[The effect of Ba Duan Jin on the balance of community-dwelling older adults: a cluster randomized control trial].

Objective: To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults. Methods: A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test. Results: A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95%CI: 2.23-3.88) points (P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95%CI: 4.03-5.37) points (P<0.001). Ba Duan Jin showed significant improvement (P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions: This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

Effects of rope skipping exercise on physical, cardiovascular fitness and exercise tolerance in adolescent students with moderate intellectual disability.

BACKGROUND: Adolescents with intellectual disabilities (ID) who live a sedentary lifestyle may lead to an increased risk of chronic cardiovascular disease in adulthood. The aim of this study is to investigate the effects of 8-week progressive rope skipping training on physical, cardiovascular fitness and exercise tolerance of high school students with moderate ID. METHODS: Thirty-four senior high school with ID (aged 15-18 years old) were randomised into experimental group received progressive skipping rope exercise (RS, n = 17) and control group no rope skipping exercise intervention group (CON, n = 17). The RS group were received progressive rope skipping exercise for 50 min each time, three times a week, for 8 weeks. The control group was not allowed to participate in intervention activities during the study period. The physical fitness, body composition, arterial stiffness index (ASI) and blood pressure were measured before and after the 8-week intervention. RESULTS: After the 8-week progressive skipping rope exercise intervention, the participants from the RS group increased in the 3-min step test, sit-up test, grip strength and sit and reach test, when compared to the baseline (P < 0.05). The RS group exhibited lower the area under curve of heart rate (HR) during post-exercise recovery (P < 0.05). The participants in the RS group showed significant decreases in systolic (SBP) and diastolic (DBP) blood pressure, mean arterial pressure (MAP) and HR when compared to the baseline (P < 0.05). Change SBP has moderate positive correlation with change ASI. CONCLUSIONS: The results of this experiment suggest that progressive rope skipping exercise might improve physical fitness and promote cardiovascular health, as well as enhance exercise tolerance for adolescent students with moderate ID.

[Clinical study of digital six-axis external fixation frame based on CT data for tibiofibular fractures].

Objective: To investigate the clinical effect of applying the digital six-axis external fixation frame based on CT data in the treatment of tibiofibular fractures. Methods: The clinical data of 43 patients with tibiofibular fractures treated by the self-developed digital six-axis external fixation frame based on CT data at Integrated Orthopedic Department of Traditional Chinese Medicine (TCM) and Western Medicine,HongHui Hospital from January 2018 to January 2021 were retrospective analysis.There were 27 males and 16 females,aged (36.0±9.4) years(range:25 to 50 years).AO classification:15 cases of 42A,11 cases of 42B, and 17 cases of 42C.There were 7 open fractures and Gustilo fracture classification:2 cases of type Ⅰ,4 cases of type Ⅱ,and 1 case of type Ⅲ.The two or three plane rings were connected with six connecting rods to form a complete six-axis external fixation frame,and the distal and proximal fracture blocks were connected to the distal and proximal rings by fixation pins,and the lengths of the six connecting rods needed to be adjusted were calculated by using the supporting software according to the CT data after surgery,and then the lengths of the connecting rods were adjusted one by one to complete the reduction of the fracture. The reduction accuracy of this six-axis external fixation brace was evaluated by measuring postoperative radiographs; postoperative recovery and complications were collected,the time of brace removal was recorded,and the function of the affected limb was evaluated according to the Johner-Wruhs score at the final follow-up. Results: Postoperative radiographs showed that all patients achieved satisfactory reduction with lateral displacement(M(IQR)) of 2.3(2.5) mm (range:0.3 to 7.3 mm),anteroposterior displacement of 2.1 (2.4) mm (range:0.3 to 5.7 mm),anteroposterior angulation of 2.5(2.4)°(range:0 to 5°),internal and external angulation of 2.1(1.5)°(range:0 to 4°), and no significant internal or external rotational deformity was detected on the exterior.On the second postoperative day,all patients were able to walk with partial weight-bearing on crutches. All 43 patients were followed up for more than 6 months,with a follow-up period of (33.3±7.3) weeks (range:24 to 42 weeks).The external fixation frame was removed after the fracture healed.The external frame was removed at 20(3)weeks (range:18 to 25 weeks) postoperatively. Up to the final follow up, no secondary fracture occurred in any of them.The Johner-Wruhs score of the affected limb at the last follow-up was excellent in 39 cases and good in 4 cases. Conclusion: The digital six-axis external fixator based on CT data for tibiofibular fractures has the advantages of precise reduction,firm fixation,simple operation,rapid fracture healing,and minimal trauma, which is a minimally invasive method for treating tibiofibular fractures,especially suitable for patients with poor skin and soft tissue conditions such as open injuries.

