Risk factors of negative diagnosis of MRCP in acute biliary pancreatitis patients with choledocholithiasis.

BACKGROUND: Assessment of the presence of choledocholithiasis is crucial among acute biliary pancreatitis (ABP). Magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasonography (EUS) are widely used to identify the gallstones of common bile duct (CBD). EUS provides better diagnostic accuracy and sensitivity than MRCP but carries a certain risk due to sedation. We investigated the risk factors of negative diagnosis of MRCP in ABP patients with choledocholithiasis for better selection of MRCP or EUS. METHODS: A total of 2321 ABP patients were retrospectively included in this study. Based on the exclusion criteria, 337 ABP patients with negative MRCP results were ultimately included. Among these patients, 75 patients had positive EUS findings. Univariate and multivariate logistic regression models were used to screen the risk factors of negative diagnosis of MRCP in ABP patients with choledocholithiasis. RESULTS: Patients with positive EUS findings were older (62.0 vs. 55.0) and had higher rate of cholecystectomy history (18.7% vs. 7.3%) than those with negative EUS findings. The result of univariate logistic regression showed that the history of cholecystectomy, age and sex were potential risk factors (all p < 0.05). Then after adjusting the other potential risk factors (Direct bilirubin (DBIL), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP)), a history of cholecystectomy (OR = 2.859 [1.312,6.23]), older age (1.03 [1.009,1.052]) and male (2.016 [1.152,3.528]) were independent risk factors of negative diagnosis of MRCP in ABP patients with choledocholithiasis. CONCLUSIONS: The history of cholecystectomy, older age and male are independently associated with an increased risk of negative diagnosis of MRCP in ABP patients with choledocholithiasis. We suggest that patients with these risk factors should undergo EUS first, rather than MRCP.

The mechanism of internal and external efficacy influences residents' pro-environmental behavior through environmental willingness.

The Chinese government's environmental conservation efforts require the active participation of all society. This study investigated how internal and external efficacy influence pro-environmental behavior with environmental willingness as a mediator. This study employed a structural equation model to analyze the data from 1499 survey questionnaires. The analysis revealed that both internal and external efficacy can enhance individuals' pro-environmental behavior in the private and public spheres. External efficacy has a stronger impact on environmental willingness and public sphere environmental behavior, while internal efficacy more significantly influences private sphere environmental behavior. Additionally, environmental willingness only mediates efficacy and public sphere environmental behavior. The innovation of this study is the examination of internal and external efficacy from the perspective of different sources and the comparison of their differential impacts on pro-environmental behavior. Relevant policies should effectively enhance residents' internal and external efficacy to comprehensively improve their level of pro-environmental behavior.

Serum CTRP9 and high-molecular weight adiponectin are associated with ischemic stroke.

BACKGROUND: C1q/TNF-related protein 9 (CTRP9) and adiponectin (APN) have beneficial metabolic regulatory and vasoprotective effects. This study explored alteration of CTRP9 and APN multimers during onset of ischemic stroke and development, to provide novel clinical and experimental basis for recognition and prevention of ischemic stroke. METHODS: There were 269 patients with ischemic stroke and 182 control subjects included in this study. Serum levels of CTRP9 and APN multimers in different disease stages were measured. RESULTS: Serum CTRP9, total APN (tAPN), and high-molecular weight (HMW) APN decreased gradually in stage I (acute stage, within 72 h of onset) of ischemic stroke and increased during stage III (11th day to one month) and stage IV (1 month after), compared to control. In the non-hyperlipidemia group, serum CTRP9, tAPN, and HMW were decreased in ischemic stroke patients compared to control (P < 0.05). Serum CTRP9 is closely related to serum tAPN and HMW (r = 0.992, 0.991). Serum CTRP9 are protective against ischemic stroke (OR = 0.400, 95% CI 0.197-0.810, P < 0.05). CONCLUSIONS: Lower serum CTRP9, tAPN, LMW, and HMW are significantly associated with increased ischemic stroke risk in non-hyperlipidemia subjects. CTRP9, tAPN, and HMW isoforms may be valuable clinical indicators for patients with ischemic stroke.

