with the CYP2E1 promoter to reduce renal injury.

ACTN3 is associated with children's physical fitness in Han Chinese.

The ACTN3 gene locates on 11q13-q14 and encodes the α-actinin-3 protein, which is only expressed in human skeletal muscle and influenced muscle function and metabolism. The previous studies reported that SNP rs1815739 is associated with elite power athletes' performance. In this study, we investigated the association between five SNPs within the ACTN3 gene and Chinese children physical fitness. We recruited 2244 Han Chinese children participants, and measured their 25-m run, stand broad jump, 10-m shuttle run, handgrip, BMI (calculated by weight and height) data. SNPs rs1671064, rs2275998, rs2290463, rs10791881, and rs1815739 of ACTN3 gene were genotyped and analyzed in five physical fitness data. QTL analysis on genotype and physical fitness data was carried out in all samples. Furthermore, a dichotomous division of samples into an overweight group (543) and a normal group (1701) was used for an association study of overweight. In the QTL analysis, we found rs2290463 was significantly associated with stand broad jump (corrected P value = 0.009, beta = 2.692). After added age and gender as covariates in the regression test, the association became more significant (P value = 5.80 × 10- 5, corrected P value = 4.06 × 10- 4); when we used BMI as a covariate, the association still existed (P value = 4.65 × 10- 4, corrected P value = 0.001). In the association study of overweight, rs2275998 was found to be significant (OR, 95% CI = 0.733 [0.6-0.895]; Pallele = 0.011, Pgenotype = 0.024) after the Bonferroni correction, and the association did not change much after a further correction for gender, age, and stand broad jump performance. Our results showed that common variants in ACTN3 are significantly associated with both stand broad jump performance and overweight in Han Chinese children.

Polymorphism of the PPARD Gene and Dynamic Balance Performance in Han Chinese Children.

BACKGROUND: Athletic performances are complex traits with heritability of ~66%. Dynamic balance is one of the most important athletic performances, and there has been little studies for it in sports genomics. The candidate PPARD gene was reported to be able to affect muscle development for balance predisposition and influence the athletic performance including skiing triumph in the Caucasian population. This study aims to investigate whether the PPARD gene is a susceptibility gene for dynamic balance performance in Han Chinese children. RESULTS: A total 2244 children were recruited and their balance beam performances were measured. Five polymorphisms in the PPARD gene were genotyped through the MassARRAY Sequenom platform. Rs2016520 exerted significant association with dynamic balance performance (minor allele C, P = 0.015, Pcorrected < 0.05) and was affirmed in a meta-analysis by combining previously reported Caucasian cohorts (OR = 1.57, 95% CI = [1.30, 1.91], P < 10 -5) . Another polymorphism, rs2267668, was also significantly associated with dynamic balance performance (minor allele G, P = 0.015, Pcorrected < 0.05). In the dichotomous study, 321 cases (61% boys and 39% girls) and 370 controls (49% boys and 51% girls) in our samples were selected as representatives, and the thresholds were the mean velocity (0.737 m/s) ± standard deviation (0.264 m/s), in which rs2016520-C and rs2267668-G still remained significant (CI =1.41 [1.11~1.79], P = 0.004, Pcorrected < 0.016; CI =1.45 [1.14~1.86], P = 0.002, Pcorrected < 0.016). In different genders, consistent OR direction was observed for each variant. CONCLUSIONS: Our results suggested that the PPARD gene is associated with dynamic balance performance of human being, and further studies to reveal its etiology is strongly suggested.

[Dosimetric verification of flattening filter free model based on TrueBeam accelerator using ArcCheck system].

