Synthesis of Multisubstituted 1,2,3-Triazoles: Regioselective Formation and Reaction Mechanism.

A synthetically useful approach to functionalized triazoles is described via the reaction of ß-carbonyl phosphonates and azides. 1,4- and 1,5-disubstituted and 1,4,5-trisubstituted triazoles can be regio- and chemoselectively accessed under mild conditions in good to excellent yields (31 examples, up to 99%). A mechanism is proposed that rationalizes the avoidance of the 4-phosphonate byproducts, which is aligned with crystallographic and experimental evidence.

Effect of nalbuphine plus ropivacaine on vaginal labor in epidural analgesia.

BACKGROUND: Various approaches using epidural analgesia have been employed for relieving labor pain and promoting spontaneous delivery. We aimed to evaluate the effect of nalbuphine and ropivacaine versus fentanyl and ropivacaine on the duration of delivery in parturients. METHODS: Clinical data of 160 full-term primiparous women who received either nalbuphine or fentanyl in combination with ropivacaine infusion for epidural labor analgesia in our hospital from December 2020 to May 2022 were retrospectively analyzed. The participants were divided into two groups based on anesthesia methods: nalbuphine group (NR group, n = 78) received 0.2 mg/mL nalbuphine combined with 0.1% ropivacaine hydrochloride for patient-controlled epidural analgesia (PCEA) and fentanyl group (FR group, n = 82) received 2 ug/mL fentanyl citrate and 0.1% ropivacaine hydrochloride for PCEA. Both groups received an epidural blockade for labor analgesia at lumbar 2-3 interspace. The duration of the first, second, and third stages of labor, the onset of analgesia, and time before delivery (T0), 15 min of analgesia (T1), 30 min of analgesia (T2), full opening of the uterine opening (T3),exerts force during childbirth(T4), heart rate (HR), blood pressure (BP), blood saturation (SpO2), visual analogue pain scale (VAS) score, Ramsay sedation score, and modified Bromage score, and 5 min were recorded at 2 h postpartum (T5). The neonatal Apgar score, neonatal behavioral neurological assessment (NBNA) score, maternal nausea, vomiting, and itchy skin were recorded. RESULTS: Compared with the FR group, the first stage of labor duration (p < 0.05) and total duration of labor (p < 0.05) were shortened and the onset of analgesia (p < 0.05) was increased in the NR group. NR group had lower incidence of urinary retention than FR group (p < 0.05). The maternal and neonatal investigational parameters and scores had no significant difference between the two groups. CONCLUSIONS: Nalbuphine combined with ropivacaine in epidural block labor has a faster onset of analgesia and has a lower incidence of urinary retention than fentanyl combined with ropivacaine, and nalbuphine shortens the duration of the first and total stages of labor. Both nalbuphine and fentanyl can reduce pain during labor, have little effect on maternal hemodynamics, and have no significant effect on neonatal Apgar or NBNA scores.

Role of contrast-enhanced ultrasonography in MR-guided focused ultrasound ablation on uterus fibroids: lesion selection and assessment of ablative effects.

OBJECTIVES: To determine whether contrast-enhanced ultrasonography (CEUS) can be used for selecting lesions and assessing the ablative effects of MRgFUS ablation on uterus fibroids, compared with MR imaging. METHODS: This retrospective study was approved by the institutional review board of our hospital. From April 2018 to November 2019, a total of 44 symptomatic fibroids in 38 patients who underwent MRgFUS ablation were included. The association between pre-ablation characteristics on CEUS/MR imaging and the non-perfusion volume (NPV) after ablation was analyzed using multivariable linear regression analysis. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve values was compared between the CEUS and MR imaging regression models. NPV after ablation was compared between CEUS and enhanced MR imaging. RESULTS: On CEUS, entangled branch vessels, fast-in, and fast-out patterns were significantly associated with NPV, with an AUC of 0.95 (95% CI; 0.88, 1.00). On MR imaging, hyper-intensity on T2-weighted images (T2WI), hyper-intense ring-like signal on T2WI images, and hyper-enhancement on contrast-enhanced T1WI images were correlated with NPV, with an AUC of 0.86 (95% CI; 0.70, 1.00). After ablation, no differences in NPV were noted between contrast-enhanced T1WI (84.13 ± 75.42 cm3) and CEUS (80.22 ± 76.49 cm3). CONCLUSIONS: Some pre-ablation characteristics of uterine fibroids on CEUS were associated with NPV after MRgFUS. CEUS may contribute to the evaluation of ablative outcomes and patient selection, similar to MR imaging. KEY POINTS: • Contrast-enhanced ultrasonography (CEUS) is effective for selecting the appropriate uterine fibroids before MR-guided focused ultrasound (MRgFUS) ablation and evaluating non-perfusion volumes (NPV) after ablation, as a potential alternative to MR imaging. • Before ablation, entangled branch vessels, fast-in, and fast-out patterns on CEUS were significantly associated with NPV after MRgFUS. • No significant differences in NPV were detected between contrast-enhanced T1WI and CEUS after ablation.