Vocal acoustic features may be objective biomarkers of negative symptoms in schizophrenia: A cross-sectional study.

BACKGROUND: There are currently no objective biomarkers that allow the quantification of negative symptoms of schizophrenia. This study therefore explored the use of acoustic features in identifying the severity of negative symptoms in patients with schizophrenia. METHODS: We recruited 79 inpatients who were diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (the schizophrenia group) at the Huilongguan Hospital in Beijing, China, and 79 healthy controls from the surrounding community (the control group). We assessed the clinical symptoms of the patients with schizophrenia using the Positive and Negative Syndrome Scale (PANSS) and the Brief Negative Symptom Scale (BNSS) and recorded the voice of each participant as they read emotionally positive, neutral, and negative texts. The Praat software was used to analyse and extract acoustic characteristics from the recordings, such as jitter, shimmer, and pitch. The acoustic differences between the two groups of participants and the relationship between acoustic characteristics and clinical symptoms in the patient group were analysed. RESULTS: There were significant differences between the schizophrenia and control groups in pitch, voice breaks, jitter, shimmer, and the mean harmonics-to-noise ratio (p < 0.05). Jitter was negatively correlated with the blunted affect and alogia subscale scores of the BNSS, both in the positive and neutral emotion conditions, but the correlation disappeared in the negative emotion condition. However, shimmer exhibited a stable negative correlation with the blunted affect and alogia subscale scores of the BNSS in all three emotion conditions. A linear regression analysis showed that pitch, jitter, shimmer, and age were statistically significant predictors of BNSS subscale scores. CONCLUSIONS: Acoustic emotional expression differs between patients with schizophrenia and healthy controls. Some acoustic characteristics are related to the severity of negative symptoms, regardless of semantic emotions, and may therefore be objective biomarkers of negative symptoms. A systematic method for assessing vocal acoustic characteristics could provide an accurate and feasible means of assessing negative symptoms in schizophrenia. TWEET: Acoustic emotional expression differs between patients with schizophrenia and healthy controls. A systematic method for assessing vocal acoustics could provide an accurate and feasible means of assessing negative symptoms in schizophrenia.

Genetic Diversity, Antibiotic Resistance, and Pathogenicity of Aeromonas Species from Food Products in Shanghai, China.

Objective: Aeromonas has recently been recognized as an emerging human pathogen. Aeromonas-associated diarrhea is a phenomenon occurring worldwide. This study was designed to determine the prevalence, genetic diversity, antibiotic resistance, and pathogenicity of Aeromonas strains isolated from food products in Shanghai. Methods: Aeromonas isolates ( n = 79) collected from food samples were analyzed using concatenated gyrB- cpn60 sequencing. The antibiotic resistance of these isolates was determined using antimicrobial susceptibility testing. Pathogenicity was assessed using ß-hemolytic, extracellular protease, virulence gene detection, C. elegans liquid toxicity (LT), and cytotoxicity assays. Results: Eight different species were identified among the 79 isolates. The most prevalent Aeromonas species were A. veronii [62 (78.5%)], A. caviae [6 (7.6%)], A. dhakensis [3 (3.8%)], and A. salmonicida [3 (3.8%)]. The Aeromonas isolates were divided into 73 sequence types (STs), of which 65 were novel. The isolates were hemolytic (45.6%) and protease-positive (81.0%). The most prevalent virulence genes were act (73.4%), fla (69.6%), aexT (36.7%), and ascV (30.4%). The results of C. elegans LT and cytotoxicity assays revealed that A. dhakensis and A. hydrophila were more virulent than A. veronii, A. caviae, and A. bivalvium. Antibiotic resistance genes [ tetE, blaTEM, tetA, qnrS, aac(6)-Ib, mcr -1, and mcr-3] were detected in the isolates. The multidrug-resistance rate of the Aeromonas isolates was 11.4%, and 93.7% of the Aeromonas isolates were resistant to cefazolin. Conclusion: The taxonomy, antibiotic resistance, and pathogenicity of different Aeromonas species varied. The Aeromonas isolates A. dhakensis and A. hydrophila were highly pathogenic, indicating that food-derived Aeromonas isolates are potential risks for public health and food safety. The monitoring of food quality and safety will result in better prevention and treatment strategies to control diarrhea illnesses in China.

