Reduced prescription of TNF-inhibitors in chronic arthritis based on therapeutic drug monitoring: A randomized controlled trial.

OBJECTIVE: Dosing of tumour necrosis factor-α inhibitors (TNFis) is not personalized causing interindividual variation in serum drug levels; however, dose optimization is not widely implemented. We hypothesized that some patients are overdosed; thus, drug prescription could be reduced by therapeutic drug monitoring (TDM). METHOD: Independent of disease activity, 239 adults treated for rheumatoid arthritis (n = 99), psoriatic arthritis 15 (n = 48), or spondyloarthritis (n = 92) were recruited for a 48-week prospective, randomized open-label trial. Standard care alone or plus TDM was applied in chronic arthritis patients treated with infliximab (IFX), (n = 81), etanercept (ETN) (n = 79), or adalimumab (ADA) (n = 79). Serum TNFi trough levels assessed at inclusion and every 4 months determined patients within/outside predefined therapeutic intervals, supporting change in prescription or drug switch. The primary endpoint was reduced drug prescription. RESULTS: Compared to standard care, TDM reduced prescribed IFX [-12% (95% confidence interval -20, -3); p = 0.001] and ETN (-15% (-29, 1); p = 0.01], and prolonged the interdosing intervals of ETN [+235% (38, 432); p = 0.02] and ADA [+28% (6, 51); p = 0.04]. Time to drug switch was accelerated (χ2 = 6.03, p = 0.01). No group differences in adverse events, disease activity, or self-reported outcomes were shown, indicating equally sustained remission. CONCLUSIONS: TDM reduced prescription of IFX, ETN, and ADA and identified patients benefiting from accelerated drug switch, thereby minimizing treatment failure, risk of toxicity, and unnecessary adverse events.

Wavelength optimization for the laser treatment of port wine stains.

Based on the well-known principle of selective photothermolysis, laser has been a promising way for the treatment of port wine stains (PWSs). The laser wavelengths used for PWS's clinical treatment include but are not limited to pulsed dye laser (PDL) in 585-600 nm, long-pulse 755-nm alexandrite, and 1064-nm Nd:YAG lasers. The objective of this study was to investigate the optimal wavelength for PWS's laser treatment. A two-scale mathematic model was constructed to simultaneously quantify macroscale laser energy attenuation in two-layered bulk skin and microscale local energy absorption on target blood vessels within Krogh unit. The effects of morphological parameters, including epidermal melanin content, epidermal thickness, dermal blood content, blood vessel depth, and diameter on laser energy deposition within target blood vessels, were investigated from the visible to near-infrared bands (500-1100 nm). The energy deposition ratio of target blood vessel to epidermal surface was proposed to determine the optimal laser wavelength for PWS with different skin morphological parameters. The bioheat transfer modeling and animal experiment are also conducted to prove our wavelength optimization. The optimal wavelengths for lightly pigmented skin with small and shallow target blood vessels are 580-610 nm in the visible band. This wavelength coincides with commercially used PDL. The optimal wavelength shifts to 940 nm as the epidermal pigmentation increases or the size and blood vessel depth increases. The optimal wavelength changes to 1005 nm as the epidermal pigmentation or the size and burying depth of target blood vessel further increases. Nine hundred forty nanometers can be selected as a general wavelength in PWS treatment to meet the need in most widely morphological structure. Lasers with wavelengths in the 580-610, 940, and 1005 nm regions are effective for treating PWS because of their high optical selectivity in blood over the epidermis.

[Application of indocyanine green fluorescence visualization in surgical resection of abdominal wall endometriosis].

Objective: To investigate the feasibility, effectiveness and safety of indocyanine green (ICG) navigation in the surgical resection of abdominal wall endometriosis (AWE). Methods: Seven women undergoing surgery for AWE in First Affiliated Hospital of Sun Yat-sen University (from July 1, 2021 to October 1, 2021) were collected. After exposure of the focus, ICG were used intravenously (0.25 mg/kg) as fluorescent dye for the intraoperative evaluation of AWE vascularization. Resection of the AWE was guided by direct visualization of the focus under standard laparoscopy with a near-infrared (NIR) camera head. Surgical margin around the AWE (3, 6, 9 and 12 point) and the margin under the focus were obtained for postoperative pathological examination of endometriosis. Time from injection to fluorescence visualization, the proportion of fluorescence visualization, time of fully resection of AWE, side effects related to the use of ICG, perioperative complications as well as the pathological result of the surgical margins were recorded. Results: ICG fluorescence of the AWE were seen in 5 patients (5/7). The mean time from injection to fluorescence visualization was (46.7±9.8) s. The mean time of fully resection of AWE was (16.4±7.0) minutes. There were no side effects related to the use of ICG. The rate of class-A wound healing was 7/7. All of the surgical margins were confirmed endometriosis-negative by postoperative pathological examination. Conclusion: ICG fluorescence visualization could conduct accurate resection of AWE, which is clinically safe and effective.