Effects of Exercise Alone or in Combination with High-Protein Diet on Muscle Function, Aerobic Capacity, and Physical Function in Middle-Aged Obese Adults: A Randomized Controlled Trial.

BACKGROUND: Obesity accelerates and exacerbates the age-related changes on muscle function and exercise capacity. In addition, the middle-aged population is often overlooked when talking about the prevention of sarcopenia. This study investigated the effects of exercise alone or in combination with a high-protein diet on muscle function and physical fitness in middle-aged obese adults. MATERIALS AND METHODS: Sixty-nine middle-aged (50-64 years old) obese adults were randomly assigned to one of the following groups: control group (C; n=23), exercise group (E; n=23) or exercise plus high-protein group (EP; n=23). Individuals within the E and EP groups received 12 weeks of exercise training; whereas, the individuals in the EP group also received a high-protein diet intervention (1.6g/kg/day). Individuals within the C group were asked to maintain their lifestyle for 12 weeks. Participants were evaluated before and after the intervention. Outcome measures included maximal exercise capacity, muscle function and functional physical performance. Analysis of covariance was used to determine the effects of the intervention. RESULTS: After the intervention, the E and EP groups had greater maximal work rate, peak oxygen consumption, and muscle power during muscle contractions at 180°/sec than that in the C group (P<0.05). The EP group, but not the E group, showed significant improvement in the sit-to-stand test and climbing stairs test than the C group after the intervention (P<0.05). Within group comparisons showed that the anaerobic threshold only increased in the EP group (+12% from pre-test). CONCLUSIONS: For middle-aged obese adults, exercise with a high-protein diet not only improved muscle power and exercise capacity but also enhanced their functional physical performance.

The impact of COVID-19 on subthreshold depressive symptoms: a longitudinal study.

AIMS: The coronavirus disease 2019 (COVID-19) pandemic represents an unprecedented threat to mental health. Herein, we assessed the impact of COVID-19 on subthreshold depressive symptoms and identified potential mitigating factors. METHODS: Participants were from Depression Cohort in China (ChiCTR registry number 1900022145). Adults (n = 1722) with subthreshold depressive symptoms were enrolled between March and October 2019 in a 6-month, community-based interventional study that aimed to prevent clinical depression using psychoeducation. A total of 1506 participants completed the study in Shenzhen, China: 726 participants, who completed the study between March 2019 and January 2020 (i.e. before COVID-19), comprised the 'wave 1' group; 780 participants, who were enrolled before COVID-19 and completed the 6-month endpoint assessment during COVID-19, comprised 'wave 2'. Symptoms of depression, anxiety and insomnia were assessed at baseline and endpoint (i.e. 6-month follow-up) using the Patient Health Questionnaire-9 (PHQ-9), Generalised Anxiety Disorder-7 (GAD-7) and Insomnia Severity Index (ISI), respectively. Measures of resilience and regular exercise were assessed at baseline. We compared the mental health outcomes between wave 1 and wave 2 groups. We additionally investigated how mental health outcomes changed across disparate stages of the COVID-19 pandemic in China, i.e. peak (7-13 February), post-peak (14-27 February), remission plateau (28 February-present). RESULTS: COVID-19 increased the risk for three mental outcomes: (1) depression (odds ratio [OR] = 1.30, 95% confidence interval [CI]: 1.04-1.62); (2) anxiety (OR = 1.47, 95% CI: 1.16-1.88) and (3) insomnia (OR = 1.37, 95% CI: 1.07-1.77). The highest proportion of probable depression and anxiety was observed post-peak, with 52.9% and 41.4%, respectively. Greater baseline resilience scores had a protective effect on the three main outcomes (depression: OR = 0.26, 95% CI: 0.19-0.37; anxiety: OR = 1.22, 95% CI: 0.14-0.33 and insomnia: OR = 0.18, 95% CI: 0.11-0.28). Furthermore, regular physical activity mitigated the risk for depression (OR = 0.79, 95% CI: 0.79-0.99). CONCLUSIONS: The COVID-19 pandemic exerted a highly significant and negative impact on symptoms of depression, anxiety and insomnia. Mental health outcomes fluctuated as a function of the duration of the pandemic and were alleviated to some extent with the observed decline in community-based transmission. Augmenting resiliency and regular exercise provide an opportunity to mitigate the risk for mental health symptoms during this severe public health crisis.

