Poria is an important medicine for inducing diuresis to drain dampness from the middle energizer. However, the specific effective components and the potential mechanism of Poria remain largely unknown. To identify the effective components and the mechanism of Poria water extract (PWE) to treat dampness stagnancy due to spleen deficiency syndrome (DSSD), a rat model of DSSD was established through weight-loaded forced swimming, intragastric ice-water stimulation, humid living environment, and alternate-day fasting for 21 days. After 14 days of treatment with PWE, the results indicated that PWE increased fecal moisture percentage, urine output, D-xylose level and weight; amylase, albumin, and total protein levels; and the swimming time of rats with DSSD to different extents. Eleven highly related components were screened out using the spectrum-effect relationship and LC-MS. Mechanistic studies revealed that PWE significantly increased the expression of serum motilin (MTL), gastrin (GAS), ADCY5/6, p-PKAα/β/γ cat, and phosphorylated cAMP-response element binding protein in the stomach, and AQP3 expression in the colon. Moreover, it decreased the levels of serum ADH, the expression of AQP3 and AQP4 in the stomach, AQP1 and AQP3 in the duodenum, and AQP4 in the colon. PWE induced diuresis to drain dampness in rats with DSSD. Eleven main effective components were identified in PWE. They exerted therapeutic effect by regulating the AC-cAMP-AQP signaling pathway in the stomach, MTL and GAS levels in the serum, AQP1 and AQP3 expression in the duodenum, and AQP3 and AQP4 expression in the colon.
Animals ; Rats ; Poria ; Spleen ; Albumins ; Chromatography, Liquid ; Cyclic AMP Response Element-Binding Protein

Objective:This study was to systematically update the economic evaluation evidence of colorectal cancer screening in mainland China.Methods:Based on a systematic review published in 2015, we expanded the scope of retrieval database (PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, CBM) and extended it to December 2018. Focusing on the evidence for nearly 10 years (2009-2018), basic characteristics and main results were extracted. Costs were discounted to 2017 using the consumer price index of medical and health care being provided to the residents, and the ratio of incremental cost-effectiveness ratio (ICER) to per capita GDP in corresponding years were calculated.Results:A total of 12 articles (8 new ones) were included, of which 9 were population-based (all cross-sectional studies) and 3 were model-based. Most of the initial screening age was 40 years (7 articles), and most of the frequency was once in a lifetime (11 articles). Technologies used for primary screening included: questionnaire assessment, immunological fecal occult blood test (iFOBT) and endoscopy. The most commonly used indicator was the cost per colorectal cancer detected, and the median (range) of the 20 screening schemes was 52 307 Chinese Yuan (12 967-3 769 801, n=20). The cost per adenoma detected was 9 220 Yuan (1 859-40 535, n=10). In 3 articles, the cost per life year saved (compared with noscreening) was mentioned and the ratio of ICER to GDP was 0.673 (-0.013-2.459, n=11), which was considered by WHO as "very cost-effective" ; The range of ratios overlapped greatly among different technologies and screening frequencies, but the initial age for screening seemed more cost-effective at the age of 50 years (0.002, -0.013-0.015, n=3), than at the 40 year-olds (0.781, 0.321-2.459, n=8). Conclusions:Results from the population-based studies showed that the cost per adenoma detected was only 1/6 of the cost per colorectal cancer detected, and limited ICER evidence suggested that screening for colorectal cancer was generally cost-effective in Chinese population. Despite the inconclusiveness of the optimal screening technology, the findings suggested that the initial screening might be more cost-effective at older age. No high-level evidence such as randomized controlled trial evaluation was found.