Theoretical Tools to Analyze Anorectal Mechanophysiological Data Generated by the Fecobionics Device.

A mechanical approach is needed for understanding anorectal function and defecation. Fecal continence is achieved by several interacting mechanisms including anatomical factors, anorectal sensation, rectal compliance, stool consistency, anal muscle strength, motility, and psychological factors. The balance is easily disturbed, resulting in symptoms such as fecal incontinence and constipation. Novel technologies have been developed in recent years for studying anorectal function. Especially, the Fecobionics device, a simulated feces, has gained attention recently. This facilitates new analysis of anorectal mechanical function. In this study, a theoretical model is developed to analyze anorectal mechanophysiological data generated by the Fecobionics device. Theoretical approaches can enhance future interdisciplinary research for unraveling defecatory function, sensory-motor disorders, and symptoms. This is a step in the direction of personalized treatment for gastrointestinal disorders based on optimized subtyping of anorectal disorders.

Shock-Induced Damage and Dynamic Fracture in Cylindrical Bodies Submerged in Liquid.

Understanding the response of solid materials to shock loading is important for mitigating shock-induced damages and failures, as well as advancing the beneficial use of shock waves for material modifications. In this paper, we consider a representative brittle material, BegoStone, in the form of cylindrical bodies and submerged in water. We present a computational study on the causal relationship between the prescribed shock load and the resulting elastic waves and damage in the solid material. A recently developed three-dimensional computational framework, FIVER, is employed, which couples a finite volume compressible fluid solver with a finite element structural dynamics solver through the construction and solution of local, one-dimensional fluid-solid Riemann problems. The material damage and fracture are modeled and simulated using a continuum damage mechanics model and an element erosion method. The computational model is validated in the context of shock wave lithotripsy and the results are compared with experimental data. We first show that after calibrating the growth rate of microscopic damage and the threshold for macroscopic fracture, the computational framework is capable of capturing the location and shape of the shock-induced fracture observed in a laboratory experiment. Next, we introduce a new phenomenological model of shock waveform, and present a numerical parametric study on the effects of a single shock load, in which the shock waveform, magnitude, and the size of the target material are varied. In particular, we vary the waveform gradually from one that features non-monotonic decay with a tensile phase to one that exhibits monotonic decay without a tensile phase. The result suggests that when the length of the shock pulse is comparable to that of the target material, the former waveform may induce much more significant damage than the latter one, even if the two share the same magnitude, duration, and acoustic energy.

[Impact of cessation of antiviral therapy at delivery on postpartum liver function in mothers with chronic hepatitis B virus infection].

Objective: To investigate the impact of immediate cessation of antiviral therapy on postpartum liver function and the factors influencing postpartum abnormality in mothers with chronic hepatitis B virus infection. Methods: A retrospective cohort study was conducted. One hundred eighty-eight pregnant women with HBV DNA level > 2×106 IU/ml were enrolled from June 2014 to June 2018. Demographic information and clinical data of liver function and HBV DNA load during gravidity, intrapartum and postpartum period were collected. According to the antiviral treatment recommendations during pregnancy, the women were divided into three groups, namely, tenofovir (TDF), telbivudine (LdT) and control group. Liver function abnormalities among the three groups were compared within 6 months after delivery, and the factors influencing abnormal liver function were analyzed by unconditional logistic regression. Results: Of the 188 cases, 72 cases were in the TDF group, 80 cases in the LdT group, and 36 cases in the control group. Pregnant women in the TDF and LdT groups received oral TDF (300 mg/d) and LdT (600 mg/d) from 28 ± 4 weeks of gestation till delivery. Among the 188 patients, 30 (16.0%) had abnormal postpartum liver function abnormality. The incidence of postpartum liver function abnormality [alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN)] in the TDF, LdT, and control groups was 19.4%, 12.5%, and 16.7%, respectively. The postpartum peak levels of ALT (median, range) in the three groups were 34.5 (12.0-946.0) U/L, 37.5 (12.0-733.8) U/L, and 39.0 (7.0-513.0) U/L, respectively. There was no significant difference between the two indexes among the three groups (P > 0.05). There was no statistically significant difference in the degree of postpartum liver function abnormalities between the three groups (P = 0.944). Most of the liver function abnormalities were mild to moderate (2 × ULN≤ALT < 10 × ULN), and usually resolved spontaneously or by treatment. Univariate and multivariate analysis showed that baseline ALT level during pregnancy was an independent factor associated with postpartum liver function abnormality (OR = 1.031, CI 95%: 1.005-1.058; χ(2) = 5.340, P = 0.021), whereas age, antiviral therapy, HBeAg-positivity, baseline HBV DNA levels, gravidity, parity, preterm delivery and delivery mode were not significantly associated with postpartum liver function abnormality. Conclusion: Cessation of antiviral therapy after delivery did not significantly increase the risk of postpartum liver function abnormality in pregnant women with chronic HBV infection. The ALT level during pregnancy is a factor influencing postpartum liver function abnormality.

