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.

By reviewing the organization and implementation of “Hongsha-2021” Guangxi nuclear emergency joint exercises, this article summarizes the experience in the organization process and puts forward some thoughts and suggestions in order to improve the depth of provincial-level on-site and off-site joint exercises for nuclear emergency at nuclear power plants and further enhance the emergency response capacity of nuclear emergency organizations at all levels.

Objective:To investigate the regulatory effect of Sijunzi Tang(SJZT) and its single herbs(Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma Praeparata cum Melle, Atractylodis Macrocephalae Rhizoma and Poria) on intestinal flora in spleen-deficient rats. Method:Normal rats were randomly divided into the blank group, model group, Zhengchangsheng granules group, SJZT group and each single herb group, rats were orally administered Sennae Folium decoction to induce diarrhea for ten consecutive days to establish a spleen-deficient model(distilled water for the blank group), then treated with the corresponding drugs for seven consecutive days(distilled water for the blank group and the model group). Fresh feces were collected on pre-modeling(0^th day), post-modeling(11^th day), and post-treatment(18^th day). Short-chain fatty acids(SCFAs) in feces were acidified by sulphuric acid and extracted by diethyl ether, then determined by gas chromatography. The structural change(diversity and similarity) of intestinal flora in feces was analyzed by 16S rDNA-polymerase chain reaction(PCR)-denaturing gel gradient electrophoresis(DGGE) technique. Result:Compared with blank group, the contents of SCFAs as well as diversity and similarity indexes of intestinal flora in feces of all administered groups were significantly decreased on the 11^th day(P<0.05, P<0.01), this indicated that the spleen-deficient model was successfully constructed. On the 18^th day, compared with model group, the contents of SCFAs as well as diversity and similarity indexes of intestinal flora in feces of Atractylodis Macrocephalae Rhizoma group were significantly increased(P<0.01), these indexes in feces of SJZT group, Ginseng Radix et Rhizoma group and Poria group were significantly increased(P<0.05, P<0.01), while Glycyrrhizae Radix et Rhizoma Praeparata cum Melle group only increased diversity index of intestinal flora(P<0.05). Conclusion:Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma and Poria are the single herbs responsible for the regulatory effect of SJZT on intestinal flora in spleen-deficient rats, and Atractylodis Macrocephalae Rhizoma may play a major role.

The tandem mass spectrum of apigenin-6,8-C-di-glucoside( 1) and apigenin-6-C-glucose-8-C-rhamnoside( 2) were obtained by high resolution electrospray ionization mass spectrometry( HR-ESI-MS/MS) in both positive and negative ion modes. The elemental composition of each ion was determined according to its accurate mass-to-charge,hence,the fragmentation pathways of each compound were proposed in both negative and positive ion modes. Comprehensive analysis of each ion and its proposed fragmentation pathways of the two compounds was initially conducted in both negative and positive ion mode HR-ESI-MS/MS to explore the diagnostic ions for flavone-6,8-C-di-glycosides and the characteristic ions for each compound and their cleavage rules. The results showed that a family of fragmentation ions with m/z 353,325,311,297 in ESI(-)-MS and m/z 355,325,307,295 in ESI( +)-MS could be the diagnostic ions of flavone-6,8-C-di-glycoside,and characteristic neutral loss could be assigned to glycosyl substitution,for example,neutral losses of C_4H_8O_4( 120),C_3H_6O_3( 90),C_2H_4O_2( 60) for glucoside substitution while neutral losses of C_4H_8O_3(104),C_3H_6O_2( 74),C_2H_4O( 44) for rhamnoside substitution. Furthermore,only one H_2O loss from mother ion( [M-H]-) was observed for 1 & 2 in ESI(-)-MS while five to six H2 O loss from mother ion( [M+H]+) was observed for 1 & 2 in ESI( +)-MS to produce a family of ions by subsequent loss of H_2O,which could be applied for glucosyl difference. The flavone-6,8-C-di-glycosides in both ESI( +)-MS and ESI(-)-MS showed the cleavage similarity at sugar substitutions. However,there were much more differences by the fragmentation pathways and neutral losses between ESI( +)-MS and ESI(-)-MS as following,hyperconjugation ions by subsequent loss of H_2O from precursor ions of flavone-6,8-C-di-glycosides in ESI( +)-MS were not observed in ESI(-)-MS; the subsequent neutral loss of CH_2O in ESI( +)-MS were rarely observed in ESI(-)-MS; the loss of CO only happen at C-ring of flavone ESI( +)-MS other than glycosyl position in ESI(-)-MS; the C4-chain neutral loss of flavone-6,8-C-di-glycosides happened at 8-C-glycosyl position other than at 6-C-glycosyl position. The above cleavage rules and diagnostic ions of ESI( +)-MS were successfully applied for the structure identification of 4 flavone-6 C,8 C-diglycosides from the stem extract of Dendrobium officinale as vicenin Ⅱ,vicenin Ⅰ,isoschaftoside,schaftoside as well as one flavone-O-glysoside named rutin,which were supported by ESI(-)-MS data as well.
Flavones/chemistry* ; Glycosides/chemistry* ; Ions ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