[Epidemiological characteristics of asymptomatic infection cases of COVID-19 in Guangdong province].

Objective: To analyze the epidemiological characteristics of the cases firstly reported as "asymptomatic infection of COVID-19" in Guangdong province. Methods: The follow-up observation method was used to continuously track and observe the cases firstly reported as "asymptomatic patients with COVID-19" in Guangdong province from January 14 to March 31, 2020. The epidemiological data of the cases were collected to analyze their epidemiological characteristics, outcome and influencing factors. Results: From January 14 to March 31, 2020, a total of 325 cases were firstly reported as "asymptomatic infections of COVID-19" in Guangdong province. The epidemic curve of asymptomatic infection cases was similar to that of confirmed cases, and it had two peaks. The first peak was from January 27 to February 5, and the second peak was from March 17 to March 26. Of the 325 cases, 184 (56.6%) were subsequently converted to confirmed cases. These cases were defined as incubation period asymptomatic infection cases. The age median of the cases was 40 years, and 93.5% (172/184) of the cases showed symptoms within 3 days after the first positive nucleic acid tests were conducted, and 141 (43.4%) of the 325 cases remained asymptomatic status until they were cured and discharged. They were inapparent infection cases, accounting for 8.6% (141/1 642) of those diagnosed with COVID-19 in Guangdong province during the same period. The age median of inapparent infection cases was 27 years. The median of the interval between the first positive nucleic acid test and discharge was 14 days. Up to 90.8% (138/141) of the inapparent infection cases were discharged for centralized medical observation within 28 days. The longest interval between the first positive nucleic acid test and the last positive nucleic acid test was 73 days. The positive rate of nucleic acid test was 0.3% in close contacts of inapparent infection cases and 2.2% in close contacts of incubation period asymptomatic infection cases. There were significant differences in age distribution and source of infection between incubation period asymptomatic infection cases and inapparent infection cases (P<0.05). Old age was the risk factor for the conversion of firstly reported asymptomatic infection cases to confirmed cases. Compared with the 0-19-year-old group, The patients aged 40-59 years and 60 years and above were more likely to become confirmed cases. The OR (95%CI) values were 2.730 (1.380-5.402) and 5.302 (2.199-12.783), and P values were 0.004 and 0.000, respectively. People being infected in China were more likely to become confirmed cases (OR=7.121, P=0.000). Conclusions: There were asymptomatic infection cases among patients diagnosed with COVID-19. The infectiousness of incubation period asymptomatic infection cases might be stronger than that of inapparent infection cases. The proportion of younger cases among asymptomatic infection cases was higher than that of the confirmed cases. Old age and domestic infection were the risk factors for the conversion of asymptomatic infection cases to confirmed cases, to which more attention should be paid. Further serological investigations are needed to provide a basis for the development of COVID-19 prevention and control strategies.

The efficacy and safety of topical rapamycin-calcitriol for facial angiofibromas in patients with tuberous sclerosis complex: a prospective, double-blind, randomized clinical trial.

