Can Optical Surface Imaging Replace Non-coplanar Cone-beam Computed Tomography for Non-coplanar Set-up Verification in Single-isocentre Non-coplanar Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy for Single and Multiple Brain Metastases?

AIMS: To conduct a direct comparison regarding the non-coplanar positioning accuracy between the optical surface imaging system Catalyst HDTM and non-coplanar cone-beam computed tomography (NC-CBCT) in intracranial single-isocentre non-coplanar stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (HSRT). MATERIALS AND METHODS: Twenty patients with between one and five brain metastases who underwent single-isocentre non-coplanar volumetric modulated arc therapy (NC-VMAT) SRS or HSRT were enrolled in this study. For each non-zero couch angle, both Catalyst HDTM and NC-CBCT were used for set-up verification prior to beam delivery. The set-up error reported by Catalyst HDTM was compared with the set-up error derived from NC-CBCT, which was defined as the gold standard. Additionally, the dose delivery accuracy of each non-coplanar field after using Catalyst HDTM and NC-CBCT for set-up correction was measured with SRS MapCHECKTM. RESULTS: The median set-up error differences (absolute values) between the two positioning methods were 0.30 mm, 0.40 mm, 0.50 mm, 0.15°, 0.10° and 0.10° in the vertical, longitudinal, lateral, yaw, pitch and roll directions, respectively. The largest absolute set-up error differences regarding translation and rotation were 1.5 mm and 1.1°, which occurred in the longitudinal and yaw directions, respectively. Only 35.71% of the pairs of measurements were within the tolerance of 0.5 mm and 0.5° simultaneously. In addition, the non-coplanar field with NC-CBCT correction yielded a higher gamma passing rate than that with Catalyst HDTM correction (P < 0.05), especially for evaluation criteria of 1%/1 mm with a median increase of 12.8%. CONCLUSIONS: Catalyst HDTM may not replace NC-CBCT for non-coplanar set-up corrections in single-isocentre NC-VMAT SRS and HSRT for single and multiple brain metastases. The potential role of Catalyst HDTM in intracranial SRS/HSRT needs to be further studied in the future.

[Update points for the 2022 edition of the European Association for the Study of Liver Diseases Clinical Practice Guidelines for the Management of Hepatic Encephalopathy and comparison with China's 2018 edition guidelines].

The European Association for the Study of Liver Diseases issued the "Clinical Practice Guidelines for the Management of Hepatic Encephalopathy" in 2022, which included recommendations for clinical diagnosis, assessment, treatment, management, and prevention. The Society's "Hepatic Encephalopathy Clinical Practice Guidelines in Chronic Liver Disease," which was last published in 2014, and the "Guidelines for the Diagnosis and Treatment of Hepatic Encephalopathy in Cirrhosis," which the Chinese Society of Hepatology, Chinese Medical Association, released in 2018, have certain differences and updates in terms of comparison to terminology, grading and classification, diagnosis, clinical evaluation and treatment, management, and prevention. Herein, the updated points of this guideline and the differences between it and our nation's guidelines are summarized in order to refine and understand the guiding role of the new version of the guideline for the clinical treatment of hepatic encephalopathy and provide aid for standardizing clinical diagnosis and treatment.

Different sedation profiles with ciprofol compared to propofol represented by objective sedation level assessments by BIS and its acute hemodynamic impact in 3 escalated doses of ciprofol and propofol in healthy subjects: a single-center, open-label, randomized, 2-stage, 2-way crossover trial.