Gender- and age-related differences in distinct phenotypes of hypertrophic cardiomyopathy-associated mutation MYBPC3-E334K.

The mutation MYBPC3-E334K is a culprit mutation of hypertrophic cardiomyopathy (HCM). The pathogenicity of MYBPC3-E334K is conflicting in ClinVar because of the limited segregation data and the relatively high frequency in gnomAD (0.03% overall, with 0.3% in East Asians and 0.8% in Japanese). The main aim is to clarify the clinical importance and phenotype-genotype correlations in subjects with or without MYBPC3-E334K alone. The prevalence of MYBPC3-E334K was sequenced in 1017 HCM unrelated probands. The clinical features, morphology phenotypes, and electrical phenotypes were further analyzed according to the phenotype and genotype status in families with single-mutation MYBPC3-E334K. Nine of 1017 (0.88%) unrelated HCM probands were detected harboring MYBPC3-E334K, and three of them harbored a second variant in sarcomere protein gene. Family study and co-segregation analyses indicated that patients with single-mutation MYBPC3-E334K showed autosomal dominant mode of inheritance with incomplete penetrance. The overall disease penetrance was 52.6%, and the disease penetrance was higher in males than in females (100% in men vs 25% in women, p = 0.003). The mean age at diagnosis of males was approximately 25 years younger than females (36.57 ± 18.65 vs 62.33 ± 12.10, p = 0.062). The variant MYBPC3-E334K was classified as a likely pathogenic variant, and a second sarcomere variant did not reveal obvious cumulative effects. The patients harboring single-mutation MYBPC3-E334K had incomplete penetrance, and males demonstrated higher penetrance and early onset HCM than females. A second sarcomere variant did not reveal obvious cumulative effects.

Preoperative evaluation and prediction of clinical scores for hepatocellular carcinoma microvascular invasion: a single-center retrospective analysis.

INTRODUCTION: Microvascular invasion (MVI) of is generally considered to be an important prognostic factor for hepatocellular carcinoma (HCC) after operation, An accurate prediction of MVI before operation is helpful for clinical decision-making before operation. MATERIAL AND METHODS: A retrospective analysis of 227 cases of hepatocellular carcinoma patients after hepatectomy has been confirmed the pathological result whether there was MVI, and has been determined the independent risk factors of MVI. Based on these independent risk factors, we constructed a clinical scoring risk model for predicting MVI. RESULTS: Among the 227 patients with HCC, 74 (34.6%) were MVI positive. Using receiver operating characteristic (ROC) curve and logistic regression model, we found that alpha-fetoprotein(AFP)≥158 ng/mL(odds ratio[OR] = 4.152,95% confidence interval [95%CI]:1.602∼10.760,p = 0.003), Des-γ-carboxy prothrombin (DCP)≥178mAU/mL(OR = 9.730,95%CI:3.392∼27.910,p < 0.001), circulating tumor cells (CTCs)≥3/3.2 ml(OR = 7.747,95%CI:3.019∼19.881,P < 0.001), maximum tumor diameter≥59 mm(OR = 3.467,95%CI:1.368∼8.669,p = 0.008) and tumor margin unsmoothness(OR = 0.235,95%CI:0.096∼0.573,p = 0.001) were independent risk factors for MVI, they predicted that the area under the curve of MVI was 0.752, 0.777, 0.857, 0.743 and 0.333, respectively. Based on these five independent risk factors, we constructed a clinical scoring risk model for predicting MVI. The model predicts that the area under the curve of MVI is 0.922, and its prevalence rate from 0 to 5 are 3.1%(1/32), 5.3%(4/76), 12.2%(5/41), 66.7%(20/30), 87.9%(29/33), 100%(15/15), respectively (P < 0.001). CONCLUSION: Based on AFP, DCP, CTC, maximum tumor diameter and tumor margin unsmoothness, we constructed a model to predict the risk of MVI clinical score, so as to make a more accurate individualized treatment plan before operation, which has important clinical significance and application prospect to improve the curative effect of HCC.