OBJECTIVE: To study the feasibility of ArcCheck verification system in dosimetric verification for stereotactic radiotherapy (SRT) the stereotactic radiotherapy (SRT) with flattening filter free (FFF) model.
 Methods: A total of 76 cases under SRT treatment plans were introduced into ArcCheck phantom and recalculated. Threshold criteria was set as (3%, 3 mm, 10%) or (2%, 2 mm, 10%). The calculated dose distribution and the measured dose distribution of ArcCheck phantom were compared by means of distance to agree (DTA) and Gamma analysis method respectively.
 Results: Based on the threshold criteria (3%, 3 mm, 10%), the relative and absolute mean pass rates of SRT treatment plans by DTA and Gamma analysis were greater than 95%. Based on the threshold criteria (2%, 2 mm, 10%), the relative and absolute mean pass rates of SRT treatment plan by DTA and Gamma analysis were about 90%. The dose pass rate of Gamma analysis method was slightly higher than that of DTA analysis method (P<0.001).
 Conclusion: The ArcCheck verification system is a rapid and accurate method for SRT dose verification, and discrepancies are found in different analysis methods.

The diagnostic performance of 18F-DCFPyL PET in patients with suspected prostate cancer: A systemic review and meta-analysis.

Introduction: Our meta-analysis aimed to evaluate the diagnostic value of 18F-DCFPyL prostate-specific membrane antigen (PSMA) PET in patients with suspected prostate cancer. Methods: We searched for articles that evaluate the diagnostic value of 18F-DCFPyL PSMA PET in patients with suspected prostate cancer in PubMed, Embase, Cochrane Library, and Web of Science until 1 August 2022. Using the QUADAS-2 instrument, two researchers independently assessed the effectiveness of the studies that were included. The four-grid table data were analyzed by Meta-disc1.4 and Stata 16.0 software. The heterogeneity of each study was tested. Results: A total of five studies with 258 patients were included, and the pooled sensitivity and specificity of 18F-DCFPyL PSMA PET for primary prostate cancer were 0.92 (95% confidence interval (CI): 0.85-0.96) and 0.59 (95% CI: 0.08-0.96), respectively. 18F-DCFPyL PSMA PET was successful in detecting primary prostate cancer, with an area under the curve (AUC) of 0.92 (95% CI: 0.89-0.94). Conclusions: 18F-DCFPyL PSMA PET has a strong predictive value for primary prostate cancer and is an effective method for the non-invasive diagnosis of prostate cancer. More prospective articles were needed.

SOX8 Knockdown Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer by Inhibiting the Notch Signaling Pathway.

Castration-resistant prostate cancer (CRPC) is still challenging to treat. Dissatisfaction with androgen signal-targeted therapy forces people to look for other treatment strategies. Therefore, this study is aimed at exploring the role of SOX8/Notch signaling in CRPC. The upregulation of SOX8, Notch4, and Hes5 indicated a poor progression-free survival (PFS) in CRPC patients. The expression of these proteins was also upregulated in enzalutamide-resistant LNCaP cells (Enza-R). Moreover, knocking down SOX8 inhibited malignant biological behaviors and decreased the activation of Notch signaling in Enza-R cells. Importantly, knocking down SOX8 obviously reversed the enzalutamide resistance in Enza-R cells, while RO0429097 (a γ secretase inhibitor inactivates Notch signaling) exerted similar effects. At last, we found that both SOX8 knockdown and/or RO0429097 suppressed tumor growth and bone metastasis in vivo. Altogether, our study indicated that the SOX8/Notch signaling is involved in CRPC and that these enzymes are possible targets to develop novel treatment for CRPC.

[The relationship between anaphylatoxin C3a and benign prostatic hyperplasia with inflammation].