OBJECTIVE: To compare the sedation profiles and the pharmacokinetic, pharmacodynamic and safety characteristics of ciprofol and propofol at 3 escalated dose levels in healthy Chinese male subjects. PATIENTS AND METHODS: Eighteen subjects were planned to be enrolled into 3 dose groups in turn: group 1 (ciprofol-0.4 mg/kg vs. propofol-2.0 mg/kg), group 2 (ciprofol-0.6 mg/kg vs. propofol-3.0 mg/kg) and group 3 (ciprofol-0.8 mg/kg vs. propofol-4.0 mg/kg). They were randomly assigned into a ciprofol or propofol group in a ratio of 1:1, with sequences of ciprofol-propofol or propofol-ciprofol, separated with a washout period of at least 48 h. RESULTS: A total of 19 subjects were enrolled and 18 completed the trial. The median time to being fully alert after induction by ciprofol was longer than for propofol. The bispectral index (BIS) recovered significantly slower with ciprofol than with propofol 5 min and 10 min after reaching its lowest points. Systolic blood pressure (group 1: p=0.041; group 2: p=0.015; group 3: p=0.004) and mean arterial pressures (group 1: p=0.026; group 2: p=0.015; group 3: p=0.004) measured by the area under the curve below the baseline during the 2 min after induction were significantly less for ciprofol compared to propofol, but a significant change in diastolic blood pressure was only observed in group 3 (p=0.002). Eighteen (100.0%) subjects experienced 47 ciprofol-related treatment emergent adverse events (TEAEs) and 17 (94.4%) subjects had 54 propofol-related TEAEs, which were mainly hypotension, involuntary movements, respiratory depression, and pain at the injection site with severity of grade 1 or 2. CONCLUSIONS: Ciprofol may be well tolerated at higher doses in the clinical practice and exhibited significantly different sedation profiles to propofol.

Clinical Feasibility of Using Single-isocentre Non-coplanar Volumetric Modulated Arc Therapy Combined with Non-coplanar Cone Beam Computed Tomography in Hypofractionated Stereotactic Radiotherapy for Five or Fewer Multiple Intracranial Metastases.

AIMS: To evaluate the clinical feasibility of single-isocentre non-coplanar volumetric modulated arc therapy (NC-VMAT) with non-coplanar cone beam computed tomography (NC-CBCT) in hypofractionated stereotactic radiotherapy (HSRT) for five or fewer multiple brain metastases. MATERIALS AND METHODS: Ten patients with multiple brain metastases who underwent single-isocentre NC-VMAT HSRT with limited couch rotations (within ±45°) and NC-CBCT with a limited scanning range (150-200°) were included in the current analysis. Conventional single-isocentre coplanar VMAT (C-VMAT) plans were generated and compared with NC-VMAT plans. The intracranial response and toxicities of single-isocentre NC-VMAT HSRT were also evaluated. RESULTS: Compared with C-VMAT, NC-VMAT generated better target conformity (P < 0.05), a lower gradient index (P < 0.05) and better normal brain tissue sparing, especially for volume ≥12 Gy, with a median reduction of 12.65 cm3. For 45° couch rotation, NC-CBCT produced sufficient image quality to differentiate bony anatomy, even with a 150° scanning range, which could be successfully used for patient set-up correction. After NC-CBCT, 57.1% of the measured non-coplanar set-up errors exceeded the threshold value. The median gamma passing rate of NC-VMAT was higher than that of C-VMAT plans (P < 0.05). The non-coplanar beam of NC-VMAT with NC-CBCT corrections exhibited superior gamma passing rate to that without NC-CBCT corrections. The intracranial objective response rate and disease control rate for all patients were 80% (8/10) and 100% (10/10), respectively, and the most common toxicities were headache (20%) and dizziness (20%). CONCLUSION: NC-VMAT with limited couch rotation (within ±45°) combined with NC-CBCT with a limited scanning range (150-200°) markedly improves the plan quality and set-up accuracy in single-isocentre multiple-target HSRT.

[Establishment of "Chinese way" for trauma and burn management based on the engineered growth factors research and application].

Innovation and translation application are important topics that have been discussed repeatedly in national community of science and technology in recent years. We do a systemic review about the research and development history of growth factors, their application in trauma and burn management in China, and the conception and experience about the establishment of "Chinese way" for trauma and burn management in the process of constructing a disciplinary system for wound treatment with Chinese characteristics. It is our hope that these precious experiences will provide references and inspiration to our peers, especially the young generation in their research.

The effect of immunonutrition in patients with acute pancreatitis: a systematic review and meta-analysis.