Neurocognitive and behavioral functioning in adolescents with sleep-disordered breathing: a population-based, dual-energy X-ray absorptiometry study.

BACKGROUND/OBJECTIVES: Sleep-disordered breathing (SDB) has been associated with neurocognitive and behavioral problems in young children; however, this association is less studied in adolescents. Evidence suggests that obesity plays a key role in the development of SDB, although its relative association with neurobehavioral functioning remains unclear. We examined whether SDB and obesity are associated with neurocognitive and behavioral problems in adolescents. SUBJECTS/METHODS: A total of 421 adolescents (17.0±2.2y, 53.9% male) from the Penn State Child Cohort, a general population sample, underwent a 9-h polysomnography, clinical history, physical examination, neurocognitive evaluation and Dual-energy X-ray Absorptiometry (DXA) scan, and completed the Child or Adult Behavior Checklist. Obstructive sleep apnea (OSA) was defined as an apnea-hypopnea index (AHI)⩾2, primary snoring (PS) as AHI<2+snoring and no-SDB as AHI<2 without snoring. Body weight measures included body mass index (BMI) percentile, waist circumference (WC) and DXA-measured total adipose tissue (TAT). RESULTS: WC and TAT were significantly associated with impaired vigilance, processing speed, working memory, and control interference and greater internalizing and externalizing behaviors, while BMI percentile was marginally associated. SDB per se (PS, AHI or OSA) was not significantly associated with impaired neurocognitive outcomes or greater behavioral problems. However, TAT was significantly associated with impaired vigilance and greater internalizing and externalizing behaviors and, to a lesser extent, slower processing speed and greater control interference, only in adolescents with OSA. CONCLUSIONS: Central obesity, an etiopathogenic mechanism of OSA, is more strongly associated with neurocognitive and behavioral problems in adolescents than SDB alone. Deficits in low-order (vigilance) and high-order (executive) functions and behavioral problems observed in adolescents with OSA are primarily associated with increased central adiposity, a finding not entirely captured with less precise measures of obesity. These data support that OSA and its associated neurocognitive and behavioral morbidity are related to underlying metabolic dysfunction as early as adolescence.

Association of PON1 gene polymorphisms with polycystic ovarian syndrome risk: a meta-analysis of case-control studies.

PURPOSE: Evidences showed that paraoxonase 1 (PON1) gene polymorphism has an impact on women's susceptibility to polycystic ovarian syndrome (PCOS) by influencing the expression and activity of PON1. However, the effects of three PON1 polymorphisms (- 108 C>T, L55M and Q192R) on the incidence of PCOS have generated inconsistent results. Here, we conducted a meta-analysis to investigate the association between PON1 polymorphisms and PCOS risk. METHODS: All eligible trials were identified via systematic searches of multiple literature databases. Outcome data were synthesized by using crude odds ratio with 95% confidence interval. Heterogeneity was assessed with the I2 test. Publication bias and subgroup analyses were also performed. RESULTS: A total of 2449 cases and 1977 controls from nine studies were selected for analysis. The pooled results showed a significant association between PCOS risk and PON1 - 108 C/T polymorphism in the following genetic models [allelic, 0.72 (0.56-0.92); homozygote, 0.51 (0.32-0.82); heterozygote, 0.44 (0.25-0.78); and dominant 0.47 (0.29-0.77)]. For the PON1 192 Q/R polymorphism, a significant relationship was found in the allelic model [0.62 (0.41-0.93)] and recessive model [0.61 (0.37-0.98)]. PCOS risk was also linked to PON1 L55M polymorphism in the heterozygote model [0.62 (0.39-0.98)] and dominant model [0.63 (0.41-0.96)]. CONCLUSIONS: Our study has shown that PON1 - 108 C/T polymorphism might be associated with increased risk of PCOS under the allelic, homozygote, heterozygote, and dominant models. Additionally, PON1 192 Q/R and L55M polymorphisms were significantly related only in the allelic and recessive model, and in the heterozygote and dominant model, respectively.

