Wide surgical margins improve prognosis for HCC with microvascular invasion.

OBJECTIVE: Hepatocellular carcinoma (HCC) is the sixth leading cause of malignant tumors worldwide. Liver resection is a pivotal treatment modality for HCC. Surgical margin plays an important role in decreasing recurrence and improving prognosis for HCC patients. MATERIALS AND METHODS: This paper aimed to perform a systematic review of the literature in regard to surgical margin in HCC patients with microvascular invasion (MVI). RESULTS: Residual MVI due to insufficient surgical margins is the main origin of postoperative recurrence and metastasis in HCC patients. A wide surgical margin (WSM) significantly improves oncological outcomes and long-term survival in HCC patients with MVI. Progress in the preoperative prediction of MVI may contribute to precise surgical decision-making in the future. CONCLUSIONS: WSM was associated with better outcomes in HCC patients with MVI. WSM is recommended for well-preserved liver function HCC patients who are predicted to have a high risk of MVI preoperatively.

Promoting physical activity through exergaming in young adults with intellectual disabilities: a pilot study.

Various health problems of people with intellectual disabilities (ID) are associated with their physical inactivity. The present study aimed at the understanding of physiological and psychological responses toward exergaming in seven young adults with mild to moderate ID after a single-session and a multiple-session condition, respectively. Their heart rate (HR), the rating of perceived exertion (RPE), and physical activity enjoyment scale (PACES) were measured on control and exergaming sessions. The significant increased HR, which may represent the increased physical activity levels that led to energy expenditure, was observed after a single-session and a multiple-session condition. In addition, the significant increase in RPE and PACES were evident after a single-session condition but a multiple-session condition. The feeling of physical fatigue seems to be distracted by external motivators (e.g. music). However, the positive affectivity to exercise was not noted when exercise was scheduled as their daily routines. This phenomenon might explain the high prevalence of physical inactivity among this population.

Experimental semi-autonomous eigensolver using reinforcement learning.

The characterization of observables, expressed via Hermitian operators, is a crucial task in quantum mechanics. For this reason, an eigensolver is a fundamental algorithm for any quantum technology. In this work, we implement a semi-autonomous algorithm to obtain an approximation of the eigenvectors of an arbitrary Hermitian operator using the IBM quantum computer. To this end, we only use single-shot measurements and pseudo-random changes handled by a feedback loop, reducing the number of measures in the system. Due to the classical feedback loop, this algorithm can be cast into the reinforcement learning paradigm. Using this algorithm, for a single-qubit observable, we obtain both eigenvectors with fidelities over 0.97 with around 200 single-shot measurements. For two-qubits observables, we get fidelities over 0.91 with around 1500 single-shot measurements for the four eigenvectors, which is a comparatively low resource demand, suitable for current devices. This work is useful to the development of quantum devices able to decide with partial information, which helps to implement future technologies in quantum artificial intelligence.

Improvement in lip appearance (lateral and frontal aspects) following mandibular setback surgery.

INTRODUCTION: The post-operative facial profile is critical for patients who undergo orthognathic surgery. The present study investigated the improvement in lip appearance (lateral and frontal aspects) following mandibular setback surgery. MATERIAL AND METHODS: Thirty-one patients with mandibular prognathism underwent mandibular setback surgery. Lateral and posteroanterior cephalograms were obtained before surgery (T0) and more than 1 year after surgery (T1). The landmarks (soft and hard tissues) and linear distances were compared by statistical analysis. RESULTS: The lateral cheilion (Ch), point B (B), and pogonion (Pog) were significantly setbackin the horizontal plane: 5.59, 11.49, and 12.35 mm, respectively. In the vertical plane, B and Pog did not move significantly. The Ch moved significantly downward by 3.23 mm on average. The setback ratios of soft tissue/hard tissue, soft tissue of B/B, and soft tissue of Pog/Pog were 0.96. The Ch/Pog ratio was 0.45. The width of the frontal Ch was significantly reduced by 3.17 mm. CONCLUSIONS: The relationship between the corresponding soft and hard tissues of the chin was approximately 1. The relationship between the lip corner and chin bone was nearly 50%. The width of the lip corner was also significantly reduced.

Appearance on face reading (cheek line) after orthognathic surgery.