BACKGROUND: The effect of immunonutrition is controversial compared to standard supplementation with respect to the management of patients with acute pancreatitis. METHODS: An online literature search on four databases (PubMed, Cochrane, Embase and Web of Science) was performed to identify all of the randomised controlled trials assessing the effects of enteral or parenteral immunonutrition in acute pancreatitis. A fixed or random effects model was chosen using revman, version 5.3 (https://revman.cochrane.org). The count data were analysed using the risk ratio (RR) and 95% confidence interval (CI). RESULTS: Five hundred and sixty-eight patients were included via our search in which 14 articles matched our criteria for enrolling the meta-analysis. Immunonutrition significantly reduced the risk of organ failure (RR = 0.42; 95% CI = 0.26-0.70, P = 0.0008), infectious complications (RR = 0.78; 95% CI = 0.62-0.99; P = 0.04) and mortality (RR = 0.37; 95% CI = 0.21-0.66; P = 0.006). Length of hospital stay was also shorter in patients who received immunonutrition (mean difference = -1.73 days; 95% CI = -2.36 to -1.10; P < 0.00001). Total interventions of patients were decreased (RR = 0.73; 95% CI = 0.55-0.97; P = 0.03). Body mass index in patients with immunonutrition was reduced more than standard nutrition (mean difference = -2.00; 95% CI = -3.96 to -0.04; P = 0.05). CONCLUSIONS: Immunonutrition support such as glutamine and ω-3 fatty acids is potentially beneficial with respect to improving clinical outcomes in patients with acute pancreatitis.

Tri-domain proteins 27 reduce inflammation and apoptosis in HK-2 cells and protect against acute kidney injury in mice.

OBJECTIVE: The kidney is one of the most commonly damaged organs in sepsis. Acute kidney injury (AKI) induced by sepsis is a clinically dangerous disease with a high mortality rate. Therefore, it is particularly important to find a way to prevent and treat sepsis-induced AKI. MATERIALS AND METHODS: Human renal tubular epithelial cell line (HK-2) and 8-week-old C57BL/6 mice were used. Lipopolysaccharide (LPS) was used to induce HK-2 cell injury and mouse AKI. Lentiviruses overexpressing TRIM27 were constructed to increase TRIM27 expression in HK-2 cells. Then, the effects of TRIM27 on the inflammation and apoptosis of HK-2 cells were analyzed, and those of TRIM27 recombinant protein on AKI in mice was detected by immunohistochemical staining and Western blot. RESULTS: It was found that TRIM27 overexpression reduced the expressions of inflammatory factors and signaling molecules in apoptosis-related pathways in HK-2 cells, but increased the ratio of Bcl-2 to Bax in HK-2 cells, indicating the anti-apoptotic effect of TRIM27. Toll-like receptor 4 (TLR4)/NF-κB signaling pathway is an important mechanism of LPS mediated renal injury, and TRIM27 overexpression in HK-2 cells significantly inhibited the activity of TLR4/NF-κB signaling pathway. In addition, AKI was significantly relieved in mice treated with TRIM27 recombinant. CONCLUSIONS: TRIM27 exerts anti-inflammatory and anti-apoptotic effects by inhibiting the TLR4/NF-κB signaling pathway, which effectively alleviates LPS-induced HK-2 cell damage and mouse AKI.

[Seizing the day and living it to the full: thirty years' independent innovation of growth factors and wound repair].

Since the discovery of fibroblast growth factor (FGF) in the early 20th century, the multiple regulatory function of FGF has been found in development, metabolic regulation and tissue regeneration. Although FGF has the potential in wound healing of clinical practice, several technical bottlenecks occurred in the development of FGF drugs. Since 1992, our team has had many technical breakthroughs and developed some class Ⅰ new drugs of FGF and medical device. At the same time, we further investigated the network of metabolic regulation and signal transduction of FGF. All the efforts were for the purpose of the development of FGF new drugs and bringing benefit to patients.

Effects of dexmedetomidine on sepsis-induced liver injury in rats.

