Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

[Abstract] Objective To investigate the effect and possible mechanism of cell cycle-dependent kinase (Cdk)5 inhibitor Roscovitine on 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced pathological changes in brain regions associated with Parkinson’ s disease (PD) model mice. Methods The effect of Roscovitine on the relative expression levels of P25 and Cdk5 proteins was detected by Western blotting in MPP

OBJECTIVE: To investigate the effect of Rheb1 in the development of mouse megakaryocyte-erythroid progenitor cells and its related mechanism. METHODS: Rheb1 was specifically knocked-out in the hematopoietic system of Vav1-Cre;Rheb1^fl/fl mice(Rheb1^Δ/Δ mice). Flow cytometry was used to detect the percentage of red blood cells in peripheral blood and erythroid cells in bone marrow in Vav1-Cre;Rheb1^fl/fl mice and control mice. The CFC assay was used to detect the differentiation ability of Rheb1 KO megakaryocyte-erythroid progenitor cells and control cells. Real-time fluorescence quantification PCR was used to detect the relative expression of PU.1,GATA-1,GATA-2,CEBPα and CEBPβ of Rheb1 KO megakaryocyte-erythroid progenitor cells and control cells. Rapamycin was added to the culture medium, and it was used to detect the changes in cloning ability of megakaryocyte-erythroid progenitor cells from wild-type mice in vitro. RESULTS: After Rheb1 was knocked out, the development and stress response ability of megakaryocyte-erythroid progenitor cells in mice were weaken and the differentiation ability of megakaryocyte-erythroid progenitor cells in vitro was weaken. Moreover, the expression of GATA-1 of megakaryocyte-erythroid progenitor cells was decreased. Further, rapamycin could inhibit the differentiative capacity of megakaryocyte-erythroid progenitor cells in vitro. CONCLUSION Rheb1 can regulate the development of megakaryocyte-erythroid progenitor cells probably through the mTOR signaling pathway in mice.
Animals ; Cell Differentiation ; Erythrocytes ; Flow Cytometry ; Megakaryocyte-Erythroid Progenitor Cells ; Megakaryocytes ; Mice ; Signal Transduction

XueBiJing is an intravenous five-herb injection used to treat sepsis in China.The study aimed to develop a liquid chromatography-tandem mass spectrometry(LC-MS/MS)-or liquid chromatography-ultraviolet(LC-UV)-based assay for quality evaluation of XueBiJing.Assay development involved identifying marker constituents to make the assay therapeutically relevant and building a reliable one-point cali-brator for monitoring the various analytes in parallel.Nine marker constituents from the five herbs were selected based on XueBiJing's chemical composition,pharmacokinetics,and pharmacodynamics.A selectivity test(for"similarity of response")was developed to identify and minimize interference by non-target constituents.Then,an intercept test was developed to fulfill"linearity through zero"for each analyte(absolute ratio of intercept to C response,＜2％).Using the newly developed assays,we analyzed samples from 33 batches of XueBiJing,manufactured over three years,and found small batch-to-batch variability in contents of the marker constituents(4.1％-14.8％),except for senkyunolide I(26.5％).

Excessive consumption of fructose, the sweetest of all naturally occurring carbohydrates, has been linked to worldwide epidemics of metabolic diseases in humans, and it is considered an independent risk factor for cardiovascular diseases. We provide an overview about the features of fructose metabolism, as well as potential mechanisms by which excessive fructose intake is associated with the pathogenesis of metabolic diseases both in humans and rodents. To accomplish this aim, we focus on illuminating the cellular and molecular mechanisms of fructose metabolism as well as its signaling effects on metabolic and cardiovascular homeostasis in health and disease, highlighting the role of carbohydrate-responsive element-binding protein in regulating fructose metabolism.
Fructose/adverse effects* ; Homeostasis ; Humans ; Metabolic Diseases/etiology*

【Objective】 To investigate the role of transnasal ileus tube combined with somatostatin in the treatment of early postoperative inflammatory small bowel obstruction(EPISBO) in elderly patients with gastrointestinal tumor. 【Methods】 A total of 107 elderly patients with EPISBO after gastrointestinal tumor surgery were enrolled into this retrospective study. According to adopted treatment plan, they were divided into two groups: the observation group treated with transnasal ileus tube combined with somatostatin and the control group treated with nasogastric tube combined with somatostatin. Then we compared the therapeutic efficacy and adverse reactions between the two groups. 【Results】 The response rate was 98.21% in the observation group, significantly higher than 86.27% in the control group(χ²=3.910, P<0.05). Compared with those in the control group, in the observation group, we found significantly larger amounts of abdominal circumference reduction and gastrointestinal decompression in the first 48 h(P<0.05); significantly earlier stoppage of vomiting, first passage of flatus, self-defecation, disappearance of air fluid level and significantly shorter post-obstruction duration of hospitalization(P<0.05). After 8-day treatment, the inflammatory indicators was significantly decreased(P<0.05). No significant difference was found in incidence of adverse reactions between the two group(χ²= 1.874, P>0.05) . 【Conclusions】 The transnasal ileus tube combined with somatostatinis effective and safe in the treatment of EPISBO in elderly patients with gastrointestinal tumor, so it is worth popularizing in clinic.