[Staged transcranial and transsphenoidal surgery for giant pituitary adenomas: a retrospective study of 21 cases].

Objective: To investigate the effect of the second-stage transcranial and transsphenoidal approach for giant pituitary tumors. Methods: A retrospective review of 21 patients, who had undergone the transcranial surgery and then transsphenoidal surgery for giant pituitary adenomas from 2012 to 2015 in the neurosurgery department of West China Hospital, was performed. Visual findings, endocrine presentation, complications, and tumor types were collected. All data were based on clinical feature, MRI, and follow-up. Results: Among the 21 cases, gross total resection of tumor was achieved in 7 of all patients, subtotal in 11, and partial in 3. No intracranial hemorrhage or death occurred postoperatively. Postoperative infectionoccurred in one patient and cerebrospinal fluid leakage occurred in 3 patients. Four patients recovered after treatment. Conclusion: According to the clinical feature and MRI, it is safe and effective to choose the transcranial surgery and then transsphenoidal surgery for specific giant pituitary adenomas, which can improve treatment effects and reduce postoperative complications.

Sevoflurane activates hippocampal CA3 kainate receptors (Gluk2) to induce hyperactivity during induction and recovery in a mouse model.

BACKGROUND: In addition to general anaesthetic effects, sevoflurane can also induce hyperactive behaviours during induction and recovery, which may contribute to neurotoxicity; however, the mechanism of such effects is unclear. Volatile anaesthetics including isoflurane have been found to activate the kainate (GluK2) receptor. We developed a novel mouse model and further explored the involvement of kainate (GluK2) receptors in sevoflurane-induced hyperactivity. METHODS: Maximal speed, mean speed, total movement distance and resting percentage of C57BL/6 mice were quantitatively measured using behavioural tracking software before and after sevoflurane anaesthesia. Age dependence of this model was also analysed and sevoflurane-induced hyperactivity was evaluated after intracerebral injection of the GluK2 receptor blocker NS-102. Neurones from the hippocampal CA3 region were used to undertake in vitro electrophysiological measurement of kainate currents and miniature excitatory postsynaptic potential (mEPSP). RESULTS: Sevoflurane induced significant hyperactivities in mice under sevoflurane 1% anaesthesia and during the recovery period, characterized as increased movement speed and total distance. The hyperactivity was significantly increased in young mice compared with adults (P<0.01) and pre-injection of NS-102 significantly prevented this sevoflurane-induced hyperactivity. In electrophysiological experiments, sevoflurane significantly increased the frequency of mEPSP at low concentrations and evoked kainate currents at high concentrations. CONCLUSIONS: We developed a behavioural model in mice that enabled characterization of sevoflurane-induced hyperactivity. The kainate (GluK2) receptor antagonist attenuated these sevoflurane-induced hyperactivities in vivo, suggesting that kainate receptors might be the underlying therapeutic targets for sevoflurane-induced hyperactivities in general anaesthesia.

It Is Imperative to Establish a Pellucid Definition of Chimeric RNA and to Clear Up a Lot of Confusion in the Relevant Research.

There have been tens of thousands of RNAs deposited in different databases that contain sequences of two genes and are coined chimeric RNAs, or chimeras. However, "chimeric RNA" has never been lucidly defined, partly because "gene" itself is still ill-defined and because the means of production for many RNAs is unclear. Since the number of putative chimeras is soaring, it is imperative to establish a pellucid definition for it, in order to differentiate chimeras from regular RNAs. Otherwise, not only will chimeric RNA studies be misled but also characterization of fusion genes and unannotated genes will be hindered. We propose that only those RNAs that are formed by joining two RNA transcripts together without a fusion gene as a genomic basis should be regarded as authentic chimeras, whereas those RNAs transcribed as, and cis-spliced from, single transcripts should not be deemed as chimeras. Many RNAs containing sequences of two neighboring genes may be transcribed via a readthrough mechanism, and thus are actually RNAs of unannotated genes or RNA variants of known genes, but not chimeras. In today's chimeric RNA research, there are still several key flaws, technical constraints and understudied tasks, which are also described in this perspective essay.