[Analysis of Gene Mutation Characteristics and Prognosis of Elderly Patients with Acute Myeloid Leukemia].

OBJECTIVE: To investigate the characteristics of gene mutation in elderly patients with acute myeloid leukemia (AML) and its effect on prognosis. METHODS: The clinical and laboratorial characteristics of 54 AML patients (≥60 years old) in Department of Hematology, Tangdu Hospital were analyzed retrospectively during April 2016 to October 2019. Thirty-four AML/myelodysplastic syndrome/myeloproliferative neoplasm related mutant genes were detected by second-generation sequencing technology, and their clinical characteristics, treatment effect, and influence on prognosis were analyzed. RESULTS: All the patients received DAC+CAG induction treatment, after 1-2 couses of treatment, 36 cases (66.7%) achieved complete response, with a total effective rate of 75.9%, and the median survival time was 17 months. The most frequent mutant genes were TET2 (33.3%), CEBPA (31.5%), DNMT3A (18.5%), ASXL1 (16.7%), NRAS (14.8%), RUNX1 (14.8%), FLT3-ITD (12.9%), TP53 (12.9%), NPM1 (12.9%), and IDH2 (12.9%). Among 7 patients with TP53 mutation, 6 cases obtained complete response after 1-2 courses of induction treatment, but there was no statistically significant difference in the effect on prognosis. Patients with FLT3-ITD and NRAS mutations had shorter overall survival time compared with who had no mutation (P=0.47, P=0.48). Multivariate analysis showed that FLT3-ITD and NRAS mutations were poor prognostic factors. CONCLUSION: The incidence of TET2 gene mutation is high in elderly AML patients. AML patients with TET2 and TP53 mutations may benefit from Decitabine-based chemotherapy. However, patients with FLT3-ITD and NRAS mutations have a short survival time, and may have a poor prognosis.

Hyperlipidemic plasma molecules bind and inhibit adiponectin activity.

INTRODUCTION: Adiponectin is a potent vascular protective molecule. Recent findings have suggested adiponectin resistance during early diabetes. However, the molecular mechanisms responsible remain unidentified. Here, we took an unbiased approach to identify whether hyperlipidemic plasma molecules exist that bind and inhibit adiponectin function, contributing to adiponectin resistance and diabetic vascular injury. METHODS: Adult rats were randomly assigned to receive either a normal or a high-fat diet for 8 weeks. Plasma was co-immunoprecipitated with anti-APN antibody and analyzed by mass spectrometry. The APN binding molecules and their effect upon APN biological activity were determined. RESULTS: As expected, the high-fat-diet increased plasma triglyceride, total cholesterol, and low-density lipoprotein. Importantly, the circulating APN level was significantly increased at this time point. Mass spectrometry identified 18 proteins with increased APN binding in hyperlipidemic plasma, among which four proteins critical in lipid metabolism, including apolipoprotein A1 (APOA1), APOA4, APOC1, and paraoxonase 1, were further investigated. Incubating recombinant APN with APOA1 markedly (P < 0.01), and incubating with APOC1 significantly (P < 0.05), inhibited APN activity as evidenced by the reduced AMPK activation in HUVECs. APOA4 and paraoxonase 1 incubation had no effect upon APN activity. Finally, plasma APOA1 was significantly increased (P < 0.05) in hyperlipidemic plasma compared with the control plasma. CONCLUSIONS: It was demonstrated for the first time that increased APOA1 and APOC1 in hyperlipidemic plasma binds and inhibits APN activity. This result not only identifies a novel molecular mechanism responsible for adiponectin resistance during early stage diabetes, but also provides additional new insight into the diverse/controversial (protective and harmful) functions of high-density lipoprotein.

[Clinical Characteristics and Prognosis of Acute Myeloid Leukemia Patients with ASXL1 Gene Mutation].

