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.

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.

OBJECTIVES: To investigate the relationship between gene mutations and response to Compound Qinghuang Powder (, CQHP) in patients with myelodysplastic syndrome (MDS). METHODS: Forty-three MDS patients were genotyped by ultra-deep targeted sequencing and the clinical data of patients were collected and the relationship between them was analyzed. RESULTS: Up to 41.86% of patients harbored genet mutations, in most cases with more than one mutation. The most common mutations were in SF3B1, U2AF1, ASXL1, and DNMT3A. After treatment with CQHP, about 88.00% of patients no longer required blood transfusion, or needed half of prior transfusions. CONCLUSIONS CQHP is an effective treatment for patients with MDS, especially those with gene mutations in SF3B1, DNMT3A, U2AF1, and/or ASXL1.

BACKGROUNDPlasmacytoid dendritic cells (pDCs) and cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to explore the frequency and function of pDC and serum cytokine network profiles in patients with acute or chronic HBV infection.

METHODSThe healthy individuals (HI group), hepatitis B envelope antigen (HBeAg)-positive chronic HBV patients in immune tolerance (IT) phase (IT group), HBeAg-positive chronic HBV patients (CHB group), and acute HBV patients (AHB group) were enrolled in this study. The frequency of cluster of differentiation antigen 86 (CD86) + pDC and the counts of CD86 molecular expressed on surface of pDC were tested by flow cytometer. The quantitative determinations of cytokines, including Fms-like tyrosine kinase 3 ligand (Flt-3L), interferon (IFN)-α2, IFN-γ, interleukin (IL)-17A, IL-6, IL-10, transforming growth factor (TGF)-β1 and TGF-β2, were performed using Luminex multiplex technology.

RESULTSIn this study, there were 13 patients in HI group, 30 in IT group, 50 in CHB group, and 32 in AHB group. Compared with HI group, HBV infected group (including all patients in IT, CHB and AHB groups) had significantly higher counts of CD86 molecular expressed on the surface of pDC (4596.5 ± 896.5 vs. 7097.7 ± 3124.6; P < 0.001). The counts of CD86 molecular expressed on the surface of pDC in CHB group (7739.2 ± 4125.4) was significantly higher than that of IT group (6393.4 ± 1653.6, P = 0.043). Compared with IT group, the profile of cytokines of Flt-3L, IFN-γ, and IL-17A was decreased, IFN-α2 was significantly increased (P = 0.012) in CHB group. The contents of IL-10, TGF-β1, and TGF-β2 in AHB group were significantly increased compared with IT and CHB groups (all P < 0.05).

CONCLUSIONSThis study demonstrated that the function of pDC was unaffected in HBV infection. The enhanced function of pDC and IFN-α2 might involve triggering the immune response from IT to hepatitis active phase in HBV infection. Acute patients mainly presented as down-regulation of the immune response by enhanced IL-10 and TGF-β.

Objective To establish a clinical method for early detection of the bloodstream infection bacteria based on matrix-assisted laser ionization time of flight mass spectrometry (MALDI-TOF MS).Methods After consulting the Laboratory Information System statistics and domestic related literature,We chose 10 kinds of bacteria (Escherichia coli.,Pseudomonas aeruginosa,Acinetobacter baumannii,Klebsiella pneumoniae,Enterococcus faecium,Enterococcus faecalis,Staphylococcus aureus and Staphylococcus epidermidis,Proteus mirabilis,Streptococcus pneumoniae) as target.The MALDI-TOF MS was established using simulated bacterial infection blood samples.From March to May 2017,33 blood samples of suspected sepsis patients from Emergency Department,General Hospital of PLA,were tested.Results The MALDI-TOF MS whose detecting sensitivity was 100CFU/ml had the same negative detection rate with the blood culture (27cases/27cases,100％).Besides the 2 samples of Morganella morganii infection and Staphylococcus hominis infection were out of the range,the results of the remaining 4 positive samples were consistent (100％).Conclusion Compared to the blood culture and biochemical identification,MALDI-TOF MS can rapidly detect 10 kinds of bloodstream infection bacteria with high sensitivity and high accuracy.