BACKGROUND: The efficacy of topical rapamycin is well documented for tuberous sclerosis complex (TSC)-related facial angiofibromas (FAs). Calcitriol has been shown to lessen skin fibrosis and may be therapeutically beneficial to FAs. OBJECTIVES: To evaluate whether topical rapamycin-calcitriol combination is an effective and safe treatment for TSC-related FAs. METHODS: Fifty-two patients with TSC with FAs were enrolled in this prospective study including three 12-week periods. In period 1, either topical rapamycin 0·1% or calcitriol 0·0003% single-agent therapy vs. their combination was applied in a double-blind, left-right-randomized, split-face comparison. The primary outcome was the reduction of modified Facial Angiofibroma Severity Index (mFASI) at week 12. In period 2, the patients were reassigned to use on both cheeks the ointment that resulted in the better primary outcome in period 1. The treatment was discontinued in period 3 (week 25-36) and a follow-up mFASI was scored to evaluate the degree of recurrence. RESULTS: The mean changes in mFASI at week 12 compared with baseline were -0·92, -0·44 and -1·09 for rapamycin (P ≤ 0·001), calcitriol (P = 0·039) and rapamycin-calcitriol combination (P ≤ 0·001), respectively. Although rapamycin-calcitriol combination and rapamycin had similar statistically significant decreases of mFASI at week 12, rapamycin-calcitriol combination resulted in faster improvement in erythema, greater reduction of papule elevation and longer durability after discontinuing treatment than rapamycin alone. The treatments were well tolerated. CONCLUSIONS: This randomized clinical trial demonstrates that topical rapamycin-calcitriol combination therapy is an effective and safe regimen for TSC-related FAs. What is already known about this topic? Facial angiofibromas (FAs) cause substantial psychological distress in individuals with tuberous sclerosis complex (TSC), but invasive procedural treatments are not applicable to all patients. Topical rapamycin has been demonstrated as an effective and safe treatment regimen for TSC-related FAs. What does this study add? Compared with baseline (day 0), both topical rapamycin 0·1% and rapamycin 0·1%-calcitriol 0·0003% combination ointment achieved statistically significant reductions in modified Facial Angiofibroma Severity Index at week 12. Compared with rapamycin alone, extended use of the rapamycin-calcitriol combination regimen until week 24 showed more effectiveness in decreasing papule elevation and could maintain a longer therapeutic effect after treatment discontinuation. Linked Comment: Lee. Br J Dermatol 2020; 183:604-606.

Continued Elevation of Plasma IL-4 and IL-17 Predicts the Progression from VMC to DCM.

OBJECTIVE: To investigate plasma cytokines (interferon gamma, interleukin-4, and interleukin-17) in patients with viral myocarditis (VMC) and evaluate their predictive value in the progression from VMC to dilated cardiomyopathy (DCM). METHODS: A prospective, multicenter, observational study included 536 patients with newly diagnosed VMC admitted in cardiology departments of 24 tertiary super specialised university-affiliated hospitals in the China registry from January 2012 to June 2016. Demographics and clinical characteristics at baseline and after three months were collected, including laboratory blood tests, ECG, echocardiography, and drug treatment in each participating site. The plasma anti-viral antibodies (Abs), anti-heart autoimmune Abs, and cytokines were detected by ELISA. RESULTS: Of the 536 patients, 534 were included for analysis after two patients died in less than a month. The plasma levels of IFN-γ, IL-4, and IL-17 were continually higher in patients with incident DCM than in those without incident DCM at baseline, from the 1st month and the 3rd month; all had a P value of <0.0001. There was a positive correlation between IL-4 and LVEDd (r = 0.30, P < 0.0001) and between IL-17 and LVEDd (r = 0.11, P = 0.02). When all these covariates have entered the model simultaneously, elevated IL-4 and IL-17 were still significantly associated with DCM incidence. The RR (95% CI) of DCM incidence were 1.04 (1.02-1.06) for IL-4 and 5.24 (2.81-9.79) for IL-17. CONCLUSION: The continued elevation of plasma IL-4 and IL-17 in VMC patients were associated with a high incidence of DCM at three months, and these two cytokines were independent predictors for the progression from VMC to DCM.

Genetic alterations in primary melanoma in Taiwan.