Characterization of a Putative S-layer Protein of a Colonial Microcystis Strain.

Cell surface structure plays a key role in Microcystis colony formation. The S-layer is a crystalline array of monomolecular proteins that constitute the outermost component of the cyanobacterial cell envelope. To date, no biochemical characterization of the S-layer protein in Microcystis has been reported. Here, we compared S-layer on the cell wall of the unicellular strain Microcystis aeruginosa PCC7806 with the colonial strain M. aeruginosa XW01. We observed crystalline S-layers in XW01 cell walls; however, similar structures were not observed in PCC7806. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis revealed a thick putative S-layer protein band with an apparent molecular weight of 70 kDa extracted from XW01 cells, as well as an S-layer peptide fragment with the sequence ETYPLLAAPGAATDATR, similar to the translated product from PCC7806 unknown gene CAO89090.1. The amino acid composition of the translated CAO89090.1 product shared biochemical characteristics with those of bacterial S-layer proteins. Furthermore, a 1002-bp DNA fragment amplified from XW01 displayed 95% similarity with the CAO89090.1 gene, while the S-layer gene expression in XW01 was 36-fold higher than that observed in PCC7806. These data suggested that the S-layer protein plays a key role in Microcystis colony formation due to its significant contribution to cell surface hydrophobicity.

Investigation of myocardial dysfunction using three-dimensional speckle tracking echocardiography in a genetic positive hypertrophic cardiomyopathy Chinese family.

BACKGROUND: We previously reported four heterozygous missense mutations of MYH7, KCNQ1, MYLK2, and TMEM70 in a single three-generation Chinese family with dual Long QT and hypertrophic cardiomyopathy phenotypes for the first time. However, the clinical course among the family members was various, and the potential myocardial dysfunction has not been investigated. OBJECTIVES: The objective of this study was to investigate the echocardiographic and electrocardiographic characteristics in a genetic positive Chinese family with hypertrophic cardiomyopathy and further to explore the association between myocardial dysfunction and electric activity, and the identified mutations. METHODS: A comprehensive echocardiogram - standard two-dimensional Doppler echocardiography and three-dimensional speckle tracking echocardiography - and electrocardiogram were obtained for members in this family. RESULTS: As previously reported, four missense mutations - MYH7-H1717Q, KCNQ1-R190W, MYLK2-K324E, and TMEM70-I147T - were identified in this family. The MYH7-H1717Q mutation carriers had significantly increased left ventricular mass indices, elevated E/e' ratio, deteriorated global longitudinal stain, but enhanced global circumferential and radial strain compared with those in non-mutation patients (all p<0.05). The KCNQ1-R190W carriers showed significantly prolonged QTc intervals, and the MYLK2-K324E mutation carriers showed inverted T-waves (both p<0.05). However, the TMEM70-I147T mutation carriers had similar echocardiography and electrocardiographic data as non-mutation patients. CONCLUSIONS: Three of the identified four mutations had potential pathogenic effects in this family: MYH7-H1717Q was associated with increased left ventricular thickness, elevated left ventricular filling pressure, and altered myocardial deformation; KCNQ1-R190W and MYLK2-K324E mutations were correlated with electrocardiographic abnormalities reflected in long QT phenotype and inverted T-waves, respectively.

The Cumulative Effects of the MYH7-V878A and CACNA1C-A1594V Mutations in a Chinese Family with Hypertrophic Cardiomyopathy.