Objective To explore the relationship between heart rate variability (HRV),heart rate turbulence (HRT) and blood pressure (BP) control in hypertensive patients.Methods Hypertensive patients with controlled BP group (n =50) and uncontrolled BP group (n =40) and control group non-hypertensive patients (n =52)were enrolled in this study in our hospital during June 2015 to June 2016.HRV and HRT as well as clinical characteristic of the three groups were analyzed.Results (1) Body mass index was significantly higher in the controlled BP group than in the control group.There was no statistical difference in proportions and categories of antihypertensive medication between the uncontrolled and controlled BP groups (P ＞ 0.05).(2) VLF,LF and TS were significantly lower in the uncontrolled BP group than the control group,and HF was significantly lower in the uncontrolled BP group than in the controlled BP group (P ＜ 0.05).(3) Results of muhiple logistic regression analysis showed that lower rMSSD,pNN50,VLF,LF,HF and TS were risk factors for BP control after adjusting for gender,age,EF value,creatinine,blood lipids,Beta-blockers and history of smoking,coronary heart disease and diabetes mellitus.(4) Spearman correlation analysis of the hypertensive patients showed that LF was negatively correlated with TO,and SDNN,SDANN,rMSSD,pNN50,VLF,LF,HF were positively correlated with TS.Conclusion The present results demonstrate that uncontrolled BP is associated with abnormal HRV and HRT,which suggested autonomous nervous imbalance was existed in uncontrolled hypertensive patients.

Objective: To assess the feasibility and prognostic value of the minimal residual disease (MRD) evaluated by multiparameter flow cytometry (MFC) in the newly diagnosed multiple myeloma (MM) patients of China. Methods: Clinical data of 106 consecutively newly diagnosed MM patients with MRD data were retrospectively analyzed in a single center in China from June 2013 to June 2015. Results: ① Of 106 patients, 48 (45.3%) achieved MRD negativity. The median time to MRD-negative was 3 months. More patients undergoing autologous stem cell transplantation (ASCT) achieved MRD negativity compared with non-ASCT patients (62.2% vs 36.2%, χ²=6.536, P=0.011). ② Of 48 patients in complete remission (CR), 7 (14.6%) was MRD positive, 5 of them showed disease progression (PD) during the follow-up, and 3 died. The median progression free survival (PFS) was 19 months, and the median overall survival (OS) was 28 months, both were significantly shorter than the CR patients with MRD-negative (P<0.05). ③At a median follow-up of 38 months, MRD-negative patients showed significantly superior outcomes compared with MRD positive ones, the PFS was not reach versus 17 months and the OS was not reach for both (P<0.001). Patients were grouped into 4 categories according to their MRD levels: 1% or higher, 0.1% to less than 1%, 0.01% to less than 0.1%, or negative. It showed that the outcomes (PFS and OS) tended to be improved along with the tumor depletion. ④ Multivariate prognostic analysis showed that MRD was a powerful independent prognostic factor for PFS[HR=0.133 (95% CI 0.062-0.288) , P<0.001] and OS[HR=0.156 (95% CI 0.050-0.484) , P=0.001]. According to MRD and cytogenetics, the patients were classified into 4 groups. High risk patients with MRD negative presented a significantly better outcome than high risk patients with MRD-positive, and a similar one to the standard risk patients with MRD-negative. Conclusions MRD negativity by MFC was more popular in MM patients undergoing ASCT. MRD was an independent prognostic factor in MM. And the prognosis of MM patients can be stratified according to the level of MRD. MRD-negative patients with high risk cytogenetics presented a similar outcome to the standard risk ones. MRD by MFC should therefore be considered more widely applied in the clinic.

Trace impurities of Al, Ca, Co, Fe, K, Mg, Mn, Na, Ni in silicon nitride powder were determined by slurry introduction into a solution-cathode glow discharge-atomic emission spectrometer (SCGD-AES).The effect of particle size on the stability of suspension was investigated.A 6-port valve was selected to link sampling system and SCGD-AES, by which the suspension could be introduced into the SCGD-AES to get instantaneous spectrum signal.The calibration curves for quantitative analysis could be established using aqueous standards and the pH of suspension was not required to be adjusted accurately.The applied voltage, solution flow rate, and integral time of PMT were set to 1080 V, 1.2 mL/min and 800 ms, respectively.In this work, slurry sampling was combined with SCGD-AES by a 6 port 2-pos valve.Powder Si3N4 was tested by this way and the limits of detection for all nine elements were 0.2-53.0 mg/kg.The RSDs were 1.1%-5.0%.The detection result of trace impurities in standard reference material ERM-ED101 agreed with that obtained from inductively coupled plasma atomic emission spectrometry.This method was proved to be accurate, reliable and valuable.