BACKGROUND: Acral melanoma (AM) is the most common histopathological subtype of malignant melanoma in Asians. However, differences in the mutational profiles underlying AM and nonacral cutaneous melanoma (NAM) in Asians are not well understood. OBJECTIVES: To augment the understanding of the prevalence, patterns and associations of various mutations between different subtypes of melanoma. METHODS: We performed comprehensive genomic profiling of 409 cancer-associated genes, using next-generation sequencing, in 66 primary melanomas comprised of 45 AMs and 21 NAMs. RESULTS: Most of the AMs (n = 27/45; 60%), but only five of 21 (24%) NAMs, were triple wild-type (triple-WT) tumours. Compared with AMs, NAMs exhibited a significantly higher frequency of BRAF mutations. The frequencies of NRAS/KRAS mutations, cell-cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and gains of receptor tyrosine kinase genes were significantly higher in AMs. Ulceration was found at significantly higher rates in the AMs and NAMs with cell-cycle aberrations and gains of receptor tyrosine kinase genes. Notably, cell-cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma-specific survival in the 66 patients with melanoma and especially in the 45 patients with AM. Multivariate analysis showed that lymph node metastasis and cell-cycle aberrations were independent prognostic factors of melanoma-specific survival. CONCLUSIONS: This study strengthens our understanding of the patterns and clinical associations of oncogenic mutations in AMs and NAMs in Asians. What's already known about this topic? Mutation frequencies of driver genes vary between melanoma subtypes. Acral melanoma is the most common subtype of melanoma in Asians. KIT mutations and copy number variations occur more frequently in the acral subtype of melanoma than in the nonacral subtype What does this study add? NRAS/KRAS mutations, cell-cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and amplifications of receptor tyrosine kinase genes were significantly enriched in acral melanoma and could be potential targets for treatment. Melanomas with cell-cycle aberrations and gains in receptor tyrosine kinase genes were significantly more likely to contain ulceration. What is the translational message? Cell-cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma-specific survival. These observations should be explored further for future drug development.

[Pre- and post-orthotopic heart transplantation electrocardiogram characteristics of 998 patients].

Objective: To analyze pre- and post-operation electrocardiograms (ECGs) features of patients underwent orthotopic heart transplantation (OHT), and provide evidences for identifying and analyzing post OHT ECGs. Methods: Nine hundreds and ninty-eight pre- and post- OHT standard 12-leads ECGs from 110 consecutive patients, who underwent OHT in our hospital from May 2008 to May 2014, were analyzed. Results: The mean heart rate(HR)was (86.9±16.4) beats per minute before OHT, and (100.0±0.4) beats per minute after OHT. P wave's amplitude, duration, amplitude multiplied by duration of donor heart in lead Ⅱ were (0.124±0.069)mV, (111.1±17.2)ms, (14.34±9.51)mV·ms before OHT; (0.054±0.037)mV, (86.9±27.0)ms, (5.02±4.03)mV·ms at 1 month after OHT; (0.073±0.049)mV, (93.9±17.5) ms, (7.00±4.81)mV·ms at 6 years after OHT. ECGs rotation occurred in 83.64%(92/110) patients after OHT, and prevalence of clockwise rotation was 76.36%(84/110). Sinus tachycardia was evidenced in 99.09%(109/110) patients after OHT, and incomplete right bundle branch block was present in 60.91%(67/110) patients after OHT. Pseudo complete atrioventricular block mostly occurred at 2 days after OHT. Prevalence of double sinus rhythm was 27.95%(263/941) post OHT, 40% of them occurred between the 1st and the 2nd month post OHT; the atrial rate of recipient hearts was (104.0±10.2) beats per minucte between the 3rd and the 6th month post OHT, and was (95.3±4.2) beats per minucte between the 4th year and the 5th year. P wave's amplitude, duration, amplitude multiplied by duration of recipient heart in lead Ⅱ were (0.066±0.055) mV, (52.8±34.7) ms, (4.67±4.95) mV·ms at 1 month after OHT, (0.043±0.040)mV, (44.4±40.5) ms , (3.11±3.61) mV·ms between the 1st year and 2nd year after OHT. The absolute value of P-wave(originating from the donor heart) terminal force in chest leads increased in 48.99%(461/941) patients post OHT, the P-wave terminal force of V(1) , V(2) and V(3) were -0.044(-0.066, -0.028), -0.060(-0.087, -0.038), -0.035(-0.056, 0) mm·s. Notched P wave in chest leads was presented in 10.31%(97/941) patients post OHT. PR segment depression in chest leads occurred in 60.24%(100/166) patients between the 3rd month and the 6th month, the incidence of PR segment depression in V(1) , V(2) and V(3) was 21.04%(198/941), 37.41%(352/941) and 28.69%(270/941), respectively. Conclusions: OHT is related to significantly changed ECGs. The mean HR increased significantly after OHT, then decreased gradually after half a year to one year, but it was still higher than preoperative mean HR after five or six years; the P waves of donor heart were usually inconspicuous or small in first month after OHT, and they became bigger after 2 months, and their duration and amplitude then became relatively steady afterwards. ECGs rotation, especially the clockwise rotation, was common post OHT. A variety of arrhythmias originating from the donor heart including sinus tachycardia and incomplete right bundle branch block could be found. Pseudo complete atrioventricular block could also be found in the early phase after OHT. With the extension of time, the incidence of double sinus rhythm reduced gradually. The atrial rate and P wave of recipient heart presented with a tendency to become lower. The absolute value of P-waves(originating from the donor heart) terminal force in chest leads (mainly V(1), V(2) and V(3)) increased, notched P waves in chest leads (mainly V(1), V(2)) and PR segments depression in chest leads (mainly V(2), V(3) and V(4)) also belong to typical post OHT ECGs features.