OBJECTIVE: To investigate the clinical characteristics and prognosis of acute myeloid leukemia(AML) patients with ASXL1 mutation. METHODS: The clinical data of 229 newly diagnosed AML patients treated in our hospital from April 2016 to October 2019 were analyzed retrospectively. The next-generation sequencing technology was used to detect gene mutations in all the patients, the clinical characteristics of the patients with ASXL1 mutation were analyzed. RESULTS: ASXL1 gene mutation was detected out in 45 patients(19.6%). Among these patients, the frameshift mutation (n=22,48.9%) was most common, followed by missense mutation (n=15, 33.3%) and nonsense mutation (n=8,17.8%), respectively, all of them were located at exon 12. The median mutation rate was 32.47%(range, 2.74%-53.50%). The median age of the patients with ASXL1 mutation was 54(range, 14-74) years old, and most of the patients were male, and most of them with the history of MDS or MPN, and low white blood cell count at the initial diagnosed (P<0.05). Patients with ASXL1 mutation showed a lower CR rate than that of without ASXL1 mutation. Patients with or without ASXL1 mutation showed a statistically significant difference in survival at 20 months (P=0.042), while there was no significant difference between the patients in the two groups over 20 months (P=0.505). All the 6 patients with ASXL1 mutation in low-risk group were survived, while the median OS time was 16 months in the high-risk group(P=0.034). Multivariate analysis showed that the history of MDS or MPN and CR rate from induction therapy were the independent risk factors affecting survival of the patients. CONCLUSION: Frameshift mutation is commonly in AML patients with ASXL1 gene mutation, and ASXL1 mutation were more often in men, the history of MDS or MPN, and low white blood cell count. The CR rate of the patients with ASXL1 mutation was lower than that of the AML patients without ASXL1 mutations, AML patients with ASXL1 mutation showed poor short-term efficacy, but there was no significant difference between the two groups in long-term survival over 20 months.

[Aerosol salt damage is the main problem of landscaping in the coastal areas of southern China]. / 盐雾危害是南方滨海地区园林绿化的主要困难.

Both the growth and survival of landscape plants are difficult due to the harsh natural conditions in coastal areas of southern China. Many plants suffer from symptoms of salt damage. Different from the damages by salt in the soil, the symptoms of windblown salt are damage to young shoots and leaves. Plants at the windward side are damaged more than the leeward side. These cha-racteristics imply that the damage is due to salt in aerosols instead of salt in the soil. To test this hypothesis, we measured plant growth, soil and climate factors in 24 frontline coastal counties and cities of China. The results showed that the first-line coastal plants showed strong symptoms of salt damage, especially in the Taiwan Strait area (85.4% belonged to desalinized soil), and that the damage level was highly correlated with wind speed. Our results confirmed that aerosol salt is the major cause of plant damage in the coastal areas of southern China. We constructed the first distribution map of salt damage along frontline coastal regions of southern China and proposed methods for diagnosing aerosol salt damage. Selecting and configuring aerosol salt-tolerant plants, greening engineering measures, and follow-up maintenance were suggested for improving the overall effect and level of landscaping in the coastal areas of southern China.

Dynamic changes in the systemic immune responses of spinal cord injury model mice.

Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury. This study aimed to decipher the dynamics of systemic immune responses, initiated by spinal cord injury. The spinal cord in mice was completely transected at T8. Changes in the in vivo inflammatory response, between the acute and subacute stages, were observed. A rapid decrease in C-reactive protein levels, circulating leukocytes and lymphocytes, spleen-derived CD4+ interferon-γ+ T-helper cells, and inflammatory cytokines, and a marked increase in neutrophils, monocytes, and CD4+CD25+FOXP3+ regulatory T-cells were observed during the acute phase. These systemic immune alterations were gradually restored to basal levels during the sub-acute phase. During the acute phase of spinal cord injury, systemic immune cells and factors showed significant inhibition; however, this inhibition was transient, and the indicators of these serious disorders gradually returned to baseline levels during the subacute phase. All experiments were performed in accordance with the institutional animal care guidelines, approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum Tower Hospital, China (approval No. 2019AE01040) on June 25, 2019.