The relative association of obstructive sleep apnea, obesity and excessive daytime sleepiness with incident depression: a longitudinal, population-based study.

BACKGROUND: It is postulated that obstructive sleep apnea (OSA) is a risk factor for the development of depression. However, obesity and excessive daytime sleepiness (EDS) are associated with both OSA and depression. The goal of this study was to examine the relative contribution of OSA, obesity and EDS to incident depression. METHODS: A representative random sample of 1137 adults without depression from the Penn State Adult Cohort was followed up after 7.5 years. All subjects underwent a full medical examination and polysomnography at baseline. OSA was defined as an apnea/hypopnea index (AHI) ⩾5, overweight as a body mass index (BMI) of 25-29.9 kg m(-)(2), obesity as a BMI⩾30 kg m(-)(2) and EDS as moderate-to-severe drowsiness/sleepiness and/or irresistible sleep attacks. RESULTS: Overweight, obesity and EDS were associated with incident depression, whereas OSA alone was not. Overweight was associated with incident depression in women, while obesity and EDS were associated with incident depression in both genders. The association of overweight and obesity with incident depression was independent of premorbid emotional distress, while that of EDS was not. The association between BMI and EDS with incident depression was stronger in women 20-40 years old. The severity of EDS predicted incident depression in those with OSA, while AHI or oxygen desaturation did not. CONCLUSIONS: Overweight, obesity and EDS are the main predictors of incident depression. Obesity may be linked to depression through psychobiological mechanisms, while EDS may be an early sign of depression. Obesity should be a target of our preventative strategies for depression.

Evaluation of four protein extraction methods for proteomic analysis of mango peel.

The peel of mango (Mangifera indica L.) is a special plant tissue that contains many compounds that interfere with protein extraction. A successful separation with Two-dimensional electrophoresis (2-DE) is the key step for proteomic analysis. To evaluate the efficiencies of mango peel protein extraction for 2-DE, four extraction methods were tested: 1) 2-D clean-up kit, 2) trichloroacetic acid/acetone precipitation, 3) phenol extraction, 4) phenol with methanol/ammonium acetate precipitation. The results showed that the phenol with methanol/ammonium acetate precipitation produced the best quality protein extraction and separation. Proteins were separated in 30-70 and >70 kDa ranges better than with the other methods. Acidic proteins had better resolution with fewer horizontal and vertical streaks. Sixteen proteins were identified by maxtrix-assisted laser desorption/ ionisation time-of-flight tandem mass spectrometry (MALDI-TOF/ TOF-MS/MS). The result demonstrated that each of these four methods can be used to prepare mango peel proteins. The phenol with methanol/ ammonium acetate precipitation was the best choice for proteomic analysis of mango peel.

PSF contacts exon 7 of SMN2 pre-mRNA to promote exon 7 inclusion.

Spinal muscular atrophy (SMA) is an autosomal recessive genetic disease and a leading cause of infant mortality. Deletions or mutations of SMN1 cause SMA, a gene that encodes a SMN protein. SMN is important for the assembly of Sm proteins onto UsnRNA to UsnRNP. SMN has also been suggested to direct axonal transport of ß-actin mRNA in neurons. Humans contain a second SMN gene called SMN2 thus SMA patients produce some SMN but not with sufficient levels. The majority of SMN2 mRNA does not include exon 7. Here we show that increased expression of PSF promotes inclusion of exon 7 in the SMN2 whereas reduced expression of PSF promotes exon 7 skipping. In addition, we present evidence showing that PSF interacts with the GAAGGA enhancer in exon 7. We also demonstrate that a mutation in this enhancer abolishes the effects of PSF on exon 7 splicing. Furthermore we show that the RNA target sequences of PSF and tra2ß in exon 7 are partially overlapped. These results lead us to conclude that PSF interacts with an enhancer in exon 7 to promote exon 7 splicing of SMN2 pre-mRNA.

SRSF2 promotes splicing and transcription of exon 11 included isoform in Ron proto-oncogene.