OBJECTIVE: To study the relationship of anaphylatoxin C3a level in expressed prostatic secretions (EPS) with prostate tissue inflammation in BPH. METHODS: This study included 40 BPH patients receiving TURP operational therapy in West China Hospital during September, 2009 to March, 2010. For each patient, IPSS and NIH-CPSI were evaluated, serum PSA levels, prostatic volume and urine WBC were measured. EPS was collected before operation for the test of C3a level, while EPS also was obtained from 10 healthy men as normal control. Prostatic tissue was collected by the operation and histological inflammation was investigated by histopathological study. RESULTS: C3a levels in EPS of the BPH patients: severe inflammation group > mild inflammation group > normal control group (all P < 0.01). C3a levels in the EPS could be used to determine whether BPH combined inflammation, sensitivity : 0.97, specificity: 0.70. C3a levels in EPS was not relevant with PSA, fPSA levels, age, BMI, prostate volume or urine WBC levels; but NIH-CPSI was correlated (r = 0.495, P < 0.01). C3a in EPS of retained catheter group was more than non-catheter group significantly (P < 0.05). CONCLUSION: C3a is an ideal criteria to diagnose prostatic histological inflammation in BPH patients. There is no convincing evidence to correlate C3a in EPS with serum PSA levels, BMI, age, prostatic volume and urine's WBC. Excessively high C3a levels and the NIH-CPSI, indwelling have correlations.

Systematic Evaluation for the Influences of the SOX17/Notch Receptor Family Members on Reversing Enzalutamide Resistance in Castration-Resistant Prostate Cancer Cells.

The treatment of castration-resistant prostate cancer (CRPC) remains challenging due to the failure of androgen deprivation therapy (ADT); hence the search for other molecular therapeutic targets besides androgen receptor signaling is ongoing. This study systematically investigated the expression of SOX17 and Notch receptors in CRPC tissues and cells in vitro, showing that consistent clinical CRPC, SOX17/Notch1, and Notch4 were responsible for enzalutamide resistance in CRPC cells. The γ secretase inhibitors, BMS-708163, GSI-IX, PF-3084014, and RO4929097 abrogated the enzalutamide resistance by inhibiting Notch1 or/and Notch4 in vitro, with GSI-IX and RO4929097 being more effective than BMS-708163 and PF-3084014 in reliving bone metastasis in vivo. In conclusion, the Notch1 and Notch4 inhibitors GSI-IX and RO4929097 are promising therapeutic agents for the treatment of CRPC.

MicroRNA-151 regulates the growth, chemosensitivity and metastasis of human prostate cancer cells by targeting PI3K/AKT.

PURPOSE: Prostate cancer causes significant mortality and microRNAs (miRs) have been shown to regulate the growth and metastasis of different cancers. In this context, the present study was designed to investigate the potential of miR-151 in the treatment of prostate cancer. METHODS: The normal and the prostate cancer cell lines (LNCaP, PC-3 and Du-145) were used in this study. The expression of miR-151 was determined by qRT-PCR. The DAPI and annexin V/propidium iodide (PI) staining were used for the detection of apoptosis. Transwell assay was used for the estimation of cell migration and invasion. Western blot analysis was used for the determination of the protein expression. RESULTS: miR-151 was downregulated in prostate cancer cells and showed inhibitory effect on cell growth which was manifested as decline in cell survival and loss of viability of cancer cells. Additionally, the chemosensitivity of prostate cancer cells to 5-FU was enhanced under miR-151 overexpression. Furthermore, miR-151 also inhibited the migration and invasion of cancer cells. The results of western blot analysis showed that miR-151 overexpression blocks the Pi3K/AKT signalling pathway in prostate cancer cells. CONCLUSION: Taken together, miR-151 has growth inhibitory effect against prostate cancer and negatively regulates the cell migration and invasion along with enhancement of chemosensitivity of cancer cells.

Association of urinary incontinence and depression or anxiety: a meta-analysis.