The cheek line (face reading) is an aesthetic element of the facial profile. The purpose of our study was to investigate the changes in the cheek line after mandibular setback surgery. Forty patients (20 female and 20 male, mean (SD) age 22 (5) years) were diagnosed with mandibular prognathism and treated by intraoral vertical ramus osteotomy alone. Cephalograms were obtained before operation (T1), at least a year postoperatively (T2), and final surgical changes over a year (T2-T1). The cheek line and landmarks (soft and hard tissues) were compared using the paired t test. The hypothesis was that the cheek line did not change significantly after mandibular setback. At the time of the final follow-up (T2-T1), the mean (SD) horizontal setback of pogonion (Pog) was 12.3 (3.5) mm for women and 11.7 (4.3) mm for men. The ratios of soft:hard tissue, labrale inferius:incisor inferius, labiomental sulcus:point B, soft tissue Pog:Pog, and cheek point:Pog in women were 0.96, 0.98, 0.98, and 0.08, and in men 0.91, 1.01, 0.94, and 0.13, respectively. The nasolabial and cervicomental angles in women were significantly increased by 11.1° and 11.4°, respectively, and in men the nasolabial angle was significantly increased by 11.1° and the mentolabial angle reduced by 9.9°. The cheek line (T2-T1) was moved significantly forwards. The hypothesis was therefore rejected. In conclusion, the cheek line was advanced significantly after isolated mandibular setback.

Efficacy and safety of combination therapy with vildagliptin and metformin versus metformin uptitration in Chinese patients with type 2 diabetes inadequately controlled with metformin monotherapy: a randomized, open-label, prospective study (VISION).

AIMS: To compare the efficacy and safety of combination of vildagliptin and metformin therapy with metformin uptitration in Chinese patients with type 2 diabetes (T2DM) inadequately controlled with low-dose metformin. METHODS: In this 24-week prospective, randomized, multicentre, open-label study, patients with T2DM inadequately controlled with metformin ≤1000 mg daily were divided 1 : 1 : 1 : 1 into four prespecified subgroups based on age and body mass index (BMI). Patients in each subgroup were randomized 5 : 1 to receive either vildagliptin (50 mg twice daily) plus metformin [500 mg twice daily; vildagliptin and low-dose metformin (VLDM) group] or metformin uptitration [1000 mg twice daily; high-dose metformin (HDM) group]. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline at week 24. The key secondary endpoints included percentage of patients achieving target HbA1c without adverse gastrointestinal (GI) events and mean change in fasting plasma glucose (FPG) from baseline to week 24. RESULTS: A total of 3084 patients were randomized. HbA1c reduction of 0.54% at week 24 in the VLDM group was non-inferior and statistically superior compared with 0.40% in the HDM group (P < 0.0001). VLDM's non-inferiority to HDM was confirmed in the four subgroups and its superiority was shown for all subgroups (p < 0.05) except for the subgroup of patients aged <60 years with a BMI of ≥24 kg/m(2) . Compared with HDM, VLDM significantly increased the percentage of patients achieving HbA1c ≤6.5% and HbA1c ≤6.5% without GI events. FPG levels in the VLDM group were lower at week 24 numerically than in the HDM group. The two treatment arms had similar safety profiles. CONCLUSIONS: VLDM was non-inferior and statistically superior to HDM in glycaemic control in Chinese patients with T2DM inadequately controlled with low-dose metformin.

Life and death of human vascular endothelial cells by stimulation with free fatty acids through death receptors.

Diabetic individuals may have elevated levels of serum free fatty acids and may exhibit injury to the vascular endothelial cells. This study was undertaken to determine the relationship between various free fatty acids (FFAs) and vascular endothelial cell injury and the molecular mechanisms linking FFA-induced vascular endothelial cells injury or protection. We observed the survival of HUVECs exposed to different FFAs, and our results revealed that the effects of various FFAs on the cell survival of HUVECs were significantly different. Palmitic acid (PA) markedly decreased the HUVEC survival rate in a time- and dose-dependent manner, but arachidonic acid (AA) significantly increased the cell survival rate and could partially prevent cellular apoptosis induced by PA. Interestingly, PA and AA could activate the same target receptor, TNF-R1. PA induced the apoptosis of HUVECs by initiating the death pathway (TNF-R1/TRADD/caspases 8 pathway), whereas AA enhanced cell survival to protect vascular endothelial cells by activating the survival pathway (TNF-R1/RIP/NF-κB 50/NF-κB 65).

Hip fracture after first-ever stroke: a population-based study.