OBJECTIVE: To explore the effect of dexmedetomidine (DEX) on sepsis-induced liver injury in rats and the mechanism of action, providing certain references for the prevention and treatment of sepsis-induced liver injury in clinical practice. MATERIALS AND METHODS: A total of 60 male Sprague Dawley (SD) rats were randomly divided into 3 groups, namely sham operation group (Sham group, n=20), sepsis-induced liver injury group [lipopolysaccharides (LPS) group, n=20], and sepsis-induced liver injury + DEX group (LPS + DEX group, n=20) using a random number table. Rat models of sepsis-induced liver injury were established by intraperitoneal injection of LPS (10 mg/kg), and at the same time, DEX was intragastrically injected at a dose of 50 µg/kg. After 24 h, the survival analysis curves of each group of rats were plotted. Meanwhile, the levels of liver function indexes and oxidative stress markers were measured at 12 h in each group of rats. Hematoxylin-eosin (H&E) staining assay was carried out to detect the morphological changes of rat liver cells in each group. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) staining assay was performed to detect the apoptosis level in rat liver tissues in each group. In addition, the expression level of Caspase 3 in three groups of rats was measured through immunohistochemical staining assay. Lastly, the effect of DEX on the protein expression of extracellular signal-regulated kinases 1/2 (ERK1/2) in liver tissues was detected via Western blotting. RESULTS: DEX significantly improved liver dysfunction induced by LPS and raised the 24 h-survival rates of rats (p<0.05). Besides, H&E staining results showed that DEX clearly relieved the pathological damage of rat liver cells caused by LPS. In comparison with LPS group, LPS + DEX group displayed more neatly arranged liver cells, less degradation and necrosis, and evidently attenuated cellular edema. Immunohistochemistry results revealed that DEX significantly reversed the increase in Caspase 3 expression resulting from LPS. The results of the TUNEL staining assay showed that DEX clearly inhibited the apoptosis of rat liver cells induced by LPS. The results of Western blotting revealed that DEX notably reversed the decrease of phosphorylated ERK1/2 (p-ERK1/2) in rat liver tissues compared with LPS group. CONCLUSIONS: DEX is able to markedly relieve LPS-induced liver injury in rats and the underlying mechanism may be related to the activation of the ERK1/2 signaling pathway.

The role novel targeted agents in the treatment of previously treated patients with advanced urothelial carcinoma (UC): a meta-analysis.

OBJECTIVE: Second-line treatment options for advanced urothelial carcinoma (UC) patients are limited. We aim to investigate the efficacy and toxicities of novel targeted agents (TAs) as salvage treatment for advanced UC by using a meta-analysis. MATERIALS AND METHODS: Relevant trials published from 1994 to 2017 were identified by an electronic search of public databases. Demographic data, treatment regimens, objective response rate (ORR), disease control rate (DCR), median progression-free and overall survival (PFS, OS) and grade 3/4 toxicities were extracted and analyzed using open Meta-Analyst software version 4.16.12 (Tufts University, URL http://tuftscaes.org/open_meta/). RESULTS: Eleven trials with 1,630 previously treated UC patients were included for analysis. The pooled ORR, DCR and 1-year OS for single targeted agent in pre-treated UC patients was 10.7% (95% CI: 10.7-19.6%), 33.2% (95% CI: 25-41.4%), and 31% (95%: 23.6-39.4%), respectively. Sub-group analysis based on specific targeted agents showed that the efficacy of immune checkpoints inhibitors (ICIs) was significantly higher than that of small molecular tyrosine-kinase inhibitors (TKIs) concerning ORR and 1-year OS. Also, a meta-analysis of three randomized controlled trials showed that the use of TAs in advanced UC patients significantly improved ORR, but not for DCR. As for grade 3 and 4 toxicities, more incidences of severe anemia, fatigue, and diarrhea were observed in the TKIs group than in ICIs group, but not for hypertension. CONCLUSIONS: Our findings support the use of immune checkpoints inhibitors, but not for tyrosine kinase inhibitors as salvage treatment for previously treated UC patients due to its potential survival benefits.

Serum hepatitis B surface antigen correlates with fibrosis and necroinflammation: A multicentre perspective in China.

The kinetics of serum hepatitis B surface antigen (HBsAg) during the natural history of hepatitis B virus (HBV) infection has been studied, but the factors affecting them remain unclear. We aimed to investigate the factors affecting HBsAg titres, using data from multicentre, large-sized clinical trials in China. The baseline data of 1795 patients in 3 multicentre trials were studied, and the patients were classified into 3 groups: hepatitis B early antigen (HBeAg)-positive chronic HBV infection (n = 588), HBeAg-positive chronic hepatitis B (n = 596), and HBeAg-negative chronic hepatitis B (n = 611). HBsAg titres in the different phases were compared, and multiple linear progression analyses were performed to investigate the implicated factors. HBsAg titres varied significantly in different phases (P = .000), with the highest (4.60 log10 IU/mL [10%-90% confidence interval: 3.52 log10 IU/mL-4.99 log10 IU/mL]) in patients with HBeAg-positive chronic HBV infection. In all phases, age and HBV DNA were correlated with serum HBsAg level. In HBeAg-positive chronic hepatitis B patients, a negative correlation between HBsAg titres and fibrosis stage was observed. Alanine amonitransferase or necroinflammatory activity was also correlated with HBsAg titres in HBeAg-negative chronic hepatitis B patients. In conclusion, decreased HBsAg titres may be associated with advancing fibrosis in HBeAg-positive chronic hepatitis B patients or increased necroinflammation in those with HBeAg-negative chronic hepatitis B. Our findings may help clinicians better understand the kinetics of HBsAg and provide useful insights into the management of this disease.