OBJECTIVE: We explored the relationship between urinary incontinence (UI) and depression or anxiety. METHODS: We searched the Cochrane Library, Embase, and PubMed for articles on the association between depression, anxiety, and UI. We calculated pooled 95% confidence intervals (CIs) and odds ratios (ORs). RESULTS: Twelve articles (31,462 participants) were included. The UI group had significantly higher depression and anxiety levels than the non-UI group (OR = 1.73, 95%CI: 1.64-1.82, I2 = 75.5%). In subgroup analysis, depression and anxiety were significantly higher in participants with UI than in those without UI (OR = 1.95, 95%CI: 1.82-2.10, I2 = 64.3% and OR = 1.54, 95%CI: 1.43-1.65, I2 = 59.2%, respectively). In subgroup analysis by age, participants with UI had significantly higher depression and anxiety, regardless of age, than the non-UI group (OR = 1.59, 95%CI: 1.29-1.95, I2 = 59.1% and OR = 1.98, 95%CI: 1.62-2.43, I2 = 75.5%, respectively). CONCLUSION: Patients with UI had significantly higher depression and anxiety levels than those without UI. Depression and anxiety were higher in patients with UI than in those without UI, regardless of age. Larger sample sizes and more high-quality studies are needed to validate our findings.

Glutathione-S-transferases M1/T1 gene polymorphisms and male infertility risk in Chinese populations: A meta-analysis.

BACKGROUND: A meta-analysis was applied to evaluate the associations between the glutathione-S-transferases (GSTs) M1/T1 gene polymorphisms and male infertility in Chinese populations. METHODS: A comprehensive search for articles was conducted from PubMed, Web of Science, Embase, China biology medical literature database (CBM), China National Knowledge Infrastructure (CNKI), VIP, and Chinese literature database(Wang fang) up to April 30, 2018. All of the statistical analyses were performed using Review Manager 5.3 and Stata 14.0. RESULTS: Ten studies on GSTM1 gene polymorphism involving 3302 cases and 1959 controls, and ten studies on GSTT1 gene polymorphism involving 3048 cases and 1861 controls were included in this meta-analysis. Overall, the null genotype of GSTM1/GSTT1 was significantly related to male infertility risk in Chinese populations (GSTM1, OR = 1.35, 95% CI: 1.02-1.78; GSTT1, OR = 1.40, 95% CI: 1.15-1.70). In subgroup analyses stratified by infertility type, significant association was observed between GSTT1 null genotype and male infertility in both nonobstructive azoospermia (NOA) and oligoasthenozoospermia (OAT). However, the GSTM1 null genotype was associated with OAT, but not NOA in Chinese populations. The sensitivity analysis confirmed the reliability and stability of the meta-analysis. CONCLUSION: Our meta-analysis supports that the GSTM1/GSTT1 null genotype might contribute to individual susceptibility to male infertility in Chinese populations.

Reliability and validity of a new accelerometer-based device for detecting physical activities and energy expenditure.

BACKGROUND: Objective assessments of sedentary behavior and physical activity (PA) by using accelerometer-based wearable devices are ever expanding, given their importance in the global context of health maintenance. This study aimed to determine the reliability and validity of a new accelerometer-based analyzer (Fibion) for detecting different PAs and estimating energy expenditure (EE) during a simulated free-living day. METHODS: The study consisted of two parts: a reliability (n = 18) and a validity (n = 19) test. Reliability was assessed by a 45 min protocol of repeated sitting, standing, and walking (i.e., 3 × 15 min, repeated twice), using both Fibion and ActiGraph. Validity was assessed by a 12 h continuous sequence tasks of different types (sitting, standing, walking, and cycling) and intensities (light [LPA], moderate [MPA], and vigorous [VPA]) of PA. Two Fibion devices were worn on the thigh (FT) and in the pocket (FP), respectively and were compared with criteria measures, such as direct observation (criterion 1) and oxygen consumption by a portable gas analyzer, K4b2 (criterion 2). RESULTS: FT (intra-class correlation coefficients (ICCs): 0.687-0.806) provided similar reliability as the Actigraph (ICCs: 0.661-0.806) for EE estimation. However, the measurement error (ME) of FT compared to the actual time records indicated an underestimation of duration by 5.1 ± 1.2%, 3.8 ± 0.3% and 14.9 ± 2.6% during sitting, walking, and standing, respectively. During the validity test, FT but not FP showed a moderate agreement but lager variance with the criteria (1 and 2) in assessing duration of sitting, long sitting, LPA, MPA, and VPA (p > 0.05, ICCs: 0.071-0.537), as well as for EE estimation of standing, LPA, MPA, and VPA (p > 0.05, ICCs: 0.673-0.894). CONCLUSIONS: FT provided similar reliability to that of the Actigraph. However, low correlations between subsequent measurements of both devices indicated large random MEs, which were somewhat diminished during the simulated 12 h real-life test. Furthermore, FT may accurately determine the types, intensities of PA and EE during prolonged periods with substantial changes in postures, indicating that the location of the accelerometer is essential. Further study with a large cohort is needed to confirm the usability of Fibion, especially for detecting the low-intensity PAs.