Laser ablation inductively coupled plasma mass spectrometry ( LA_ICP_MS ) was applied for the determination of doping element chromium( Cr) content and distribution in Cr∶ZnSe crystals. Several different Cr∶ZnSe crystals were prepared by diffusion method as reference material to solve the problem of accurate quantization. The homogeneity of Cr in these samples was characterized by LA_ICP_MS and the concentrations achieved by inductively coupled plasma atomic emission spectrometry ( ICP_AES ) . With signal pot and line scan sampling, the present method provided effective position and content distribution information of Cr in ZnSe crystals, achieved the in situ analysis. The correlation coefficient of Cr in calibration curve was 0. 9992 and the detection limit was 0. 08 mg/kg. It could provide effective means for the distribution statistics of doping element in different growth condition crystals.

AIM: To investigate whether glucosylceramide synthase (GCS) regulates apoptosis-related gene bcl-2 expression via MEK/ERK signaling pathway , thus enhancing drug resistance of K 562/A02 human leukemia multidrug resistant cell line.METHODS:siRNA targeting GCS was transfected into K562/A02 cells.Bcl-2, p-ERK and total ERK expression at mRNA and protein levels after GCS knockdown were detected by real-time PCR and Western blotting .After exposed to MEK-ERK pathway inhibitor U0126, the expression of Bcl-2 at mRNA and protein levels also was analyzed by real-time PCR and Western blotting , respectively.The viability of the cells was evaluated by CCK-8 assay.RESULTS:The expression of GCS and Bcl-2, as well as MEK/ERK signaling were significantly inhibited in K 562/A02 cells by GCS siRNA transfection compared with negative control group .Inactivation of MEK/ERK signaling due to U0126 treatment de-creased Bcl-2 mRNA and protein levels in a concentration-dependent manner , and sensitized K562/A02 cells to adriamy-cin.CONCLUSION:GCS may affect the expression of apoptosis-related gene bcl-2 by MEK/ERK signaling pathway , thus regulating multidrug resistance of human leukemia K 562/A02 cells.

TheLutetium-YttriumOrthosilicate(LYSO)isakindofscintillatingcrystalmaterialwiththebest comprehensive properties. In this work, the trace elements Ca, Fe, K, Li, Mg and Na in LYSO were determined by solution-cathode glow discharge-atomic emission spectrometry ( SCGS-AES ) . The optimal conditions included 0. 1 mol/L HNO3 sample solutions and operation at a voltage at 1080 V with a flow rate of 2. 0 mL/min. The LYSO matrix concentration tolerance of the SCGD source was determined to be 10 g/L. Sample solutions dissolving from several LYSO samples with HF, HNO3 and HClO4 were examined by SCGD-AES. For LYSO samples, the values obtained by SCGD-AES agree well with those obtained by axial inductively coupled plasma-atomic emission spectroscopy ( ICP-AES ) and inductively coupled plasma-mass spectroscopy (ICP-MS). The emissions of Lu and Y were not observed, so that the determination of trace elements in LYSO matrices could be conducted with little interference. The detection limits of Ca, Fe, K, Li, Mg and Na in LYSO were 1. 0, 3. 0, 0. 02, 0. 01, 0. 02 and 1. 0 mg/kg, respectively.

OBJECTIVETo investigate whether transcription factor-kappaB (NF-κ B) is involved in the modulation of P-glycoprotein (P-gp) by glucosylceramide synthase (GCS) in a multidrug resistance leukemia cell line K562/A02 and to explore the relationship between NF-κ B and extracelluar signal-regulated kinase (ERK).

METHODSK562/A02 cells were treated with GCSsiRNA, pyrrolidine dithiocarbamate (PDTC, a NF-κ B specific inhibitor) and U0126 (a MEK1/2 inhibitor), respectively. The expression of GCS and multidrug resistance protein 1 (MDR1) mRNA were analyzed with qRT-PCR. Various proteins of different groups were measured by Western blotting.

RESULTSAfter transfected with GCSsiRNA for 48 h, GCS mRNA were reduced by 62% (51%-73%) and MDR1 mRNA was reduced by 52% (43%-61%) in the K562/A02 cells. Compared with the negative control, relative expression of NF-κ B p65 in nuclear and P-ERK1/2 were both down-regulated, and P-gp was also inhibited significantly at 72 h after transfected with GCSsiRNA (P< 0.05). In addition, the expression of P-gp was decreased at 24 h with 80 μ mol/L PDTC and 48 h with 20 μ mol/L PDTC. P-ERK1/2 was inhibited significantly when the cells were treated with 20 μ mol/L U0126 for 48 h. The expression of NF-κ B p65 in nuclear and P-gp were also down-regulated.