Association of LncRNA HMlincRNA717 with prognosis in pancreatic cancer.

OBJECTIVE: The aim of this study was to investigate the expression of LncRNA HMlincRNA717 in human pancreatic cancer and its correlation with clinicopathological features PATIENTS AND METHODS: Using reverse transcription quantitative polymerase chain reaction, HMlincRNA717 expression was detected in primary pancreatic cancer tissues. The correlation of HMlincRNA717 with clinicopathological features and prognosis were also analyzed. Survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. RESULTS: The expression of HMlincRNA717 was significantly decreased in pancreatic cancer tissues compared with paired adjacent normal tissues (p < 0.01). It was also proved that HMlincRNA717 expression was to be associated with clinical stage (p = 0.001), tumor size (p < 0.001), lymph node metastasis (p = 0.003), and distant metastasis (p < 0.001) in pancreatic cancer patients. Significantly shorter 5-year overall survival (OS) were observed in patients with lower expression of the HMlincRNA717 (p < 0.01). Multivariate analysis showed that decreased HMlincRNA717 expression was a poor independent prognostic factor for pancreatic cancer patients. CONCLUSIONS: Our findings showed that the expression of lncRNA HMlincRNA717 was down-regulated in pancreatic cancer and associated with overall survival, suggesting that HMlincRNA717 could be a potential prognostic biomarker for pancreatic cancer progression.

Content and distribution of different phosphorus forms in broiler chickens.

To understand the background value of phosphorus in chickens, the quantitative distribution of different phosphorus forms, including total phosphorus (TP), free phosphate (FP) and phospholipid (PL), in viscera, blood and bones of broiler chickens was investigated. Results showed that phosphorus contents exhibited significant differences in different parts of chickens. TP content of breast and thigh meat was over 5.0 g/kg, in which most of the phosphorus was in the form of water-soluble phosphates. TP content in viscera was higher than that in meat, and spleen was observed to contain the highest amount of phosphorus (10.0 g/kg). In all tested organs, FP and PL contents in liver were the highest, ranging between 1207-1989 and 81-369 mg/kg respectively. TP content in chicken bone was in the range of 52,716-136,643 mg/kg, and FP content in the bone was relatively lower than that in chicken meat.

Garlic for hypertension: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: In the past decade, garlic has become one of the most popular complementary therapies for blood pressure (BP) control used by hypertensive patients. Numerous clinical studies have focused on the BP-lowering effect of garlic, but results have been inconsistent. Overall, there is a dearth of information available to guide the clinical community on the efficacy of garlic in hypertensive patients. AIM: To systematically review the medical literature to investigate the current evidence of garlic for the treatment of hypertension. METHODS: PubMed, the Cochrane Library and EMBASE were searched for appropriate articles from their respective inceptions until August 2014. Randomized, placebo-controlled trials comparing garlic vs. a placebo in patients with hypertension were considered. Papers were independently reviewed by two reviewers and were analyzed using Cochrane software Revman 5.2. RESULTS: A total of seven randomized, placebo-controlled trials were identified. Compared with the placebo, this meta-analysis revealed a significant lowering effect of garlic on both systolic BP (WMD: -6.71 mmHg; 95% CI: -12.44 to -0.99; P = 0.02) and diastolic BP (WMD: -4.79 mmHg; 95% CI: -6.60 to -2.99; P < 0.00001). No serious adverse events were reported in any of the trials. CONCLUSION: The present review suggests that garlic is an effective and safe approach for hypertension. However, more rigorously designed randomized controlled trials focusing on primary endpoints with long-term follow-up are still warranted before garlic can be recommended to treat hypertensive patients.

5-aminolevulinic acid combined with sodium ferrous citrate ameliorates H2O2-induced cardiomyocyte hypertrophy via activation of the MAPK/Nrf2/HO-1 pathway.