Objective Apolipoprotein E (APOE) is mainly involved in lipid metabolism and cholesterol transport, which is important for health. To establish a pyrosequencing based method for detection of 112T>C and 158C>T single nucleotide polymorphisms (SNPs) in Apolipoprotein E gene. Methods Three amplification systems including Taq enzyme buffer from TaKaRa company (T buffer), La Taq enzyme buffer specified for G-C rich regions (L buffer) and Trans Taq enzyme buffer from TransGen company (TT buffer) were chosen to optimize PCR system and temperature by annealing at 60 °C and gradient annealing from 62 to 68 °C respectively. The specificity of this method was evaluated by comparing its results with those of Sanger sequencing. The sensitivity of this method was evaluated by gradient diluting human genomic DNA as detection template. Results According to the concentration and specificity of the products, the optimum condition was L buffer with 60℃ annealing programs. Pyrosequencing results of 20 samples were completely consistent with those of Sanger sequencing. The sensitivity of this method could be as low as 0.16 ng genomic DNA. Conclusion A method based on pyrosequencing detecting 112 and 158 polymorphisms in APOE gene was established, which can be applied in clinical personalized medicine.

Volatile organic compounds (VOCs) in ambient air can participate in photochemical reactions, which lead to the generation of secondary pollutants such as ozone and aerosol. So real-time and accurate monitoring of atmospheric VOCs plays an important role in the study of the causes of air pollution. On the basis of proton transfer reaction mass spectrometry (PTR-MS) research, a novel dipolar proton transfer reaction mass spectrometer (DP-PTR-MS) for real-time and on-line monitoring atmospheric VOCs was developed. Compared with the conventional PTR-MS with one kind of reagent ion H3O+, DP-PTR-MS had three kinds of reagent ions H3O+, OH-, (CH)2COH+, which could be switched according to the actual detection need. So DP-PTR-MS can improve the qualitative ability and expand the detection range effectively. The reagent ion H3O+can be used for detecting VOCs whose proton affinities are greater than that of H2O. The reagent ion OH-can be used to identify VOCs cooperating with the reagent ion H3O+,and can also be used for detecting some inorganic substances such as CO2. The reagent ion (CH3)2COH+can be used for accurately detecting NH3under interference elimination circumstances. The limit of detection (LOD) and sensitivity of DP-PTR-MS were measured by using six kinds of standard gases. The results showed that the LOD for detecting toluene was 7×10-12(V/V) and the sensitivity for detecting ammonia has reached 126 cps/10-9 (V/V). The ambient air in Hefei city was on-line and real-time monitored for continuous 78 hours with DP-PTR-MS. The results showed that the newly developed DP-PTR-MS could be used for long-term and real-time monitoring atmospheric VOCs with the concentration of 10-12(V/V) level. DP-PTR-MS is an important tool for the study of the causes of atmospheric pollution and the monitoring of trace VOCs emissions.

Objective To evaluate the intra-and inter-rater reliability of MyotonPRO for Achilles tendon properties measured. Methods Twenty healthy subjects were recruited to measure Achilles tendon properties using a novel hand-held Myoton-PRO device by two testers, one of the testers re-tested five days later. The reliability was assessed using in-tra-class correlation coefficient (ICC) and Bland-Altman analysis, and minimum detectable changes (MDC) was calculated. The Achilles tendon properties of the dominant or non-dominant leg was compared. The correlation between body mass and Achilles tendon properties was examined. Results The intra-rater reliabilities of Achilles tendon properties were ICCleft=0.884 and ICCright=0.904; the inter-rater reli-abilities were ICCleft=0.883 and ICCright=0.945. The MDC was 36.64 N/m. Bland-Altman plots showed good agreement. There was no significant difference in Achilles tendon properties between dominant and non-domi-nant legs (t<1.236, P>0.05). The body mass positively correlated with Achilles tendon properties (r>0.477, P<0.05). Conclusion The intra-and inter-rater reliabilities of MyotonPRO were good in measuring Achilles tendon properties in healthy subjects. No significant difference was found between dominant and non-dominant legs. The body mass positively correlated with Achilles tendon properties in healthy subjects.

Preimplantation genetic diagnosis (PGD) was developed to play a supporting role in assisted reproductive technology. With this kind of detection method, embryos with copy number variations, chromosome translocations or single mutations were excluded and the normal embryos were chosen and implanted. Theoretically, the application of these procedures could improve the implantation and pregnancy rate and help to delivery healthy offspring. PGD was considered to be more precise, higher specific and non-invasive with the appearance of microarray hybridization technology, the next generation sequencing and time-lapse monitoring technology. This paper presented a review of new Methods used in PGD, including fluorescence in situ hybridization, array comparative genomic hybridization, SNP array, next generation sequencing, MicroSeq-PGD, MaReCs, time-lapse monitoring and cfDNA-based method, and their advantages and disadvantages as well as efficacy in the procedures in which they are used.