The product of proto-oncogene Ron is a human receptor for the macrophage-stimulating protein (MSP). Upon activation, Ron is able to induce cell dissociation, migration and matrix invasion. Exon 11 skipping of Ron pre-mRNA produces Ron△165 protein that is constitutively active even in the absence of its ligand. Here we show that knockdown of SRSF2 promotes the decrease of exon 11 inclusion, whereas overexpression of SRSF2 promotes exon 11 inclusion. We demonstrate that SRSF2 promotes exon 11 inclusion through splicing and transcription procedure. We also present evidence that reduced expression of SRSF2 induces a decrease in the splicing of both introns 10 and 11; by contrast, overexpression of SRSF2 induces an increase in the splicing of introns 10 and 11. Through mutation analysis, we show that SRSF2 functionally targets and physically interacts with CGAG sequence on exon 11. In addition, we reveal that the weak strength of splice sites of exon 11 is not required for the function of SRSF2 on the splicing of Ron exon 11. Our results indicate that SRSF2 promotes exon 11 inclusion of Ron proto-oncogene through targeting exon 11. Our study provides a novel mechanism by which Ron is expressed.

Upregulation of microRNA-200a associates with tumor proliferation, CSCs phenotype and chemosensitivity in ovarian cancer.

Ovarian cancer is a lethal gynecologic malignancy and always has a poor prognosis. Despite new treatments modalities, the long term outcomes had not been significantly improved in the past 30 years. Although microRNA-200a (miR-200a) has been reported to be a prognostic marker in ovarian cancer, it's exact role in ovarian cancer remain unclear. In this study, we inserted the response element of miR-200a in ovarian cancer cell line via lentivirus-mediated transgene in vitro, and qRT-PCR (real time quantitative reverse transcription PCR) assay confirmed that miR-200a was up regulated compared with control. Then colony-formation assay, cell cycle analysis, CCK8 assays in vitro and xenograft experiments in vivo were performed and verified that miR-200a promoted proliferation, while blocked the formation of tumor spheroids and reduced the ratio of SP (side population) cells in ovarian cancer. Finally, we invalidated that miR-200a significantly enhanced the chemosensitivity of paclitaxel but not cisplatin in both adherent culture and sphere culture. Taken together, we demonstrated that upregulation miR-200a promoted proliferation and inhibited CSCs phenotype in OVCAR-3 ovarian cancer cell line, combined with cell cycle-targeting drug paclitaxel could effectively eliminate the "side effects" of proliferation, and showed evidences that this strategy may be promising for ovarian cancer treatment.

Insulin receptor binding motif tagged with IgG4 Fc (Yiminsu) works as an insulin sensitizer to activate Akt signaling in hepatocytes.

Insulin resistance is a key feature of obesity and type 2 diabetes mellitus (T2DM). Interaction of insulin with the insulin receptor (IR) leads to both its auto-phosphorylation and phosphorylation of tyrosine residues on the IR substrate (IRS) proteins, initiating the activation of intracellular signaling cascades. The metabolic effects of IRS are known to be mediated through pathways involving phosphatidyl-inositol 3-kinase (PI-3K), which result in the activation of Akt signaling. The C-terminal region of the IR ectodomain is required to facilitate the conformational changes that are required for high-affinity binding to insulin. Furthermore, the CH2 and CH3 domains in the Fc fragments of immunoglobulins are responsible for their binding to the Fc receptor, which triggers transcytosis. In this study, we created a fusion peptide of the C-terminal end of the human IR ectodomain with the IgG4 Fc fragment, including an intervening polyG fragment to ensure enough space for insulin binding. We named this new peptide "Yiminsu", meaning an insulin sensitizer. The results of our analyses show that Yiminsu significantly facilitates insulin signaling via the activation of Akt in hepatocytes in a dose- and time-dependent manner. Further studies are required to determine whether Yiminsu can act as an insulin sensitizer.

Unveiling the longitudinal association between short sleep duration and the incidence of obesity: the Penn State Cohort.