Hydrogen peroxide (H2O2) causes cell damage via oxidative stress. Heme oxygenase-1 (HO-1) is an antioxidant enzyme that can protect cardiomyocytes against oxidative stress. In this study, we investigated whether the heme precursor 5-aminolevulinic acid (5-ALA) with sodium ferrous citrate (SFC) could protect cardiomyocytes from H2O2-induced hypertrophy via modulation of HO-1 expression. HL-1 cells pretreated with/without 5-ALA and SFC were exposed to H2O2 to induce a cardiomyocyte hypertrophy model. Hypertrophy was evaluated by planar morphometry, (3)H-leucine incorporation, and RT-PCR analysis of hypertrophy-related gene expressions. Reactive oxygen species (ROS) production was assessed by 5/6-chloromethyl-2',7'-ichlorodihydrofluorescein diacetate acetylester. HO-1 and nuclear factor erythroid 2-related factor 2 (Nrf2) protein expressions were analyzed by Western blot. In our experiments, HL-1 cells were transfected with Nrf2 siRNA or treated with a signal pathway inhibitor. We found several results. 1) ROS production, cell surface area, protein synthesis, and expressions of hypertrophic marker genes, including atrial natriuretic peptide, brain natriuretic peptide, atrial natriuretic factor, and ß-myosin heavy chain, were decreased in HL-1 cells pretreated with 5-ALA and SFC. 2) 5-ALA and SFC increased HO-1 expression in a dose- and time-dependent manner, associated with upregulation of Nrf2. Notably, Nrf2 siRNA dramatically reduced HO-1 expression in HL-1 cells. 3) ERK1/2, p38, and SAPK/JNK signaling pathways were activated and modulate 5-ALA- and SFC-enhanced HO-1 expression. SB203580 (p38 kinase), PD98059 (ERK), or SP600125 (JNK) inhibitors significantly reduced this effect. In conclusion, our data suggest that 5-ALA and SFC protect HL-1 cells from H2O2-induced cardiac hypertrophy via activation of the MAPK/Nrf2/HO-1 signaling pathway.

Permanent acceptance of mouse cardiac allografts with CD40 siRNA to induce regulatory myeloid cells by use of a novel polysaccharide siRNA delivery system.

The CD40/CD154 co-stimulatory pathway is crucial in alloimmune response. We developed a novel small interfering RNA (siRNA) delivery system with a poly-dA extension at the 5'-end of the siRNA sense strand that was stably incorporated into 1,3-ß-glucan (schizophyllan, SPG). This was captured and incorporated into dendritic cells (DCs) through its receptor, Dectin-1, specifically silencing CD40 genes (siCD40) to exert immunoregulatory activity. siCD40/SPG-treated CBA mice permanently accepted B10 fully mismatched cardiac allografts. Consistent with graft survival, the infiltration of CD4(+), CD8(+) T cells into the graft was lower, and that the numbers of CD40(low)CD11c(+) DCs cells and CD4(+)Foxp3(+)cells were increased in both the graft and in the recipient spleen. In addition, naive CBA recipients given an adoptive transfer of splenocytes from the primary recipients with siCD40/SPG accepted a heart graft from donor-type B10, but not third-party Balb/c mice. In conclusion, the treatment with siCD40/SPG targeting DCs could generate antigen-specific Tregs, resulting in the permanent acceptance of mouse cardiac allografts. These findings have important implications for clarifying the mechanism underlying the induction of tolerance in DCs, and also highlight the potential of immunomodulation and the feasibility of siRNA-based clinical therapy in the transplantation field.

Influence of sirolimus-induced TGF-ß secretion on mouse Treg cell proliferation.

We examined the effects of co-culturing CD4+ CD25+ Treg cells with sirolimus or cyclosporin A on Treg cell proliferation and differentiation and on transforming growth factor-ß (TGF-ß) and Foxp3 expression. CD4+ CD25+ Treg cells were harvested from mononuclear cells of spleens of C57BL/6 mice using immunomagnetic beads and divided into control, sirolimus, and cyclosporine groups. Following a 96-h co-culture, Treg cells were assayed by flow cytometry. FoxP3 and TGF-ß mRNA levels and secretion were assayed by reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Smad protein of the TGF-ß signaling pathway was assayed by western blot and its effect on CD4+ CD25+ FoxP3+ Treg cell proliferation was determined. Sirolimus-promoted differentiation and proliferation was examined using a TGF-ß neutralizing antibody. Sirolimus-treated CD4+ T cell TGF-ß secretion increased 2.5X over control levels (P < 0.01), but that of the cyclosporine group decreased marginally (P > 0.05). The CD4+ cell proportion decreased significantly (41.25 vs 69.22%, P < 0.01) and slightly (65.21 vs 69.22, P > 0.05) in the cyclosporine and sirolimus groups, respectively. T cell Foxp3 mRNA expression was significantly higher in the sirolimus-treated than in the cyclosporine (53.7 vs 40.2%, P < 0.05) and control groups (P < 0.01), but was significantly lower in the cyclosporine group than in controls (23.6 vs 40.2%, P < 0.01). Overall, sirolimus promoted CD4+ CD25+ Treg cell proliferation and growth in vitro, whereas cyclosporin A inhibited proliferation. Sirolimus might promote CD4+ CD25+ FoxP3+ regulatory T cell proliferation by inducing TGF-ß secretion in vivo.