Background: Cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to investigate the changes of cytokines concentration and its correlation to alanine aminotransferase (ALT), HBV deoxyribonucleic acid (HBV-DNA), hepatitis B envelope antigen (HBeAg), and HBV surface antigen (HBsAg) in the development of chronic hepatitis B (CHB). Methods: Thirteen healthy individuals (HI), 30 chronic HBV-infected patients in immune tolerant (IT) phase, and 55 CHB patients were enrolled between August 2015 and May 2017. The peripheral blood samples were collected from all individuals. The levels of interferon (IFN)-α2, interleukin (IL)-10, transforming growth factor (TGF)-β1, HBV-DNA, HBsAg, and HBeAg and liver function were measured. The quantitative determinations of cytokines levels, including IFN-α2, IL-10, and TGF-β1 were performed using Luminex multiplex technology. The correlation of cytokines to ALT, HBV-DNA, HBsAg, and HBeAg was analyzed by linear regression analysis. Results: IFN-α2 levels were similar between HI and IT groups (15.35 [5.70, 67.65] pg/ml vs. 15.24 [4.07, 30.73] pg/ml, Z = -0.610, P = 0.542), while it elevated significantly in CHB group (35.29 [15.94, 70.15] pg/ml vs. 15.24 [4.07, 30.73] pg/ml; Z = -2.522, P = 0.012). Compared with HI group (3.73 [2.98, 11.92] pg/ml), IL-10 concentrations in IT group (5.02 [2.98, 10.11] pg/ml), and CHB group (7.48 [3.10, 18.00] pg/ml) slightly increased (χ = 2.015, P = 0.365), and there was no significant difference between IT and CHB group (Z = -1.419, P = 0.156). The TGF-β1 levels among HI (3.59 ± 0.20 pg/ml), IT (3.62 ± 0.55 pg/ml), and CHB groups (3.64 ± 0.30 pg/ml) were similar (χ = 2.739, P = 0.254). In all chronic HBV-infected patients (including patients in IT and CHB groups), the elevation of IFN-α2 level was significantly associated with ALT level (β= 0.389, t = 2.423, P = 0.018), and was also negatively correlated to HBV-DNA load (β = -0.358, t = -2.308, P = 0.024), HBsAg (β = -0.359, t = -2.288, P = 0.025), and HBeAg contents (β = -0.355, t = -2.258, P = 0.027). However, when both ALT level and cytokines were included as independent variable, HBV-DNA load, HBsAg, and HBeAg contents were only correlated to ALT level (β = -0.459, t = -4.225, P = 0.000; β = -0.616, t = -6.334, P = 0.000; and β = -0.290, t = -2.433, P = 0.018; respectively). Conclusions IFN-α2 elevation was associated with ALT level in patients with chronic HBV infection. However, in CHB patients, only ALT level was correlated to HBV-DNA, HBsAg and HBeAg contents.
Adult ; Alanine Transaminase ; blood ; Antigens, Surface ; Case-Control Studies ; Cytokines ; blood ; DNA, Viral ; Female ; Hepatitis B ; Hepatitis B Surface Antigens ; analysis ; Hepatitis B e Antigens ; Hepatitis B virus ; Hepatitis B, Chronic ; blood ; immunology ; Humans ; Male ; Young Adult

Poria cocos (Schw.) Wolf, an important medicinal and food fungus, is well known in East Asia. Due to growing market demand, long cultivation period, and consumption of pine trunk during cultivation, developing alternative methods for producing P. cocos and/or its active components is of interest. In the present study, the effects of different culture methods on biomass and accumulation of four triterpenoids were investigated. The ethanol extract of fermented mycelium (EFM) was orally administered to rats. Urine output and concentrations of electrolytes (Na, K, and Cl) were measured. Our results showed that mycelia grew better under continuous shaking culture condition (7.5 g DW·L), and higher triterpenoid levels were accumulated in two-stage culture (112 mg·L, 2.03%). The optimal starting time of static culture for triterpenoid yield was 4 d after shaking culture. Single administration of middle and high dose of EFM significantly increased urine output, Na and Cl excretion, and Na/K ratio. These results suggested that ethanol extract of cultured mycelia showed significant diuretic activity in rats and two-stage culture of P. cocos could be an alternative way to produce mycelia and triterpenoids.
Animals ; Biomass ; Diuretics ; pharmacology ; Mycelium ; chemistry ; growth & development ; Rats ; Triterpenes ; metabolism ; Wolfiporia ; chemistry ; growth & development