Common variants in ZMIZ1 and near NGF confer risk for primary dysmenorrhoea.

Primary dysmenorrhoea, defined as painful menstrual cramps in the absence of pelvic pathology, is a common problem in women of reproductive age. Its aetiology and pathophysiology remain largely unknown. Here we performed a two-stage genome-wide association study and subsequent replication study to identify genetic factors associated with primary dysmenorrhoea in a total of 6,770 Chinese individuals. Our analysis provided evidence of a significant (P<5 × 10-8) association at rs76518691 in the gene ZMIZ1 and at rs7523831 near NGF. ZMIZ1 has previously been associated with several autoimmune diseases, and NGF plays a key role in the generation of pain and hyperalgesia and has been associated with migraine. These findings provide future directions for research on susceptibility mechanisms for primary dysmenorrhoea. Furthermore, our genetic architecture analysis provides molecular support for the heritability and polygenic nature of this condition.

Inhaled insulin provides improved glycemic control in patients with type 2 diabetes mellitus inadequately controlled with oral agents: a randomized controlled trial.

BACKGROUND: The long-term benefits of good glycemic control are well established. The aim of this proof-of-concept study was to determine whether glycemic control can be improved in patients with type 2 diabetes mellitus with suboptimal glycemic control, despite therapeutic dosages of oral antihyperglycemic agents (OHAs), by the addition of preprandial inhaled insulin (INH). METHODS: Sixty-eight patients with inadequately controlled type 2 diabetes mellitus (glycosylated hemoglobin, 8.1%-11.9%), despite therapy with a sulfonylurea and/or metformin, were randomized to receive INH in addition to their prestudy OHA therapy (INH + OHA group, n = 32) or to continue taking their prestudy OHA alone for 12 weeks (OHA group, n = 36). Premeal INH doses were delivered in 1 to 2 inhalations of 1-mg or 3-mg doses (equivalent to 3 IU and 9 IU, respectively, of subcutaneously injected regular insulin). RESULTS: At week 12, there was a significantly greater reduction in glycosylated hemoglobin for the INH + OHA cohort (mean reduction, -2.3%) compared with the OHA-only cohort (mean reduction, -0.1%, P<.001). Eleven patients (34%) receiving INH + OHA achieved glycosylated hemoglobin values of less than 7%, compared with none taking OHAs only. Fasting plasma glucose improved significantly more in the INH + OHA group compared with the OHA-only group (-60.69 mg/dL (-3.37 mmol/L] greater reduction, P<.001), and the postprandial increase in glucose was significantly lower in those patients receiving INH + OHA (P =.02). There was 1 report of severe hypoglycemia in the INH + OHA group (home blood glucose, 54 mg/dL [3.0 mmol/L]) and a greater increase in body weight. Pulmonary function was unchanged in both groups. CONCLUSION: The addition of preprandial INH to existing OHAs improves glycemic control without the need for injections in patients with type 2 diabetes mellitus failing to achieve satisfactory control with OHAs alone.