A 5-year-old girl was admitted due to one episode of melena and one episode of hematemesis.Upon admission,gastroscopy revealed esophageal and gastric varices.Abdominal CT scan,MRI,and color Doppler ultrasound suggested cirrhosis,intrahepatic bile duct dilation,and bilateral kidney enlargement.Genetic testing identified compound heterozygous mutations in the PKHD1 gene:c.2264C>T(p.Pro755Leu)and c.1886T>C(p.Val629Ala).The c.2264C>T(p.Pro755Leu)mutation is a known pathogenic variant with previous reports,while c.1886T>C(p.Val629Ala)is a novel mutation predicted to have pathogenic potential according to Mutation Taster and PolyPhen2.The child was diagnosed with autosomal recessive polycystic kidney disease.In children presenting with gastrointestinal bleeding without obvious causes,particularly those with liver or kidney disease,consideration should be given to the possibility of autosomal recessive polycystic kidney disease,and genetic testing should be conducted for definitive diagnosis when necessary.

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

Aim To systematically evaluate the heat-clearing mechanism of Arnebiae Radix on two mouse models of blood heat syndrome. Methods The drug-forming molecules were screened by comprehensive network pharmacology methods, and the correlation between drug efficacy and related factors and targets was evaluated on the mouse model of short effect blood heat syndrome constructed by 2, 4-dinitrophenol (DNP) and the mouse model of severe blood heat syndrome (heat stroke) constructed by high temperature combined with lipopolysaccharide (LPS). Results A total of 277 shikonin related targets were collected, mainly involving biological processes such as inflammatory reaction, oxidation reaction and coagulation reaction. Shikonin, a representative compound, significantly improved the main syndromes of mice with blood heat syndrome, reduced the levels of inflammatory factors IL-1β, IL-6 and TNF-α in the two models, and reduced the contents of oxidative damage indexes LPO and MDA, and the two showed correlation. The main mechanism was to inhibit the expression of NF-ΚB p65 and up-regulate the expression of Nrf2. Conclusions Shikonin plays a pharmacological role in the prevention and treatment of blood heat syndrome by inhibiting inflammation and improving antioxidant capacity, which provides a pharmacological basis for shikonin in the prevention and treatment of blood heat syndrome.

Objective:To understand the reliability and validity of quality of life instruments for cancer patients-brain neoplasm [QLICP-BN (V1.0)], a self-developed quality of life scale for cancer patients.Methods:The quality of life of 112 patients with brain neoplasms in Yunnan Cancer Hospital from March 2012 to November 2013 was measured. The general data questionnaire and QLICP-BN (V1.0) were used for data collection. The reliability, validity and responsiveness of the scale were tested, and then the metric characteristics of the scale were evaluated.Results:The split-half reliability of the total score of the scale was 0.95, the Cronbach αcoefficient was 0.92, and the test-retest correlation coefficient rwas 0.78. After extracting common factors by the principal component method and rotating with the maximum variance, the specific module obtained three principal components, and the cumulative variance contribution rate was 64.18%. The score of specific module was 75.30±17.44 before treatment and 78.91±12.20 after treatment ( t=-2.481, P=0.015). The total score of scale before treatment was 65.26±12.29, and that after treatment was 69.62±10.41, with a statistically significant difference ( t=-4.492, P<0.001). The total responsiveness of the scale was 0.456, showing moderate responsiveness. Conclusion:QLICP-BN (V1.0) has good reliability, validity and a certain degree of responsiveness. It can be used as a measurement tool for the quality of life of patients with brain neoplasms in China.

OBJECTIVE: To establish a method for simultaneous determination of 15 kinds of vapor state organic acids in workplace air by solvent desorption-gas chromatography.METHODS: A total 15 kinds of vapor state organic acids such as acetic acid, propanoic acid, butyric acid and pentanoic acid in the air of workplace were collected by silica gel, eluted with acetone, separated by DB-FFAP capillary chromatograph column, and detected by gas chromatography with flame ionization detection. RESULTS: There was a good linear relationship in the selected range of 15 kinds of organic acids. The coefficient correlation was 0.999 97-0.999 98. The limit of detection of this method was 0.04-0.29 mg/L, and the minimum detection concentration was 0.03-0.19 mg/m~(3 )(collected sample volume was 1.50 L). The average desorption efficiency was 92.9%-98.5%. The within-run and between-run relative standard deviation was 0.3%-1.6% and 1.5%-3.0%, respectively. The samples could be kept for at least 15 days at room temperature. CONCLUSION: The method is simple for operation, with high sensitivity, and good precision, which is suitable for simultaneous determination of 15 kinds of vapor state organic acids in the air of workplace and sites of emergency accident.

Purpose: This study was performed to establish and validate a nomogram for predicting the overall survival in children with neuroblastoma. Methods: The latest clinical data of neuroblastoma in Surveillance, Epidemiology, and End Results (SEER) database was extracted from 2000 to 2016. The cases included were randomly divided into training and validation cohorts. The survival curves were drawn with a Kaplan-Meier estimator to investigate the influences of certain single factors on overall survival. Also, least absolute shrinkage and selection operator regression was applied to further select the prognostic variables for neuroblastoma. Additionally, receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the accuracy of the nomogram. Results: In total, 1,262 patients were collected and 8 independent prognostic factors were achieved, including patients’ age, sex, race, tumor grade, radiotherapy, chemotherapy, tumor site, and tumor size. Then we constructed a nomogram by using the data of the training cohort with 886 cases. Subsequently, the nomogram was validated internally and externally with 886 and 376 cases, respectively. The internal validation revealed that the area under the curves (AUC) of ROC curves of 1-, 3-, and 5-year overall survival were 0.69, 0.78, and 0.81, respectively. Accordingly, the external validation also showed that the AUC of 1-, 3-, and 5-year overall survival were all ≥0.69. Both methods of validation demonstrated that the predictive calibration curves were consistent with standard curves. Conclusion The nomogram possess the potential to be a new tool in predicting the survival rate of neuroblastoma patients.