OBJECTIVE: Several epidemiologic, longitudinal studies have reported that short sleep duration is a risk factor for the incidence of obesity. However, the vast majority of these studies used self-reported measures of sleep duration and did not examine the role of objective short sleep duration, subjective sleep disturbances and emotional stress. DESIGN: Longitudinal, population-based study. SUBJECTS: We studied a random sample of 815 non-obese adults from the Penn State Cohort in the sleep laboratory for one night using polysomnography (PSG) and followed them up for a mean of 7.5 years. Subjective and objective measures of sleep as well as emotional stress were obtained at baseline. Obesity was defined as a body mass index (BMI) ≥30 kg/ m(-2). RESULTS: The incidence of obesity was 15% and it was significantly higher in women and in individuals who reported sleep disturbances, shorter sleep duration and higher emotional stress. Significant mediating effects showed that individuals with subjective sleep disturbances who developed obesity reported the shortest sleep duration and the highest emotional stress, and that subjective sleep disturbances and emotional stress were independent predictors of incident obesity. Further analyses revealed that the association between short sleep duration, subjective sleep disturbances and emotional stress with incident obesity was stronger in young and middle-age adults. Objective short sleep duration was not associated with a significantly increased risk of incident obesity. CONCLUSION: Self-reported short sleep duration in non-obese individuals at risk of developing obesity is a surrogate marker of emotional stress and subjective sleep disturbances. Objective short sleep duration is not associated with a significant increased risk of incident obesity. The detection and treatment of sleep disturbances and emotional stress should become a target of our preventive strategies against obesity.

The economic burden of fracture patients with osteoporosis in western China.

UNLABELLED: To study the cost of osteoporotic fracture in China, we performed a prospective study and compared the costs of the disease in referral patients with fractures in three of the most common sites. Our results indicated that the economic burden of osteoporotic fracture to both Chinese patients and the nation is heavy. INTRODUCTION: This paper aims to study the cost of osteoporotic fracture in China and thus to provide essential information about the burden of this disease to individuals and society. METHODS: This prospective observational data collection study assessed the cost related to hip, vertebral, and wrist fracture 1 year after the fracture based on a patient sample consisting of 938 men and women. Information was collected using patient records, registry sources, and patient interviews. Both direct medical, direct non-medical, and indirect non-medical costs were considered. RESULTS: The annual total costs were highest in hip fracture patients (renminbi, RMB 27,283 or USD 4,330, with confidence interval (RMB 25715, 28851)), followed by patients with vertebral fracture (RMB 21,474 or USD 3,409, with confidence interval (RMB 20082, 22866)) and wrist fracture (RMB 8,828 or USD 1,401, with confidence interval (RMB 7829, 9827)). The direct medical care costs averaged approximately RMB 17,007 per year per patient, of which inpatient costs, drugs, and investigations accounted for the majority of the costs. Nonmedical direct costs were much less compared to direct healthcare costs and averaged approximately RMB 1,846. CONCLUSION: These results indicate that the economic burden of osteoporotic fracture to both Chinese patients and China was heavy, and the proportion of the costs in China demonstrated many similar features and some significant differences compared to other countries.

Associations between physical activity-related miRNAs and metabolic syndrome.

The aim of the study was to investigate the associations between physical activity (PA)-related miRNAs and metabolic syndrome (MetS). A case-control study was conducted in 209 subjects with MetS and 234 controls. The MetS was defined by the International Diabetes Foundation (IDF) criteria of 2005. Serum PA-related miRNAs were detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays. Association analysis was performed by logistic regression models. The expression levels of miR-126 and miR-130a were lower in the highest metabolic equivalent hours per week (MET-h/week) quartile than in the lowest quartile [miR-126: Q5 vs. Q1, median (5-95%), 1.67 (0.54, 2.45) vs. 1.35 (0.45, 2.45), p=0.012; miR-130a: Q5 vs. Q1, median (5-95%), 0.90 (0.44, 1.35) vs. 0.53 (0.26, 1.01), p<0.001]. However, miR-197 exhibited a trend with increased MET-h/week [Q5 vs. Q1, median (5-95%), 1.35 (0.45, 2.63) vs. 2.18 (0.87, 4.77), p=0.009]. MiR-126 increased MetS risk significantly while the effect of miR-197 was opposite (miR-126: OR=1.37, 95% CI 1.07-1.75; p=0.012; miR-197: OR=0.68, 95% CI 0.51-0.92; p=0.010). Individuals in the highest MET-h/week quartile had lower prevalence and odds rate of MetS compared with those in the lowest quartile (Q4 vs. Q1: OR=0.58, 95% CI 0.33-1.05; p for trend=0.026). However, further adjustment of both PA associated miRNAs abolished that association. All these results suggested that the association between PA and MetS risk might partly depend on miR-126 and miR-197.