Epidermal growth factor-induced ANGPTL4 enhances anoikis resistance and tumour metastasis in head and neck squamous cell carcinoma.

Epidermal growth factor (EGF) is important for cancer cell proliferation, angiogenesis and metastasis in many types of cancer. However, the mechanisms involved in EGF-induced head and neck squamous cell carcinoma (HNSCC) metastasis remain largely unknown. In this study, we reveal that angiopoietin-like 4 (ANGPTL4) plays an important role in the regulation of EGF-induced cancer metastasis. We showed that EGF-induced ANGPTL4 expression promoted anoikis resistance and cancer cell migration and invasion in HNSCC. In addition, depletion of ANGPTL4 inhibited EGF-induced cancer cell invasion. Autocrine production of EGF-induced ANGPTL4 regulated the expression of matrix metalloproteinases (MMPs). The induction of MMP-1 gene expression by ANGPTL4-activated integrin ß1 signalling occurred through the AP-1 binding site in the MMP-1 gene promoter. Furthermore, down-regulation of MMP-1 impeded EGF- and recombinant ANGPTL4-enhanced HNSCC cell migration and invasion. Depletion of ANGPTL4 significantly blocked EGF-primed extravasation and metastatic seeding of tumour cells and MMP-1 expression in lungs. However, no effect of ANGPTL4 on tumour growth was observed. These results suggest that EGF-induced expression and autocrine production of ANGPTL4 enhances HNSCC metastasis via the up-regulation of MMP-1 expression. Inhibition of ANGPTL4 expression may be a potential strategy for the treatment of EGFR-mediated HNSCC metastasis.

Particle size effect of curcumin nanosuspensions on cytotoxicity, cellular internalization, in vivo pharmacokinetics and biodistribution.

This study aimed to investigate the particle size effect on bioactivity, cellular internalization and bioavailability of curcumin (CUR) nanosuspension (CUR-NS). CUR-NSs of different particle sizes were prepared by two different anti-solvent precipitation methods. CUR-NS with the smallest size showed similar in vitro anticancer activity and bioavailability to the CUR solution, whereas nanosuspensions of larger particle sizes displayed higher in vitro cellular internalization and cytotoxicity, as well as higher in vivo AUC and slower clearance rate after i.v. administration in rats. CUR solution and different sized CUR-NSs reached the highest concentrations in the lung, followed by liver and spleen while the lowest concentration was observed in the brain after i.v. administration in mice. Specifically, CUR-NS of 70nm accumulated more in the brain, whereas CUR-NS of 200nm accrued more in liver and spleen. CUR-NS of 20nm displayed no significant biodistribution difference compared with CUR solution in all tissues.

Chromium chloride increases insulin-stimulated glucose uptake in the perfused rat hindlimb.