Oleanolic acid (OA) is a pentacyclic triterpenoid compound extracted from olea europaeal, a traditional Chinese medicine herb. OA has been used in the clinic as a hepatoprotective medicine in China since 1970s. In our previous study, we observed that OA could ameliorate hyperlipidemia in animal models. In the present study, we conducted a small-scale clinical trial to evaluate the hypolipidemia effect of OA in hyperlipidemic patients. Hyperlipidemic patients were administrated with OA for four weeks (4 tablets once, three times a day). The blood samples of the patients were collected before and after OA treatment. The biological parameters were measured. Furthermore, three patients' blood samples were studied with DNA microarray. After OA administration, the TC, TG, and HDLC levels in serum decreased significantly. DNA microarray analysis results showed that the expressions of 21 mRNAs were significantly changed after OA treatment. Bioinformatics analysis showed 17 mRNAs were up-regulated and 4 mRNAs were down-regulated significantly after OA treatment. Five mRNAs (CACNA1B, FCN, STEAP3, AMPH, and NR6A1) were selected to validate the expression levels by qRT-PCR. Therefore, OA administration differentially regulated the expression of genes involved in lipid metabolism. The data showed a clinical evidence that OA could improve hyperlipidemia and also unveiled a new insight into the molecular mechanisms underlying the pharmacological effect of OA on hyperlipidemia.
China ; Computational Biology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; drug effects ; Humans ; Hyperlipidemias ; blood ; drug therapy ; genetics ; metabolism ; Lipid Metabolism ; drug effects ; Male ; Middle Aged ; Oleanolic Acid ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; Treatment Outcome

OBJECTIVETo investigate the features of white matter myelin development in preterm infants using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI).

METHODSA total of 31 preterm infants with a gestational age of ≤32 weeks and a birth weight of <1 500 g were enrolled. According to head MRI findings, these infants were divided into preterm group with brain injury (12 infants) and preterm group without brain injury (19 infants). A total of 24 full-term infants were enrolled as control group. Head MRI and DTI were performed at a gestational age or corrected gestational age of 37-40 weeks. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured for the same regions of interest in the three groups.

RESULTSThe preterm group with brain injury showed a significantly lower FA value of the posterior limb of the internal capsule than the preterm group without brain injury and full-term control group (P<0.05). The preterm groups with and without brain injury showed significantly lower FA values of frontal white matter and lenticular nucleus than the full-term control group (P<0.05). The FA value of occipital white matter showed no significant differences among the three groups (P>0.05). Compared with the full-term control group, the preterm groups with and without brain injury showed significantly higher ADC values of the posterior limb of the internal capsule, lenticular nucleus, occipital white matter, and frontal white matter (P<0.05).

CONCLUSIONSAfter brain injury, preterm infants tend to develop disorder or delay of white matter myelination in the posterior limb of the internal capsule. At a corrected full-term gestational age, the preterm infants with and without brain injury have a lower grade of maturity in periventricular white matter and grey matter than full-term infants.

Brain Injuries ; physiopathology ; Diffusion Tensor Imaging ; methods ; Humans ; Infant, Newborn ; Infant, Premature ; physiology ; Magnetic Resonance Imaging ; methods ; Myelin Sheath ; physiology ; White Matter ; growth & development

Objective To systematically evaluate the efficacy and safety of amlodipine (A)/hydrochlorothiazide(H) versus val‐sartan(V)/hydrochlorothiazide(H) in treatment of essential hypertension .Methods Literature was retrieved online in Cochrane Li‐brary ,PubMed ,OVID ,MEDLINE ,EMBASE ,CBM ,CNKI ,VIP and Wan fang database up to November 2013 .Relevant magazines were retrieved manually .Quality of the included studies was assessed and Meta‐analysis was performed with RevMan 5 .2 software . Results Seven randomized controlled trials(RCTs) were finally included .Meta‐analyses showed that :in terms of lowering ABP ,V/H group was more effective than A/H group ,the difference was statistically significant (P<0 .05);there was no significant differ‐ence in the decreased value of clinic BP and the control rate of blood pressure between A /H group and V/H group(P>0 .05) .Ad‐verse events occurred less frequently with V/H group compared with A/H group ,the difference was statistically significant (P<0 .05) .Conclusion A/H treatment of essential hypertension is inferior to V/H ,and has more adverse events .

Applications of network pharmacology are increasingly widespread and methods abound in the field of drug development and pharmacological research. In this study, we choose rosiglitazone compound as the object to predict the targets and to discuss the mechanism based on three kinds of prediction methods of network pharmacology. Comparison of the prediction result has identified that the three kinds of prediction methods had their own characteristics: targets and pathways predicted were not in accordance with each other. However, the calcium signaling pathway could be predicted in the three kinds of methods, which associated with diabetes and cognitive impairment caused by diabetes by bioinformatics analysis. The above conclusion indicates that the calcium signaling pathway is important in signal pathway regulation of rosiglitazone compound, which provides a clue to further explain the mechanism of the compound and also provides a reference for the selection and application of methods of network pharmacology in the actual research.
Calcium Signaling ; Cognitive Dysfunction ; Computational Biology ; Diabetes Mellitus ; Humans ; Pharmacology ; methods ; Thiazolidinediones ; pharmacology