Anti-HSV-1 effect of dihydromyricetin from Ampelopsis grossedentata via the TLR9-dependent anti-inflammatory pathway.

OBJECTIVES: Herpes simplex virus 1 (HSV-1) is one of the most prevalent viruses in humans worldwide. Owing to limited therapeutic options mainly with acyclovir (ACV) and analogues and the emergence of ACV-resistant strains, new drugs with different modes of action and low toxicity are required. The aim of this study was to determine the anti-HSV-1 effect and mechanism of action of the flavonoid compound dihydromyricetin (DHM) from Ampelopsis grossedentata. METHODS: The HSV-1 inhibitory effect of DHM was evaluated by measuring plaque formation and generation of progeny virus as well as expression of HSV-1-related genes in Vero cells. The molecular mechanism of the antiviral activity of DHM against HSV-1 was explored by real-time quantitative PCR and ELISA. RESULTS: DHM presented a significant inhibitory effect on HSV-1 plaque formation and generation of progeny virus, with an EC50 (50% effective concentration) of 12.56 µM in Vero cells. Furthermore, expression of HSV-1 immediate-early genes (ICP4 and ICP22), early genes (ICP8 and UL42) and late genes (gB, VP1/2) was decreased by DHM at concentrations of 16 µM and 32 µM. DHM specifically suppressed mRNA levels of Toll-like receptor 9 (TLR9), leading to inhibition of the inflammatory transcriptional factor NFκB and a decrease in TNFα. CONCLUSION: These findings indicate that the effective inhibitory activity of DHM was achieved by suppressing TNFα production in a TLR9-dependent manner. Although further studies are needed to better characterise the activity of DHM in vivo, the results suggest this extract as a promising new anti-HSV-1 agent.

Prognostic value of preoperative hematological markers combined with molecular pathology in patients with diffuse gliomas.

The prediction of clinical outcome for patients with infiltrative gliomas is challenging. Although preoperative hematological markers have been proposed as predictors of survival in glioma and other cancers, systematic investigations that combine these data with other relevant clinical variables are needed to improve prognostic accuracy and patient outcomes. We investigated the prognostic value of preoperative hematological markers, alone and in combination with molecular pathology, for the survival of 592 patients with Grade II-IV diffuse gliomas. On univariate analysis, increased neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), and decreased albumin-to-globulin ratio (AGR), all predicted poor prognosis in Grade II/III gliomas. Multivariate analysis incorporating tumor status based on the presence of IDH mutations, TERT promoter mutations, and 1p/19q codeletion showed that in lower-grade gliomas, high NLR predicted poorer survival for the triple-negative, IDH mutation only, TERT mutation only, and IDH and TERT mutation groups. NLR was an independent prognostic factor in Grade IV glioma. We therefore propose a prognostic model for diffuse gliomas based on the presence of IDH and TERT promoter mutations, 1p/19q codeletion, and NLR. This model classifies lower-grade gliomas into nine subgroups that can be combined into four main risk groups based on survival projections.

Metformin improved oxidized low-density lipoprotein-impaired mitochondrial function and increased glucose uptake involving Akt-AS160 pathway in raw264.7 macrophages.