OBJECTIVES: The aim of this study is to estimate the risk of hip fracture after first-ever stroke, using a nationwide population-base data set and a retrospective cohort design. MATERIALS AND METHODS: The cohort study involved 18,413 patients surviving a first-ever stroke during the 12-year period from 1997 to 2008. Another 18,413 control subjects were randomly selected with adjustment for age, gender and enrolled year. Stroke type, duration between stroke and hip fracture, six comorbidities and five categories of medication prior to hip fracture were investigated. RESULTS: This study found that 788 (4.3%) subjects in the study group suffered from hip fracture, with a 4.2 years median time frame (interquartile range = 1.8-7.1). In the control group, 492 subjects (2.7%) suffered from hip fracture during a 4.8 years median time frame (interquartile range = 2.0-7.5). The relative risk of hip fracture for stroke was increased in the first four years (1.4-2.4) and gradually declined to the level of the general population. Cox regression analysis showed osteoporosis-related factors, including ageing, female and antidepressants, significantly increased hip fracture risk (hazard ratios 1.89, 1.57, 1.92). CONCLUSIONS: These findings imply that osteoporosis may play a major role in the occurrence of hip fracture in the first four years after a first-ever stroke. Early intervention to prevent bone loss should be regarded as an important part in stroke management, especially in older females, and should be sustained for four years at least. The benefit of antidepressants in stroke patients should be weighed against the increased risk of hip fracture.

Synthesis and anticonvulsant and antidepressant activity of 2-(5-bromo-2,3-dioxoindolin)-N-substituted phenylacetamide derivatives.

16 2-(5-bromo-2,3-dioxoindolin-1-yl)-N-substituted phenylacetamide derivatives were synthesized. The chemical structures of the compounds were proved by IR, 1H-NMR, 13C-NMR, Mass spectrometric data and microanalyses. The antidepressant activities of the compounds were investigated by Porsolt's behavioural despair (the forced swimming test) in mice. 2-(5-bromo-2,3-dioxoi-ndolin-1-yl)-N-(2-fluorophenyl)acetamide(4f), 2-(5-bromo-2,3-dioxoindolin-1-yl)-N-(3-chlorophenyl)acetamide(4j), 2-(5-bromo-2,3-dioxoindolin-1-yl)-N-(4-bromophenyl)acetamide(4m) reduced 54.9-44.6% duration of immobility times at 100 mg · kg-1 dose level. Anticonvulsant activities were determined by substances pentylenetetrazloe(metrazol)(anti-PTZ) test, and neurotoxicities were determined by the rotarod toxicity test in mice. 12 synthesized compounds were found protective against PTZ at 100 mg ∙ kg-1 dose level.

Profile of vildagliptin in type 2 diabetes: efficacy, safety, and patient acceptability.

Vildagliptin is a selective and potent dipeptidyl peptidase-4 inhibitor that improves glycemic control by inhibiting the degradation of both endogenous glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. This article is a comprehensive review of the safety and efficacy of vildagliptin in patients with type 2 diabetes. Clinical evidence has proven that it effectively decreases hemoglobin A1c with a low risk of hypoglycemia and is weight neutral. The addition of vildagliptin to metformin improves glucose control and significantly reduces gastrointestinal adverse events, particularly in patients inadequately controlled with metformin monotherapy. Its long-term advantages include preservation of ß-cell function, reduction in total cholesterol, decrease in fasting lipolysis in adipose tissue, and triglyceride storage in non-fat tissues. Vildagliptin is well tolerated with a low incidence of AEs, and it does not increase the risk of cardiovascular/cerebrovascular (CCV) events. It can be taken before or after meals, and has little drug interaction, thus it will be well accepted.

Diffuse large cell non-Hodgkin lymphoma with pituitary and bilateral adrenal involvement.

We describe an elderly male patient who presented with fever of unknown origin and refractory hyponatraemia. Following (18) fluorine-fluorodeoxyglucose positron emission tomography/computed tomography scan and core adrenal biopsy, the diagnosis of diffuse large B-cell non-Hodgkin lymphoma with pituitary and bilateral adrenal involvement was confirmed. After chemotherapy, his symptoms resolved, and all the lesions shrank significantly.

Dual-task study of cognitive and postural interference: a preliminary investigation of the automatization deficit hypothesis of developmental co-ordination disorder.