AIMS: We investigated the pathogenesis of MYH7-V878A and CACNA1C-A1594V mutations in a Chinese family with hypertrophic cardiomyopathy. METHODS: Clinical, electrocardiographic (ECG), echocardiographic, and cardiac magnetic resonance (CMR) examinations of members of a Chinese family were followed by exon and boarding intron analyses of 96 genes in the proband using second-generation sequencing. We confirmed the mutations by bidirectional Sanger sequencing in the members and in 300 healthy controls. RESULTS: We detected MYH7-V878A and CACNA1C-A1594V mutations in this family. The members with both mutations showed inverted T-waves and ST-segment depression in ECG recordings, severe left ventricular (LV) hypertrophy in echocardiography, and myocardial fibrosis in CMR; subject II-11 did not show late gadolinium enhancement. Among those with only the MYH7-V878A mutation, subject III-7 showed abnormal ECG recordings, asymmetric septal hypertrophy, and myocardial fibrosis, and subjects II-13 and III-15 showed some abnormal repolarization, borderline LV wall thickness, and normal CMR findings. Those with only the CACNA1C-A1594V mutation showed nearly normal readings in all examinations. The members with both mutations displayed more severe LV hypertrophy and elevated LV filling pressure than those with 1 or no mutation (p < 0.05). CONCLUSION: Our results suggest that the pathogenesis of MYH7-V878A and CACNA1C-A1594V mutations may have a cumulative effect.

An RNA Molecule Derived From Sendai Virus DI Particles Induces Antitumor Immunity and Cancer Cell-selective Apoptosis.

Inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ-E) induces anticancer immunity and cancer cell-selective apoptosis through the recognition of viral RNA genome fragments by retinoic acid-inducible gene-I (RIG-I). Here, we discovered that the "copy-back" type of defective-interfering (DI) particles that exist in the Cantell strain of HVJ induced the human PC3 prostate cancer cell death more effectively than the Sendai/52 strain or Cantell strain, which contain fewer DI particles. DI particle genomic RNA (~550 bases) activated proapoptotic genes such as Noxa and/or TNF-related apoptosis-inducing ligand (TRAIL) in human prostate cancer cells to induce cancer cell-selective apoptosis. DI particle-derived RNA was synthesized by in vitro transcription (in vitro transcribed (IVT)-B2). IVT-B2 RNA, which has a double-stranded region in its secondary structure, promoted a stronger anticancer effect than IVT-HN RNA, which does not have a double-stranded region in its secondary structure. The intratumoral transfection of IVT-B2 significantly reduced the volume of a human prostate tumor and induced tumor cell apoptosis in the xenograft mouse model. Moreover, the involvement of natural killer (NK) cells in IVT-B2-RNA-induced anticancer effects was also suggested. These findings provide a novel nucleic acid medicine for the treatment of cancer.

Hinokitiol induces autophagy in murine breast and colorectal cancer cells.

Hinokitiol is found in the heartwood of cupressaceous plants and possesses several biological activities. Hinokitiol may play an important role in anti-inflammation and antioxidant processes, making it potentially useful in therapies for inflammatory-mediated disease. Previously, the suppression of tumor growth by hinokitiol has been shown to occur through apoptosis. Programmed cell death can also occur through autophagy, but the mechanism of hinokitiol-induced autophagy in tumor cells is poorly defined. We used an autophagy inhibitor (3-methyladenine) to demonstrate that hinokitiol can induce cell death via an autophagic pathway. Further, we suggest that hinokitiol induces autophagy in a dose-dependent manner. Markers of autophagy were increased after tumor cells were treated with hinokitiol. In addition, immunoblotting revealed that the levels of phosphoprotein kinase B (P-AKT), phosphomammalian target of rapamycin (P-mTOR), and phospho-p70 ribosomal s6 kinase (P-p70S6K) in tumor cells were decreased after hinokitiol treatment. In conclusion, our results indicate that hinokitiol induces the autophagic signaling pathway via downregulation of the AKT/mTOR pathway. Therefore, our findings show that hinokitiol may control tumor growth by inducing autophagic signaling.

The impact of intermittent and repetitive cold stress exposure on endoplasmic reticulum stress and instability of atherosclerotic plaques.