AIM: To determine the effect of chromium chloride (CrCl3 ) on healthy skeletal muscle glucose uptake in the absence and presence of submaximal insulin using the rat hindlimb perfusion technique. METHODS: Sprague-Dawley rats were randomly assigned to an experimental group: basal (Bas), chromium chloride (Cr), submaximal insulin (sIns) or chromium chloride plus submaximal insulin (Cr-sIns). RESULTS: Insulin significantly increased [H(3)]-2 deoxyglucose (2-DG) uptake in the gastrocnemius muscles. Additionally, Cr-sIns displayed greater rates of 2-DG uptake than sIns (Cr-sIns 6.86 ± 0.74 µmol g h(-1) vs. sIns 4.83 ± 0.42 µmol g h(-1)). There was no difference between Cr and Bas treatment groups. It has been speculated that chromium works to increase glucose uptake by increasing insulin signalling. We found that Akt and AS160 phosphorylation was increased in the sINS treatment group, while chromium treatment had no additional effect on Akt or AS160 phosphorylation in the absence or presence of insulin. Cr-sIns significantly increased plasma membrane GLUT4 concentration above that of sIns (Cr-sIns 72.22 ± 12.7%, sIns 53.4 ± 6.1%), but in the absence of insulin, chromium had no effect. CONCLUSION: Exposure of healthy skeletal muscle to chromium may increase skeletal muscle insulin-stimulated GLUT4 translocation and glucose uptake. However, these effects do not appear to result from enhanced insulin signalling proximal to AS160.

Increased risk of lichen simplex chronicus in people with anxiety disorder: a nationwide population-based retrospective cohort study.

BACKGROUND: The cingulate cortex is the main area in the brain involved in pruritus processing and is deactivated after scratching. Lichen simplex chronicus (LSC) is a common pruritic skin disorder characterized by skin lichenification following excessive scratching. Psychological factors may contribute to both the development and persistence of LSC. OBJECTIVES: To estimate the hazard ratio (HR) of LSC in people with anxiety disorders compared with the general population. METHODS: In this nationwide population-based retrospective cohort study we identified a total of 69 386 people, who formed the anxiety cohort, by using the Taiwan National Health Insurance Research Database from 2000 to 2009. The comparison cohort was composed of randomly selected people frequency matched for age (within 5-year intervals), sex and index date (the date of anxiety diagnosis) based on a 1 : 2 ratio. The risk of LSC was estimated as HRs and 95% confidence intervals (CIs) using the Cox proportional hazards model. RESULTS: After adjusting for age, sex and LSC-associated comorbidities, the people with anxiety had a 1·41-fold greater risk of developing LSC compared with the people in the comparison cohort (HR 1·41, 95% CI 1·30-1·52, P < 0·0001). In particular, individuals with obsessive-compulsive disorder had a significantly increased risk of developing LSC (HR 1·72, 95% CI 1·03-2·88, P = 0·0395). CONCLUSIONS: This study demonstrates that having an anxiety disorder is associated with an increased risk of LSC. Psychological factors were found to contribute to LSC. We recommend combining the management of LSC and psychological disorders to achieve favourable outcomes.

Differential effects of retinal degeneration on sleep and wakefulness responses to short light-dark cycles in albino mice.

This study characterizes the different response patterns of sleep and wakefulness (W) to short light-dark (LD) cycles in albino mice and examines whether retinal degeneration resulting from prolonged bright light treatment and/or rd/rd mutation alters such response patterns. Eight young male Institute for Cancer Research (ICR) mice with normal eyes, seven young male rd/rd Friend Virus B type (FVB) mice, six young ICR and five young rd/rd FVB mice receiving 48-h bright light treatment, and five older rd/rd FVB mice were implanted with skull and muscle electrodes to record sleep and W. All the mice were maintained in 12-h-12-h LD cycles at baseline and received 2 days of short LD cycle treatment, which included 5-min-5-min LD cycles for a total of 24 cycles presented 4h after lights-on and again 4h after lights-off. All the five mouse groups maintained photo-entrainment of sleep and W rhythms at the baseline and showed a preference for paradoxical sleep (PS) occurrence in the 5-min dark period and non-rapid eye movement sleep (NREMS) in the 5-min light period and a brief alerting effect of light onset on experimental days. Retinal degeneration rising from bright light treatment and/or genetic mutation failed to eliminate or reduce the response of PS and NREMS to short LD cycles, although it enhanced the LD contrast of W, i.e., bright light treatment prolonged the alerting effect of light and the rd mutation increased the suppressing effect of the dark on W. These results suggest that sleep responses to short LD cycles and the brief alerting effect of light were independent of the photoreceptors in the outer retina. Furthermore, the residual photoreceptors in the outer retina and/or the photosensitive cells in the inner retina may actively modulate the effect of light and dark signals on W.