BACKGROUND: The purpose of this study was to investigate whether children with developmental co-ordination disorder and balance problem (DCD-BP) had greater problems than controls in performing a primary balance task while concurrently completing different cognitive tasks varying in oral or listening cognitive complexity, as well as to investigate the automatization deficit hypothesis of DCD-BP. METHODS: Children with DCD-BP (n= 39), along with age-matched control counterparts (n= 39), were placed on automatic processing situation under dual-task conditions. All children were required to perform a primary task, five dual-task paradigms (oral counting task, auditory-verbal reaction task, auditory-choice reaction task, auditory-memory task and articulation alone) and an eyes-closed balancing task. RESULTS: In the primary task condition, the differences were not statistically significant (P= 0.393) between children with and without DCD-BP. However, children with DCD-BP were significantly more impaired on three of five dual-task conditions (oral counting task: P= 0.003; auditory-verbal reaction task: P= 0.011; auditory-memory task: P= 0.041) compared with the single-task situation, with the exception of the auditory-choice reaction task (P= 0.471) and articulation alone (P= 0.067). CONCLUSIONS: These results suggest that children with DCD-BP were more cognitively dependant and may have an automatization deficit.

Mechanism of transcriptional regulation of LRP16 gene expression by 17-beta estradiol in MCF-7 human breast cancer cells.

LRP16 gene expression is induced by 17-betaestradiol (E2) via estrogen receptor alpha (ERalpha) in MCF-7 human breast cancer cells. A previous study also demonstrated that ectopic expression of LRP16 gene promoted MCF-7 cell proliferation. To explore the mechanism of hormone-induced LRP16 gene expression, the LRP16 gene promoter region (-2600 to -24 bp upstream of the LRP16 gene translation starting site) was analyzed in the present study by using different 5'-truncated constructs, and a luciferase reporter. The 5'-flanking sequence of -676 to -24 bp (pGL3-S5) was found to be E2-responsive. After exchange of the fragment from -213 to -24 bp with the TK gene proximal promoter region in pGL3-S5, E2 still induced reporter gene activity in MCF-7 and HeLa cells. Sequence analysis showed that the pGL3-S6 (-676 to -214) sequence contains two motifs that may contribute to E2-induced transactivation; namely, an estrogen-responsive element (ERE) half-site/Sp1 at -246 to -227 bp and an E-box site at -225 to -219 bp. Further deletion and mutation analysis of these two motifs indicated that both the 1/2 ERE and Sp1 binding sites were required for E2 action, while E-box deletion did not affect the luciferase activity in MCF-7 and HeLa cells. The results of gel mobility shift and chromatin immunoprecipitation assays confirmed that both ERalphaand Sp1 were required for hormone-induced transactivation, which involved both ERalphaand Sp1 directly binding to DNA. Taken together, these findings suggest that ERalphaand Sp1 play a role in activation of the human LRP16 gene promoter.

Orlistat in the treatment of overweight or obese Chinese patients with newly diagnosed Type 2 diabetes.

AIMS: Orlistat promotes weight loss in overweight and obese patients with Type 2 diabetes receiving hypoglycaemic treatment, but has not been investigated in patients with newly diagnosed and previously untreated Type 2 diabetes. We evaluated the efficacy of 24 weeks' treatment with orlistat, combined with a mildly reduced-calorie diet, on weight loss and glycaemic control in overweight and obese patients with newly diagnosed and previously untreated Type 2 diabetes. METHODS: A total of 249 Chinese patients (body mass index 25-40 kg/m2) with recently diagnosed Type 2 diabetes were randomized to placebo (n=124) or orlistat 120 mg (n=125) three times daily; all patients followed a mildly reduced-calorie diet. Patients had HbA1c 6.5-8.5% (mean 7.3%) and had never received any glucose-lowering medication. RESULTS: Orlistat-treated patients achieved significantly greater weight loss at the study end than placebo-treated patients (-5.4 vs. -2.4 kg; P<0.0001). More orlistat than placebo patients lost>or=5% (60.5 vs. 26.8%; P<0.0001) and >or=10% of their body weight (20.2 vs. 4.9%; P=0.0002). A significantly greater decrease in HbA(1c) from baseline was obtained with orlistat than placebo (-1.0 vs. -0.6%; P=0.0008). Orlistat-treated patients achieved a significantly greater decrease in fasting plasma glucose (-1.3 vs. -0.5 mmol/l; P=0.0003) and in the 2-h oral glucose tolerance test (-4.1 vs. -1.4 mmol/l; P<0.0001) than placebo recipients. Also, more orlistat- than placebo-treated patients improved from diabetic status to normal or impaired glucose tolerance (44.3 vs. 32.5%; P=0.0763) after 24 weeks. Orlistat also produced improvements in lipid profiles and waist circumference. CONCLUSIONS: In combination with a mildly reduced-calorie diet, orlistat significantly reduces body weight, and improves glycaemic control and several cardiovascular risk factors in overweight and obese Chinese patients with newly diagnosed Type 2 diabetes.