BACKGROUND: Macrophage accumulation in the vascular wall is a hallmark of atherosclerosis. Studies showed that shifting of oxidized lipids-induced inflammatory macrophages towards an anti-inflammatory phenotype by promoting oxidative metabolism attenuated atherosclerosis progression. Therefore, this study aimed to investigate whether metformin, which has ameliorated atherosclerosis in animal models and clinical trials, modulated oxidized low-density lipoprotein (Ox-LDL) induced inflammatory status in macrophages by regulating cellular oxidative metabolism. METHODS: Murine raw264.7 macrophages were incubated with Ox-LDL (50 µg/mL) in the presence or absence of metformin (15 µmol/L) for 24 h. Real-time polymerase chain reaction was used to quantify the transcription of classically activated (M1) pro-inflammatory and alternatively activated (M2) anti-inflammatory markers and mitochondrial DNA copy numbers. Cellular reactive oxygen species (ROS) production and mitochondrial membrane potential were detected by immunofluorescence. Cellular adenosine triphosphate (ATP) synthesis, glucose uptake, and lactic acid production were measured by commercial kit and normalized to cellular lysates. Western blotting analysis was performed to detect the expression of mitochondrial fusion/fission related proteins, enzymes mediating lipid metabolism and signaling pathway of glucose transport. Differences between groups were analyzed using one-way analysis of variance. RESULTS: Metformin improved Ox-LDL-impaired anti-inflammatory phenotype in raw264.7 macrophages as shown by up-regulated transcription of anti-inflammatory markers including interleukin 10 (0.76 ±â€Š0.04 vs. 0.94 ±â€Š0.01, P = 0.003) and Resistin-like molecule alpha (0.67 ±â€Š0.08 vs. 1.78 ±â€Š0.34, P = 0.030). Conversely, Ox-LDL-diminished phosphorylation of Akt was up-regulated by metformin treatment (0.47 ±â€Š0.05 vs. 1.02 ±â€Š0.08, P = 0.040), associated with an improvement of mitochondrial function, characterized by decreased ROS generation (2.50 ±â€Š0.07 vs. 2.15 ±â€Š0.04, P = 0.040), increased lipid oxidation, and elevated cellular ATP production (0.026 ±â€Š0.001 vs. 0.035 ±â€Š0.003, P = 0.020). Moreover, metformin-mediated Akt activation increased Akt substrate of 160 kDa (AS160) phosphorylation (0.51 ±â€Š0.04 vs. 1.03 ±â€Š0.03, P = 0.0041), promoted membrane translocation of glucose transporter 1, and increased glucose influx into the cells (4.78 ±â€Š0.04 vs. 5.47 ±â€Š0.01, P < 0.001). CONCLUSION: This study suggested that targeting macrophage metabolism with new or existing drugs had therapeutic potential for the prevention and treatment of diabetes-accelerated atherosclerosis.

Cerebral functional abnormalities in patients with nasopharyngeal carcinoma after radiotherapy: an observational magnetic resonance resting-state study.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is sensitive to radiotherapy (RT). However, neurocognitive complications such as memory loss and learning and attention deficits emerge in the survivors of NPC who received RT. It remains unclear how radiation affects patient brain function. This pilot study aimed at finding cerebral functional alterations in NPC patients who have received RT. METHODS: From September 2014 to December 2016, 42 individuals, including 22 NPC patients and 20 normal volunteer controls in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, were recruited in this study. All patients received resting-state functional magnetic resonance imaging scans and neurocognitive tests 1 day before the initiation of RT (baseline) and 1 day after the completion of RT; the 20 normal controls were also subjected to the same scans and tests. The amplitude of the low-frequency fluctuations (ALFF) in blood oxygen level-dependent signals and functional connectivity (FC) were used to characterize cerebral functional changes. Independent t test, paired t test, and analysis of variances were used to obtain statistical significance across groups. RESULTS: After RT, NPC patients showed significantly decreased ALFF values in the calcarine sulcus, lingual gyrus, cuneus, and superior occipital gyrus and showed significantly reduced FC mainly in the default mode network (P < 0.05, corrected by AlphaSim). Relative to the controls, ALFF was decreased in the lingual gyrus, calcarine sulcus, cingulate cortex, medial prefrontal gyrus (P < 0.05, corrected by AlphaSim), and FC reduction was found in multiple cerebellar-cerebral regions, including the cerebellum, parahippocampus, hippocampus, fusiform gyrus, inferior frontal gyrus, inferior occipital gyrus, precuneus, and cingulate cortex (P < 0.001, corrected by AlphaSim). CONCLUSIONS: Cerebral functional alterations occur immediately after RT. This study may provide an explanation for the cognitive deficits in the morphologically normal-appearing brains of NPC patients after RT and may contribute to the understanding of the complex mechanism of RT.

Uptake and Transport Mechanism of Dihydromyricetin Across Human Intestinal Caco-2 Cells.

