Objective To investigate the dosimetric differences between volumetric modulated arc therapy (VMAT) with a flattening filter (FF) and flattening filter-free (FFF) VMAT in fractionated stereotactic radiotherapy for brain metastases. Methods Seventeen patients with brain metastases were divided into FF-VMAT group (VMAT plans with the FF mode) and FFF-VMAT group (VMAT plans with the FFF mode). The two groups were compared in terms of target volume dose parameters (D_98%, D_2% and D_mean), the conformal index (CI), the gradient index (GI), the gradient, normal brain tissue dose parameters (V_5Gy, V_10Gy, V_12Gy and D_mean), monitor units, and beam-on time. Results Compared with the FF-VMAT group, the FFF-VMAT group had significantly lower GI (3.33 ± 0.37 vs 3.27 ± 0.35, P = 0.001), a significantly lower gradient [(0.85 ± 0.20) cm vs (0.84 ± 0.19) cm, P = 0.002], a significantly shorter beam-on time [(177.05 ± 62.68) s vs (142.71 ± 34.59) s, P = 0.001], and significantly higher D_2% [(65.69 ± 2.15) Gy vs (66.99 ± 2.03) Gy, P = 0.001] and D_mean [(58.77 ± 1.60) Gy vs (59.95 ± 1.43) Gy, P <0.001]. There were no significant differences in the CI, the D_98% of the target volume, the V_5Gy, V_10Gy, V_12Gy and D_mean of the normal brain tissue, and monitor units between FFF-VMAT and FF-VMAT. Conclusion FFF-VMAT can better protect the normal tissue around the target volume, reduce the beam-on time, and improve treatment efficiency.

Objective    To explore risk factors associated with mortality and restenosis after the surgery for congenital pulmonary venous stenosis (CPVS) combined with congenital heart disease. Methods    From May 2007 to August 2019, 58 patients received surgical relief of CPVS combined with congenital heart disease, including 24 males and 34 females, aged 17.2±26.3 months, weighing 8.8±8.2 kg. Endpoints were death and restenosis, and the risk factors were analyzed. A univariate and multivariate risk analyses were performed. Results    Preoperative pulmonary venous stenosis severity score (PVSSS) was 4.5±2.7. Average pulmonary vein counts with CPVS was 1.9±1.0. There were 2 (3.4%) early deaths. The mean follow-up time was 2-145 (49.8±40.0) months. The 1-, 2-, 3- and 5-year overall survival rates were 86.7%, 81.3%, 78.5% and 73.6%, respectively, and the pulmonary venous restenosis-free rates were 79.6%, 68.5%, 68.5% and 68.5%, respectively. Preterm birth was an independent risk factor for mortality. The pulmonary venous peak flow rate ≥ 1.2 m/s at discharge was an independent risk factor for mortality and restenosis. Conclusion    The prognosis of CPVS is still poor. Postoperative residual stenosis at discharge is an independent risk factor for death and restenosis.

Given the opposing effects of Akt and AMP-activated protein kinase (AMPK) on metabolic homeostasis, this study examined the effects of deletion of Akt2 and AMPKα2 on fat diet-induced hepatic steatosis. Akt2–Ampkα2 double knockout (DKO) mice were placed on high fat diet for 5 months. Glucose metabolism, energy homeostasis, cardiac function, lipid accumulation, and hepatic steatosis were examined. DKO mice were lean without anthropometric defects. High fat intake led to adiposity and decreased respiratory exchange ratio (RER) in wild-type (WT) mice, which were ablated in DKO but not Akt2−/− and Ampkα2−/− mice. High fat intake increased blood and hepatic triglycerides and cholesterol, promoted hepatic steatosis and injury in WT mice. These effects were eliminated in DKO but not Akt2−/− and Ampkα2−/− mice. Fat diet promoted fat accumulation, and enlarged adipocyte size, the effect was negated in DKO mice. Fat intake elevated fatty acid synthase (FAS), carbohydrate-responsive element-binding protein (CHREBP), sterol regulatory element-binding protein 1 (SREBP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), peroxisome proliferator-activated receptor-α (PPARα), PPARγ, stearoyl-CoA desaturase 1 (SCD-1), phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase), and diglyceride O-acyltransferase 1 (DGAT1), the effect was absent in DKO but not Akt2−/− and Ampkα2−/− mice. Fat diet dampened mitophagy, promoted inflammation and phosphorylation of forkhead box protein O1 (FoxO1) and AMPKα1 (Ser485), the effects were eradicated by DKO. Deletion of Parkin effectively nullified DKO-induced metabolic benefits against high fat intake. Liver samples from obese humans displayed lowered microtubule-associated proteins 1A/1B light chain 3B (LC3B), Pink1, Parkin, as well as enhanced phosphorylation of Akt, AMPK (Ser485), and FoxO1, which were consolidated by RNA sequencing (RNAseq) and mass spectrometry analyses from rodent and human livers. These data suggest that concurrent deletion of Akt2 and AMPKα2 offers resilience to fat diet-induced obesity and hepatic steatosis, possibly through preservation of Parkin-mediated mitophagy and lipid metabolism.