The PI3K/Akt signal hyperactivates Eya1 via the SUMOylation pathway.

Eyes absent 1 (Eya1) is a conserved critical regulator of organ-specific stem cells. Ectopic Eya1 activities, however, promote transformation of mammary epithelial cells. Signals that instigate Eya1 oncogenic activities remain to be determined. Here, we show that Akt1 kinase physically interacts with Eya1 and phosphorylates a conserved consensus site of the Akt kinase. PI3K/Akt signaling enhances Eya1 transcription activity, which largely attributes to the phosphorylation-induced reduction of Eya1 SUMOylation. Indeed, SUMOylation inhibits Eya1 transcription activity; and pharmacologic and genetic activation of PI3K/Akt robustly reduces Eya1 SUMOylation. Wild-type but not Akt phosphorylation site mutant Eya1 variant rescues the cell migratory phenotype of EYA1-silenced breast cancer cells, highlighting the importance of Eya1 phosphorylation. Furthermore, knockdown EYA1 sensitizes breast cancer cells to the PI3K/Akt1 inhibitor and irradiation treatments. Thus, the PI3K/Akt signal pathway activates Eya1. These findings further suggest that regulation of SUMOylation by PI3K/Akt signaling is likely an important aspect of tumorigenesis.

Recombinant VP1 protein of duck hepatitis virus 1 expressed in Pichia pastoris and its immunogenicity in ducks.

The VP1 gene of duck hepatitis virus type 1 (DHV-1) strain VJ09 was amplified by reverse transcription PCR from the liver of a duckling with clinical symptoms of viral hepatitis. The resulting VP1 cDNA was 720 bp in length and encoded a 240-amino-acid protein. In VP1 gene-based phylogenetic analysis, the VJ09 strain grouped with DHV-1 genotype C. The VP1 gene was inserted into the expression vector pPICZαA and expressed in Pichia pastoris. The expressed VP1 protein was purified and identified by western blot analysis. To evaluate the recombinant VP1's immunogenic potential in ducklings, the antibodies raised in the immunized ducklings were titrated by ELISA, and lymphocyte proliferation and virus neutralization assays were performed. The results show that the recombinant VP1 protein induced a significant immune response in ducklings and this could be a candidate for the development of a subunit vaccine against DHV-1 genotype C.

Ginkgo biloba extract for essential hypertension: a systemic review.

BACKGROUND: Ginkgo biloba extract (GBE), a traditional natural herbal product, is often used in the treatment of essential hypertension (EH) as complementary therapy in China and European countries. AIM: To critically assess the current clinical evidence of efficacy and safety of GBE for EH. METHODS: 7 electronic databases (Cochrane Library, PubMed, EMBASE, VIP, CBM, Wanfang data, and CNKI) were searched to identify randomized controlled trials (RCTs) of GBE for EH. Methodological quality was assessed independently using the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: A total of 9 RCTs with 1012 hypertensive patients were identified and reviewed. Most RCTs were of high risk of bias with flawed study design and poor methodological quality. 6 trials demonstrated potential positive effect of GBE as complementary therapy on BP reduction when compared with antihypertensive drug therapy; however, it was not associated with a statistically significant effect on both SBP and DBP reduction in 3 other trials. Despite the positive findings, there were so many methodological limitations and significant clinical heterogeneity. Most of the trials did not report adverse effects, and the safety of GBE is still uncertain. CONCLUSION: No confirmative conclusions on the efficacy and safety of GBE for EH could be drawn. More rigorous trials are warranted to support their clinical use.