A variety of beneficial pharmacological activities have been reported for dihydromyricetin (DMY), however, its oral bioavailability is poor and the intestinal absorption profiles of DMY remains unknown. The aim of this study was to investigate the uptake and transport mechanism of DMY in human intestinal Caco-2 cells. DMY was detected using a liquid chromatography-tandem mass spectrometry method. Several factors including time, concentration, pH, temperature and efflux transporters were systematically evaluated. DMY was poorly absorbed by a passive diffusion mechanism. The uptake and transport of DMY were time and concentration dependent. Interestingly, decreasing the pH from 8.0 to 6.0 markedly enhanced the DMY uptake, but didn't significantly affect its bidirectional transport. Efflux transporters, multidrug resistance protein 2 and breast cancer resistance protein also influenced the DMY uptake and transport processes. This work details the uptake and transport characteristics of DMY and provides basis for future study. PRACTICAL APPLICATION: This study elucidated the uptake and transport characteristics of dihydromyricetin (DMY). DMY was poorly absorbed by a passive diffusion mechanism. The uptake and transport of DMY were time and concentration dependent. Interestingly, pH affected DMY uptake but not its bidirectional transport. MRP2 and BCRP were involved in the uptake and transport of DMY, which hindered the absorption of DMY in the intestinal. Thus, the present study may provide useful information for designing DMY delivery systems and avoiding DMY-drug interactions.

[Clinical Efficacy of Decitabine-Based Chemotherapy Regimens in the Treatment of Newly Diagnosed Elderly Patients with Acute Myeloid Leukemia].

OBJECTIVE: To investigate the safety and efficacy of decitabine combined with CAG regimen in the treat-ment of newly diagnosed elderly patients with acute myeloid leukemia(AML). METHODS: Fourty-nine patients with newly diagnosed acute myeloid leukemia (except M3) who were admitted to our hospital were selected. All the patients were older than 50 years old, and allogeneic hematopoietic stem cell transplantation could not be performed for various reasons. Decitabine-based chemotherapy regimens were used during induction therapy including single decitabine therapy(DAC), decitabine combined with CAG regimen(DAC-CAG) and decitabine combined with HAAG regimen(DAC-HAAG). Most of patients continued to use the original treatment after complete remission, while others were given the standard "3+7" regimen chemotherapy. A total of 2-4 courses of treatment was conducted in the majority of patients. RESULTS: All of the 49 patients completed the induction therapy, in which 26 cases achieved complete remission(CR), 7 cases achieved partial remission(PR) and no response(NR) existed in 16 cases. The complete remission and the overall response rate(ORR) were 53% and 67% respectively. The overall response rate of DAC group, DAC-CAG group and DAC-HAAG group were 17%, 77% and 63% respectively. 14 patients were infected and 1 patients died of pulmonary infection during the induction therapy. The median number of suspended red blood cells and platelet infused were 9 units and 69 units respectively. Neutrophil recovery time was 15.1 days while the platelet recovery time was 20.1 days during the induction therapy. The mean follow-up time was 21 months. Overall survival(OS) was 75% at 6 months, 30% at 1 year, and 26% at 2 year, while disease-free survival(DFS) was 83% at 3 months, 54% at 1 year, and 47% at 2 year. The induction therapy could reach CR that was an independent prognostic factor, however, the initial white blood cell count, platelet count, age, chemotherapy regimen, prognostic stratification and whether complical by pnenmonia during chemotherapy were not independent prognostic factors. CONCLUSION: The induction efficacy of decitabine combined with chemotherapy is superior to that of decitabine alone. The outcome of induction chemotherapy is an independent prognostic factor, however, the high white blood cell count, poor karyotype, complications and AML with myelodysplasia-related changes do not affect long-term survival. DAC-CAG regimen is effective and have relatively few adverse reactions in AML. It is suitable for the patients who are ineligible for conventional chemotherapy.

Approaches to developing fast release pellets via wet extrusion-spheronization.