BACKGROUND Hepatopulmonary syndrome (HPS) is not uncommon in the setting of liver disease, especially in liver cirrhosis patients. The prevalence of HPS in liver cirrhosis patients varies from 4% to 47%.[1-3] About the definition of HPS, it is a pulmonary vascular disorder with evidence of intrapulmonary arterial venous shunt.[4] Pulmonary dyspnea and polycythemia are common presentations of HPS. Dyspnea, cyanosis and clubbed fingers were present in most of all cases. Spider nevi is another common clinical feature of patients with HPS.

Thymosin β4 (Tβ4) is a key factor in cardiac development, growth, disease, epicardial integrity, blood vessel formation and has cardio-protective properties. However, its role in murine embryonic stem cells (mESCs) proliferation and cardiovascular differentiation remains unclear. Thus we aimed to elucidate the influence of Tβ4 on mESCs. Target genes during mESCs proliferation and differentiation were detected by real-time PCR or Western blotting, and patch clamp was applied to characterize the mESCs-derived cardiomyocytes. It was found that Tβ4 decreased mESCs proliferation in a partial dose-dependent manner and the expression of cell cycle regulatory genes c-myc, c-fos and c-jun. However, mESCs self-renewal markers Oct4 and Nanog were elevated, indicating the maintenance of self-renewal ability in these mESCs. Phosphorylation of STAT3 and Akt was inhibited by Tβ4 while the expression of RAS and phosphorylation of ERK were enhanced. No significant difference was found in BMP2/BMP4 or their downstream protein smad. Wnt3 and Wnt11 were remarkably decreased by Tβ4 with upregulation of Tcf3 and constant β-catenin. Under mESCs differentiation, Tβ4 treatment did not change the expression of cardiovascular cell markers α-MHC, PECAM, and α-SMA. Neither the electrophysiological properties of mESCs-derived cardiomyocytes nor the hormonal regulation by Iso/Cch was affected by Tβ4. In conclusion, Tβ4 suppressed mESCs proliferation by affecting the activity of STAT3, Akt, ERK and Wnt pathways. However, Tβ4 did not influence the in vitro cardiovascular differentiation.
Animals ; Cell Cycle ; drug effects ; genetics ; Cell Differentiation ; drug effects ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Extracellular Signal-Regulated MAP Kinases ; genetics ; metabolism ; Gene Expression Regulation ; drug effects ; JNK Mitogen-Activated Protein Kinases ; genetics ; metabolism ; Mice ; Mouse Embryonic Stem Cells ; cytology ; drug effects ; metabolism ; Myocytes, Cardiac ; cytology ; drug effects ; metabolism ; Nanog Homeobox Protein ; genetics ; metabolism ; Octamer Transcription Factor-3 ; genetics ; metabolism ; Patch-Clamp Techniques ; Primary Cell Culture ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Proto-Oncogene Proteins c-fos ; genetics ; metabolism ; Proto-Oncogene Proteins c-myc ; genetics ; metabolism ; STAT3 Transcription Factor ; genetics ; metabolism ; Signal Transduction ; Thymosin ; pharmacology

This article proposes a novel occupational practice model implied from the native concept of Taiji Diagram. Four elements of Taiji Diagram, namely Yang-fish, Yin-fish, Yin-fish-eye and Yang-fish-eye, are matched to the elements of occupational practice, namely person, environment, economic condition and mental condition, respectively. The interaction between persons and their environment can be thought as the interaction between Yin and Yang, and the balance would be focused on. Some different ideas may be brought from this model, such as Appropriate Challenge, Appropriate Empowerment.