BACKGROUND: The incidence of acute coronary syndrome caused by the rupture of atherosclerotic plaque and subsequent arterial thrombosis increases as the weather gets colder. However, the association between cold stress and atherosclerotic plaque rupture is currently unknown. METHODS: An atherosclerotic plaque model was established in rabbits by balloon injury and a high-fat diet with or without cold stress (4 °C, 1 hour per day, 20 weeks) at the onset of modeling. Additionally, oxidized low-density lipoprotein (ox-LDL) was applied to induce the formation of macrophage foam cells in vitro. RESULTS: Serum lipid profiles and inflammatory cytokines (ox-LDL, high-sensitivity C-reactive protein, and interleukin-8) were significantly higher in cold stress-exposed rabbits than in controls (P<0.05). Animals with atherosclerotic lesions that were exposed to cold stress had increased macrophages, foam cells, intima-media thickness, and neovascularization in the plaque, along with significantly thinned plaque fibrous caps. Moreover, we found that cold stress induced more apoptotic cells in the atherosclerotic plaques and up-regulated endoplasmic reticulum stress (ERS)-associated proteins CHOP, GRP78, and p-JNK (P<0.05). In addition, tunicamycin treatment promoted ox-LDL-induced apoptosis, expression of CHOP and GPR78, and the p-JNK level in macrophage foam cells, while JNK inhibitor sp600125 reduced cell apoptosis and the p-JNK level. The three main ERS sensors sensors phosphorylated extracellular signal-regulated kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring enzyme1 (IRE1) declined significantly after ox-LDL treatment. CONCLUSIONS: Cold stress may enhance the instability of atherosclerotic plaques through activating ERS and enhancing cell apoptosis. Up-regulated CHOP levels mediated by PERK and ATF6 and the activated IRE1-XBP1-JNK pathway contributed to the apoptosis of foam cells.

A study on the relationship between gut microbiota and intrahepatic cholestasis of pregnancy.

Objective: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with a high incidence of complications in the mid and late stages of gestation. This study investigates differences in the composition of intestinal flora among pregnant women diagnosed with ICP, employing Illumina MiSeq high-throughput sequencing technology. Methods: This case-control study obtained patient data from the hospital information system (HIS) and the laboratory information system (LIS). Fecal samples were collected from 25 pregnant women who did not undergo intestinal preparation before delivery between December 2020 and March 2021. Whole-genome analysis was performed. PCR was used to amplify the 16S rRNA V3-V4 variable region, which was then sequenced. Alpha and beta diversity were computed, and the maternal intestinal flora's abundance and composition characteristics were analyzed. Differences in intestinal flora between the two sample groups were examined. Results: Bacteroides and Proteobacteria exhibited positive correlations with TBIL and IBIL. Betaproteobacteria, Gammaproteobacteria, and Erysipeiotrichi showed positive correlations with TBIL, IBIL, and DBIL, while Lactobacillus, Delftia, and Odoribacter demonstrated positive correlations with ALT. Conclusion: The ICP group displayed significantly higher levels of total bile acid and ALT compared to the control group. The intestinal flora composition comprised four primary phyla: Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria. ICP patients exhibited a lower relative abundance of intestinal flora across different levels of community composition when compared to the control group. Specific correlations between certain intestinal flora and clinical liver parameters were identified.

Genotype diversity of methicillin-resistant Staphylococcus aureus in Shenyang, China.

BACKGROUND: The aim of this study was to better understand methicillin-resistant Staphylococcus aureus (MRSA) at the molecular level by investigating the genotypic characteristics and evolutionary patterns of MRSA clones in Shenyang, China. METHODS: We analyzed the molecular epidemiology of 60 MRSA isolates in Shenyang, China, between 2002 and 2008, using pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing, and S. aureus protein A (spa) typing. They were examined for their antimicrobial susceptibilities. RESULTS: Among the 60 isolates, ST239 was identified most frequently (34 isolates; 58%), followed by ST5 (20 isolates; 34%). Nine spa types were obtained and 4 PFGE strain families (A, B, C, and D) were resolved. Spa type t030, which corresponded to PFGE genotypes A1, A3, and A4, constituted 45% (27/60) of all isolates; spa type t037, which corresponded to PFGE type A2, accounted for 13% (8/60) of all isolates. These 2 spa genotypes belonged to ST239 and carried SCCmec type III. Isolates genotyped as spa type t002 comprised 27% (16/60) of the study set and included isolates typed as PFGE B1 and B2, ST5, and SCCmec II. Most of MRSA isolates belonging to ST239 were susceptible to trimethoprim-sulfamethoxazole. The minimum inhibitory concentration (MIC50) of vancomycin among MRSA isolates belonging to ST5 (2 mg/l) was higher than that for other isolates (1 mg/l). CONCLUSIONS: These data document 2 major epidemic MRSA clones in Shenyang, China: ST239-MRSA-SCCmec type III-t037/t030 and ST5-MRSA-SCCmec type II-t002.