Rapid pre-operative diagnosis of ileal hernia through the foramen of Winslow with multi-detector computed tomography, enabling successful laparoscopic reduction.

Internal hernias through the foramen of Winslow are extremely rare. Prompt diagnosis and early surgical reduction are vital to prevent bowel gangrene and avoid resection. We report a case of ileal hernia through the foramen of Winslow in a 48-year-old woman. She presented to the emergency department with acute epigastric pain, and rapid and definitive pre-operative diagnosis of internal hernia of ileum through the foramen of Winslow without ischaemia was made by means of multi-detector computed tomography. Emergency laparoscopic bowel reduction was performed. The postoperative course was uneventful, and the patient recovered rapidly.

Upregulated ankyrin repeat-rich membrane spanning protein contributes to tumour progression in cutaneous melanoma.

BACKGROUND: We have previously demonstrated that overexpression of ankyrin repeat-rich membrane spanning (ARMS) protein facilitates melanoma formation via conferring apoptotic resistance. This study aims to investigate whether ARMS contributes to melanoma progression. METHOD: Using immunohistochemistry, we graded the expression level of ARMS in 54 cases of primary melanoma and 46 cases of metastatic melanoma. The immunointensity of ARMS was statistically correlated with individual clinicopathological characteristics. By RNA interference, stable melanoma cell clones with ARMS-knockdown were constructed, and were used for in vitro scratch wound, transwell invasion assays, and in vivo lung metastasis experiment. RESULTS: Stronger immunointensity of ARMS was observed mostly in melanomas with Breslow tumour thickness >1.0 mm (Fisher's exact test, P=0.002) or with nodal metastasis (Fisher's exact test, P=0.026), and was correlated with a worse overall survival in melanoma patients (log-rank test, P=0.04). Depletion of ARMS inhibited migration, invasion, and metastatic potential of melanoma cells in vitro and in vivo. Moreover, ARMS mediated melanoma cell migration and invasion through activation of the extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signalling pathway. CONCLUSION: Ankyrin repeat-rich membrane spanning expression, conjunctly with tumour thickness or ulceration, may serve as a prognostic factor in patients with cutaneous melanoma.

Relationship between plasma inflammatory markers and plaque fibrous cap thickness determined by intravascular optical coherence tomography.

OBJECTIVE: The purpose of this study was to evaluate the relationship between human plaque fibrous cap thickness detected by intravascular optical coherence tomography (OCT) and the plasma levels of inflammatory factors in patients with coronary artery disease (CAD). METHODS AND RESULTS: OCT was used to measure the fibrous cap thickness of coronary artery atherosclerotic plaques in patients with acute myocardial infarction (AMI), unstable angina pectoris (UAP) and stable angina pectoris (SAP). Plasma levels of inflammatory factors including highly sensitive C-reactive protein (hs-CRP), IL-18 and tumour necrosis factor alpha (TNFalpha) were detected by ELISA, and peripheral white blood cell (WBC) counts were performed. The results demonstrated that the plasma levels of inflammatory factors and WBC count were correlated inversely with fibrous cap thickness (r = -0.775 for hs-CRP, r = -0.593 for IL-18, r = -0.60 for TNFalpha and r = -0.356 for WBC count). Patients with cap thickness less than 65 microm (defined to be thin cap fibroatheromas; TCFA) had higher plasma levels of inflammatory factors as well as WBC counts than those with thicker fibrous caps. Receiver operator characteristic (ROC) curves for hs-CRP, IL-18, TNFalpha and WBC count, which displayed the capability of prediction about TCFA, showed the area under the curves were 0.95, 0.86, 0.79 and 0.70 (p<0.05), respectively. ROC curve analysis confirmed that an hs-CRP cut-off at 1.66 mg/l would detect TCFA with a sensitivity of 96% and a specificity of 90%, and was the strongest independent predictor of TCFA. CONCLUSION: There is an inverse linear correlation between fibrous cap thickness and plasma levels of inflammatory markers. The plasma hs-CRP concentration is the strongest independent predictor of TCFA.