Microcrystalline cellulose (MCC) is widely regarded as the excellent choice to manufacture pellets via wet extrusion-spheronisation (ES) process due to its excellent water uptake capability, water holding capacity, desirable rheological properties, cohesiveness and plasticity etc. Nevertheless, in spite of all these advantages, limitations associated with the application of MCC also have been reported. The most prevailing limitation is prolonged or incomplete drug release profile due to the lack of disintegration as pellet contracts significantly during the drying process, especially when in combination with poorly soluble drug at a high level. This characteristic limits the application of MCC in immediate release formulations. Over the years, many approaches have been tried to overcome this disadvantage, such as modifying MCC, incorporation of superdisintegrant, increasing the porosity of pellet, partial or complete substitution for MCC, enhancing the solubility of poorly soluble drug (e.g. solid dispersion, self-emulsifying drug-delivery system), etc. In this review, we will provide an updated and integrated discussion of current approaches to prepare fast release pellets via wet ES.

Gastrointestinal stability of dihydromyricetin, myricetin, and myricitrin: an in vitro investigation.

The gastrointestinal (GI) stability of three flavonoids, dihydromyricetin (DMY), myricetin (MYR), and myricitrin (MYT), was examined in simulated physiological fluids. Several factors that may influence the degradation rate of theses flavonoids were evaluated, including pH and the presence of pepsin and pancreatin enzymes. We found that GI stability followed the order of MYT > DMY > MYR. These flavonoids were stable in simulated gastric fluids and buffer solutions (pH 1.2), but encountered a pseudo-first-order kinetic degradation in simulated intestinal fluids and buffer solutions (pH 6.8). We conclude that it is the pH, rather than the presence of pepsin or pancreatin, which most strongly influences the stability of these three flavonoids. Further study of the stability of the compounds using a pH range (1.0-8.0) indicated potential instability in the duodenum, small intestine, and colon. Therefore, we conclude that the low bioavailability of these flavonoids may be due to their poor stability in the GI tract.

Shear Stress-sensitive Carriers for Localized Drug Delivery.

Stenosis of the critical blood vessels, which occurs in a variety of cardiovascular and cerebrovascular diseases, is one of leading causes of death in the world. Vascular stenosis will significantly alter the hemodynamic features in the vessel. Hemodynamic shear stress, one of the most important physical parameters of blood flow, will be dramatically elevated at the stenotic site. When platelets flow through the constricted site, they will sense these abnormally high shear stresses, and then respond by activating, sticking to the vascular wall, and aggregating at these sites. The shear-dependent platelet activation inspired a novel targeting platform-shear stress activated drug targeting delivery. The shear-activated drug delivery systems preferentially release their content under elevated shear stress, providing a novel approach to cure various diseases, in particular, cardiovascular diseases. In this review, we, on one hand, introduced the features of hemodynamic shear stress under both physiological and pathological conditions. On the other hand, we summarized the carriers displaying sensitivity to shear stress, such as liposomes, aggregations, gels, emulsions, in addition to the factors affecting the mechanical properties of them. Lastly, the clinical applications and prospects of this novel drug targeting strategy were discussed. It is hoped that, with a better understanding of shear stress-sensitive carriers and their targeted principle, a novel targeted drug delivery strategy will be one day applied in the clinics of the future.

Mechanism for doping induced p type C60 using thermally evaporated molybdenum trioxide (MoO3) as a dopant.

Thermally evaporated molybdenum trioxide (MoO3) doped C60 films, which could change n type features of pristine C60 to form a p type mixed C60 layer, are investigated by x-ray and ultraviolet photoelectron spectroscopy. It is found that C60 HOMO progressively shifts closer to the Fermi level after increased MoO3 doping concentration, and final onset of C60 HOMO is pinned at binding energy of 0.20 eV, indicating the formation of p type C60 films. It is proposed that in charge transfer induced p type C60 formation, due to large electron affinity of MoO3 (6.37 eV), electrons from HOMO of C60 could easily transfer to MoO3 to form cations and therefore increase hole concentration, which could gradually push C60 HOMO to the Fermi level and finally form p type C60 films. Moreover, clear different types of C60 species have been confirmed from UPS spectra in highly doped films.