CONCLUSIONNF-κ B can modulate the effect of GCS on P-gp in K562/A02 cells. P-ERK1/2 can activate NF-κ B in above signal transduction pathway.

ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Cell Line, Tumor ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Glucosyltransferases ; genetics ; metabolism ; Humans ; K562 Cells ; Leukemia ; genetics ; NF-kappa B ; genetics ; metabolism

OBJECTIVETo estimate the significance of the adjustment of acute lymphoblastic leukemia (ALL) risk group by monitoring minimal residual disease(MRD).

METHODTotally 285 children ALL patients who were diagnosed and systematically treated according to CCLG-2008 in Institute of Hematology and Blood Diseases Hospital, CAMS and PUMC, from April 2008 to August 2011 were prospectively selected. Among these cases, 62.8% (n = 179) were boys and 37.2% (n = 106) were girls and the median age was 5.3(0.5-14.0). The patients who were at high-risk group initially were excluded. The grouping of cases: the patients were divided into two groups according to the dates of initial diagnosis. Group I had 126 patients who were initially diagnosed between April 2008 and December 2009 in whom therapeutic regimen was not adjusted by reassignment of risk group by MRD. Group II had 159 patients who were initially diagnosed between January 2010 and August 2011 whose therapeutic regimen was adjusted by reassignment of risk group by MRD at specific time (33rd day of induction chemotherapy and 12 weeks after the beginning of chemotherapy). MP-FCM Coulter FC-500 was used in the detection of MRD.

RESULTAmong these 285 patients, 94.0% (n = 268) were diagnosed as B-lineage acute lymphoblastic leukemia and 6.0% (n = 17) were T-lineage acute lymphoblastic leukemia. In group I, 61.9% (n = 78) patients belonged to low-risk group, 38.1% (n = 48) median-risk; in group II, before the adjustment, the rates of the low-risk group and median-risk group were 68.6% (n = 109) and 31.4% (n = 50) , respectively, while after the adjustment they were altered to 53.5% (n = 85) and 39.6% (n = 63) , furthermore 6.9% (n = 11) patients went into the high-risk group. Both groups were followed up for 2.5 years after their diagnoses, the disease of 7.4% (n = 21) patients relapsed, and the rates of two groups were 12.7% (n = 16) and 3.1% (n = 5) respectively, P = 0.009. The rate of serious infection (such as sepsis, pulmonary infection) of all these patients was 32.3% (92/285) , there was no significant difference between the two groups [28.6% (36/126) vs.35.2% (56/159) , P = 0.392]. The mortality of all these patients was 6.7% (19/285) , and that of group I was higher than that of group II [10.3% (13/126) vs. 3.8% (6/159) , P = 0.044]. The 2.5 years overall survival (OS), event-free survival (EFS) and disease-free survival (DFS) of group I were all lower than those of group II in Kaplan-Meier survivorship analysis (all P < 0.05). The two groups were followed up for 2.5 years after their diagnoses, after elimination of the confounding influence of sex, age, FAB subtype, WBC count, ratio of blast cells in bone marrow at diagnosed, chromosome karyotype and fusion gene, reassignment of risk group by MRD was used to calculate the OS, EFS and DFS of ALL patients (all P < 0.05). After the adjustment the risk group was more significant in the assessment of prognosis.

CONCLUSIONThe reassignment of risk group in low and median risk groups children with acute lymphoblastic leukemia by MRD did not increase the rate of serious infection but could reduce the relapse rate and mortality, and was beneficial to increase the patients' OS, EFS and DFS.

Adolescent ; Antineoplastic Agents ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Bone Marrow ; pathology ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Flow Cytometry ; Humans ; Infant ; Male ; Neoplasm, Residual ; diagnosis ; drug therapy ; pathology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; diagnosis ; drug therapy ; pathology ; Prognosis ; Prospective Studies ; Recurrence ; Remission Induction ; Survival Rate ; Treatment Outcome