The Soft Prefabricated Orthopedic Insole Decreases Plantar Pressure during Uphill Walking with Heavy Load Carriage.

This study aimed to investigate the effect of varying the hardness of prefabricated orthopedic insoles on plantar pressure and muscle fatigue during uphill walking with a heavy backpack. Fifteen healthy male recreational athletes (age: 20.4 ± 1.0 years, height: 176.9 ± 5.7 cm, weight: 76.5 ± 9.0 kg) wore prefabricated orthopedic insoles with foot arch support; a heel cup with medium (MI), hard (HI), and soft (SI) relative hardnesses; and flat insoles (FI). They performed treadmill walking on uphill gradients with 25 kg backpacks. The plantar pressure and surface electromyographic activity were recorded separately, in 30 s and 6 min uphill treadmill walking trials, respectively. The HI, MI, and SI significantly decreased peak plantar pressure in the lateral heel compared to FI. The MI and SI significantly decreased the peak plantar pressure in the fifth metatarsal compared to FI. The MI significantly reduced the pressure-time integral in the lateral heel compared to FI. The HI significantly increased the peak plantar pressure and pressure-time integral in the toes compared to other insoles, and decreased the contact area in the metatarsal compared to SI. In conclusion, a prefabricated orthopedic insole made of soft material at the fore- and rearfoot, with midfoot arch support and a heel cup, may augment the advantages of plantar pressure distribution during uphill weighted walking.

[Content, Distribution, Source Analysis, and Risk Assessment of PAHs in Arable Soils of Taiyuan].

PAHs (polycyclic aromatic hydrocarbons) accumulated in arable soils have significant impacts on farmland quality and human health, which has attracted wide attention from scientists and the public. A total of 22 arable soil samples were collected from Taiyuan, an old industrial city, including three districts (industrial zones, hilly areas, and sewage irrigation area), and the contents of 21 PAHs were detected using the GC-MS method. The sources of PAHs in soils were analyzed using the diagnostic ratios (DRs) method and positive matrix factorization (PMF) model, and the soil health risks were analyzed using the incremental lifetime cancer risk (ILCR) model. The results indicated that the average concentrations of Σ21PAHs and Σ16PAHs in arable soils of Taiyuan were 934.6 ng·g-1 and 787.7 ng·g-1, respectively, which were lower than the soil pollution risk screening value of agricultural land stipulated in GB 15168-2018. 3-5 rings PAHs were the dominant components, accounting for~90% of the Σ21PAHs. Approximately 60% of sites in industrial zones, 13% in hilly areas, and 33% in the sewage irrigation area had high PAHs contents larger than 1000 ng·g-1. The spatial distribution of PAHs showed that more severe PAHs pollution in the soil occurred in industrial areas than that in the other two districts. The DRs suggested that the combustion of coals, bio-masses, and traffic emissions were the dominant sources for PAHs pollution in arable soils in Taiyuan. The simulation results of the PMF model indicated that the sources and contribution rates of PAHs in cultivated soils were coal and biomass burning sources (59%), traffic sources (22%), and coking sources (19%). The risk assessment confirmed that the arable soils in Taiyuan had high potential carcinogenic risks; thus, more attention should be paid to the PAHs pollutions in arable soils.

Using Simulation Optimization to Solve Patient Appointment Scheduling and Examination Room Assignment Problems for Patients Undergoing Ultrasound Examination.