Up-regulation of LRP16 mRNA by 17beta-estradiol through activation of estrogen receptor alpha (ERalpha), but not ERbeta, and promotion of human breast cancer MCF-7 cell proliferation: a preliminary report.

LRP16 is a novel gene cloned from lymphocytic cells, and its function is not known. The expression level of LRP16 mRNA was up-regulated by estrogen in breast cancer MCF-7 cells based on the computed aided serial analysis of gene expression (SAGE) analysis. In this study, we investigate the effect of 17beta-estradiol (17beta-E(2)) on the expression of LRP16 mRNA and the effects of overexpression of LRP16 on the proliferation of cultured MCF-7 cells and the possible mechanisms involved. The expression level of LRP16 mRNA induced by 17beta-E(2) was determined by Northern blot analysis. LRP16 promoter-controlled luciferase expression vector (pGL3-S(0)) was co-transfected with various nuclear receptors, including estrogen receptor alpha and beta (ERalpha and ERbeta), glucocorticoid receptor alpha (GRalpha), androgen receptor (AR) and peroxisome-proliferator activated receptor gamma and alpha (PPARgamma and PPARgamma) into COS-7 cells, and the relative luciferase activity was measured using Dual-luciferase report assay systems. The effect of overexpression of LRP16 on MCF-7 proliferation was examined by the Trypan Blue exclusion method, and the cell cycle was analyzed by flow cytometry. The expression levels of cyclin E, p53 and p21(WAF1/CIP1) proteins were determined by Western blot analysis. The results showed (1) 17beta-E(2) induced a five- to eightfold increase in LRP16 mRNA levels in MCF-7 cells; (2) the relative luciferase activities in the COS-7 cells co-transfected by pGL3-S(0) and ERalpha or AR were 7.8-fold and 11-fold respectively of those in the control cells transfected by pGL3-S(0) alone; (3) overexpression of LRP16 stimulated MCF-7 cell proliferation, and the numbers of cells in the S-phase of the cell cycle in cells transfected with LRP16 increased about 10% compared with the control cells; and (4) cyclin E levels were much higher in cells with overexpression of LRP16 than in the control cells, while the expression levels of p53 and p21(WAF1/CIP1) were not different between the two groups of cells. From these results we concluded that estrogen up-regulates the expression level of LRP16 mRNA through activation of ERalpha and that overexpression of LRP16 promotes MCF-7 cell proliferation probably by increasing cyclin E.

Addition of rosiglitazone to existing sulfonylurea treatment in chinese patients with type 2 diabetes and exposure to hepatitis B or C.

The effects of adding rosiglitazone to existing sulfonylurea (SU) treatment have not previously been studied in Chinese patients with type 2 diabetes and no known pre-existing hepatic impairment. Patients were randomized to receive rosiglitazone 2 mg twice daily (R4 + SU) or 4 mg twice daily (R8 + SU) or placebo (SU + P) for 24 weeks in addition to existing SU treatment. Most patients were taking concomitant glibenclamide (34%) or gliclazide (25%). Changes in glycosylated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), and plasma insulin concentrations were measured. Of the 530 patients enrolled (45% male, mean age 59 years), 105 were in the SU + P group, 215 in the R4 + SU group, and 210 in the R8 + SU group. The mean baseline HbA(1c) was 9.8%, and FPG was 183.8 mg/dL. Compared with placebo, addition of rosiglitazone (2 or 4 mg twice daily) produced significant decreases in mean HbA(1c) (1.04% and 1.44%, respectively; p < 0.0001) and FPG (21.6 and 36.0 mg/dL, respectively; p < 0.0001). There were statistically significant (p < 0.0001) reductions from baseline in insulin concentration of 23.3 and 30.4 pmol/L in the R4 + SU and R8 + SU groups, respectively. Despite the high prevalence of seropositivity for hepatitis B and/or C at baseline (56%), there was no evidence of hepatotoxicity. No clinically significant changes in routine hematology, biochemistry, or electrocardiogram were observed. The addition of rosiglitazone to SU produced clinically significant improvements in glycemic control in Chinese patients with type 2 diabetes. Rosiglitazone plus SU was well tolerated irrespective of hepatitis B and C serological status.