This cohort study was designed to evaluate the association of transcription factor 7-like 2 (TCF7L2) and proglucagon gene (GCG) variants with disordered glucose metabolism and the incidence of type 2 diabetes mellitus (T2DM) in a rural adult Chinese population. A total of 7,751 non-T2DM participants ⋝18 years old genotyped at baseline were recruited. The same questionnaire interview and physical and blood biochemical examinations were performed at both baseline and follow-up. During a median 6 years of follow-up, T2DM developed in 227 participants. After adjustment for potential contributory factors, nominally significant associations were seen between TT genotype and the recessive model of TCF7L2 rs7903146 and increased risk of T2DM [hazard ratio (HR)=4.068, 95% confidence interval (CI): 1.270-13.026; HR=4.051, 95% CI: 1.268-12.946, respectively]. The TT genotype of rs7903146 was also significantly associated with higher fasting plasma insulin level and the homeostasis model assessment of insulin resistance in case of new-onset diabetes. In addition, the TCF7L2 rs290487 TT genotype was associated with abdominal obesity and the GCG rs12104705 CC genotype was associated with both general obesity and abdominal obesity in case of new-onset diabetes.
Adult ; Cohort Studies ; Diabetes Mellitus, Type 2 ; complications ; genetics ; Female ; Humans ; Insulin ; secretion ; Insulin Resistance ; genetics ; Male ; Middle Aged ; Obesity ; complications ; genetics ; Polymorphism, Single Nucleotide ; Proglucagon ; genetics ; Transcription Factor 7-Like 2 Protein ; genetics

Objective To compared the influence on inflammatory factors of using ticagrelor and clopidogrel in patients with coronary heart disease after percutaneous coronary intervention ( PCI ) operation . Methods A total of 110 patients with coronary heart disease after PCI were divided into treatment group and control group ,55 cases in each group.Treatment group was given ticagrelor 90 mg, qd, and control group given clopidogrel 300 mg, qd.The course of two groups were both one month .The throm-bolysis in myocardial infarction ( TIMI ) blood flow and no reflow incidence of two groups were compared after treat-ment.Inflammatory factor C-reactive protein (CRP), interleukin 6 (IL-6), myelo peroxidase(MPO), and soluble CD40 receptor (sCD40L) levels were compared of the two groups before surgery and 1 week, 1, 3 and 6 months after treatment.The incidence of major cardiovascular adverse events was compared of two groups .Results There was no reflow case found in treatment group , and two cases of no reflow were founded in control group (3.64%, P>0.05 ). The number of patients in TIMI level 3 of treatment group and control group were 53 ( 96.36%) and 44 ( 88.00%, P<0.05).The levels of CRP, IL -6, MPO, sCD40L in one week of treatment group were ( 12.05 ±1.06 ) ng? mL-1 ,(3.38 ±0.83 ) pg? mL-1 , ( 233.16 ±25.24 )μg? mL-1 , ( 632.38 ±24.99 ) pg? mL-1 , and were (10.37 ±1.88 ) ng? mL-1 ,(7.96 ±0.99 ) pg? mL-1 ,(237.06 ±20.33 )μg? mL-1 ,(624.46 ±22.33 ) pg? mL-1 in control group(P<0.05).The levels of CRP, IL-6, MPO, sCD40L in one month of treatment group were (4.68 ± 1.38)ng? mL-1,(3.13 ±1.11)pg? mL-1,(204.49 ±21.38)μg? mL-1,(588.67 ±19.55)pg? mL-1, and were (3.04 ±1.17)ng? mL-1,(2.15 ±1.29)pg? mL-1,(179.06 ±20.29)μg? mL-1,(565.27 ±21.15)pg? mL-1in control group(P<0.05).The levels of CRP, IL-6, MPO, sCD40L in three months of treatment group were (4.26 ± 0.53)ng? mL-1,(3.07 ±1.09)pg? mL-1,(198.11 ±21.25)μg? mL-1,(574.17 ±26.31)pg? mL-1, and were (2.92 ±0.97)ng? mL-1,(2.12 ±1.34)pg? mL-1,(165.19 ±25.63)μg? mL-1,(522.17 ±23.42)pg? mL-1in control group(P<0.05).The levels of CRP, IL-6, MPO, sCD40L in six months were (4.14 ±0.49)ng? mL-1, (3.05 ±1.13)pg? mL-1,(200.16 ±22.17)μg? mL-1,(363.26 ±19.48)pg? mL-1 in treatment group, and were (2.79 ±1.11)ng? mL-1,(2.08 ±1.32)pg? mL -1,(174.06 ±22.01)μg? mL-1,(323.55 ±24.63)pg? mL-1 in control group ( P <0.05 ) .The adverse reactions mainly manifested as cardiac death , atrial fibrillation , recurrent myocardial infarction , the incidence of major cardiovascular adverse events in treatment group ( 9.09%) was signifi-cantly higher than that in control group ( 7.27%, P>0.05 ) .Conclusion Ticagrelor effectively reduce the level of inflammatory reaction in patients with coronary heart disease after PCI , improve the prognosis and reduce the incidence of adverse reactions.