This study investigates patient appointment scheduling and examination room assignment problems involving patients who undergo ultrasound examination with considerations of multiple examination rooms, multiple types of patients, multiple body parts to be examined, and special restrictions. Following are the recommended time intervals based on the findings of three scenarios in this study: In Scenario 1, the time interval recommended for patients' arrival at the radiology department on the day of the examination is 18 min. In Scenario 2, it is best to assign patients to examination rooms based on weighted cumulative examination points. In Scenario 3, we recommend that three outpatients come to the radiology department every 18 min to undergo ultrasound examinations; the number of inpatients and emergency patients arriving for ultrasound examination is consistent with the original time interval distribution. Simulation optimization may provide solutions to the problems of appointment scheduling and examination room assignment problems to balance the workload of radiological technologists, maintain high equipment utilization rates, and reduce waiting times for patients undergoing ultrasound examination.

Inhibition of Nodal suppresses angiogenesis and growth of human gliomas.

Angiogenesis is the hallmark of malignant gliomas positively correlated with the vascular endothelial growth factor (VEGF) expression. We previously reported that expression levels of Nodal, a member of transforming growth factor-ß super family, correlate with the malignant invasive behavior of human glioma cells. In this study, we show that knockdown of Nodal suppresses glioma angiogenesis by inhibition of VEGF. In human primary glioma specimens, expression of Nodal positively correlates with WHO glioma tumor grades and expression of VEGF in the corresponding glioma specimens. In human U87MG glioma cells, knockdown of endogenous Nodal by RNA interference (RNAi) significantly decreases colony formation and secretion of VEGF. In vivo, cellular depletion of Nodal in U87MG inhibited brain glioma growth and prolonged the survival of mice with U87MG/shNodal glioma compared with controls. Inhibition of Nodal suppressed tumor vessel growth in U87MG gliomas. Using Nodal inhibitor (SB431542), silencing Nodal, or overexpressing Nodal in the U87MG, GBM8401, and GBM glioma cells, our further experiments revealed that Nodal-induced VEGF expression might, at least in part, mediate through the ERK1/2-HIF-1α-mediated signaling pathway. Taken together, our data revealed that alteration of Nodal expression in glioma cells resulted in changes to VEGF secretion, and subsequent colony formation, in vivo tumor growth, and angiogenesis, all of which are consistent with the regulation of VEGF through the ERK1/2-HIF-1α-mediated signaling, suggesting that Nodal may serve as a potential therapeutic target for the treatment of human gliomas.

Contributions of Ergonomics, Psychological Factors, and Sleep Disturbances to Lower Back Pain Among Taiwanese Workers.

OBJECTIVE: We investigated the contributions of ergonomics, psychological factors, and sleep disturbances to lower back pain (LBP). METHODS: A nationwide survey of sampled 27,508 (2.6‰) Taiwanese workers was conducted in 2010. Definition of outcome was LBP affecting work performance in the past year. Predictor variables included age, body mass index, ergonomic factors, job control, psychological demands, and sleep disturbances. Mutually adjusted relative risks were examined using general linear models, followed by aPAR. RESULTS: 18,353 workers were included in the multivariate regression model. The three first significant risk factors to LBP included heavy lifting or awkward posture, sleep disturbances, and high psychological demands (aPAR = 13.5%, 8.7%, 5.7% respectively in men and 6.1%, 11.8%, 5.9% in women). CONCLUSIONS: In addition to ergonomic exposure, sleep disturbances and high psychological demands significantly contributed to LBP.

Body volume estimation equation for male laborers in Taiwan.

The purpose of this study was to develop a body volume (BV) estimation equation for male laborers in Taiwan with body weight (W) and stature height (H) as initial estimators. A three-dimensional (3D) body scanner and a 3D foot scanner were used to measure the 3D range data of 100 male laborers in this study. Subjects' BV was extracted from the 3D body model, and H and W were used as independent variables in regression analysis. The results show that the final BV estimation equation is BV = 1122.927 × W0.972, with R2 = 0.949. Thirty extra male subjects were scanned to compare this BV estimation equation with those in previous studies. The results show that this BV estimation equation had the smallest absolute mean difference at 1.1458 L and the smallest standard error of the estimate at 2.48% in comparison.