The quality of traditional Chinese medicine affects the clinical efficacy and the market research at home or abroad, which is closely related to the standardization of production. At present, Chinese market still exist in drug quality and nonstandard production phenomenon. In addition to the existing GMP production standards, it is still necessary to ensure the authenticity and reliability of traditional Chinese medicine by means of retrospect. Based on the Xinshenghua granule, starting from the authenticity of the whole process of production, this study designs and constructs the traditional Chinese medicine traceability system which is equipped with the Internet platform by using two-dimensional code as a trace tool. By making authentic record of the production process and quality transfer, it is convenient for consumers to know the drug information. The production traceability system provides guarantee for the standardization of traditional Chinese medicine development, in order to obtain the production source，the testing quality, whereabouts and responsibility.

In order to explore the compatible principles of Xiebai decoction family, formulae from ancient and modern Xiebai decoction family were collected and sorted in this study. The compatible characteristics, core herbs, as well as the relativity of herbs nature in Xiebai decoction family were analyzed based on scale free network and other data-mining methods such as association rules, clustering analysis and correspondence analysis. The scale free network results showed that in Xiebai decoction family, Mori Cortex-Lycii Cortex-Glycyrrhizae Radix et Rhizoma was used as the core compatible group and formed the complicated compatible network with other additional herbs; association rules results showed that the core herbs in such formulae included Mori Cortex, Lycii Cortex, Glycyrrhizae Radix et Rhizoma, scutellaria root, Platycodon root, Anemarrhena, and almond, which formed corresponding herbal pairs and compatibility; clustering analysis showed that Mori Cortex was the core herb in Xiebai decoction family, and Mori Cortex-Lycii Cortex-Glycyrrhizae Radix et Rhizoma was its main combination unit, which was always compatible with herbs of clearing heat, reducing phlegm, supplementing Qi and nourishing Yin to form the series prescriptions. The results indicated that the core compatibility features of Xiebai decoction family were clearing heat in lung and relieving cough and asthma, providing a basis for the clinical application of Xiebai decoction family.

OBJECTIVETo establish questionnaire scaling and reliability and examine the clinical and psychometric validity of the quality of life assessment based on Traditional Chinese Medicine for advanced gastric cancer (QLASTCM-Ga).

METHODSThe QLASTCM-Ga was developed based on programmed decision procedures with multiple nominal and focus group discussions, in-depth interview, pretesting and quantitative statistical procedures. The questionnaire was administered to 240 patients diagnosed with advanced gastric cancer before and after treatment. Structured group methods were employed to establish a general and a specifific module respectively. The psychometric properties of the scale were evaluated with respect to validity, reliability and responsiveness.

RESULTSThe three identified scales of the QLASTCM-Ga and the total score demonstrated good psychometric properties. Test-retest reliability of the total scale and all domains ranged from 0.90 to 0.94, and internal consistency ranged from 0.86 to 0.93. Correlation and factor analysis demonstrated good construct validity. Signifificant difference in the subscales and the total score were found among groups differing in traditional Chinese medicine syndrome, supporting the clinical sensitivity of the QLASTCM-Ga. Statistically signifificant changes were found for each scale and the total score. Responsiveness was also good.

CONCLUSIONSThe QLASTCM-Ga demonstrates good psychometric and clinical validity to assess quality of life in patients with advanced gastric cancer undergoing traditional Chinese medicine therapy. This study is an important fifirst step for future research in this area.

Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Neoplasm Staging ; Psychometrics ; methods ; Quality of Life ; Reproducibility of Results ; Stomach Neoplasms ; pathology ; Syndrome

Spontaneous remission (SR) of leukemia is a rare event in clinic, which possibly correlated with severe infection and sepsis, but its exact mechanism has not been confirmed. Plasmacytoid dendritic cells (pDC) and myeloid dendritic cells (mDC) play a key role in innate and adaptive immunity respectively. A patient with severe infection of staphylococcus aureus acquired completely spontaneous remission (SR), moreover a increased number of pDC were observed, suggesting that bacteria-activated pDC may play an important role in SR. This study was purposed to explore if the bacteria can stimulate pDC successfully and get a functional pDC. Both pDC and mDC were isolated from freshly collected, leukocyte-rich buffy coats from healthy blood donor and leukemic patient with SR by using MACS and FACS. The pDC were cultured in RPMI 1640 medium and were stimulated with different kinds of bacteria and the expression of CD40, CD86 and HLA-DR on the cell surface was analyzed by flow cytometry. The cytokine (IFN-α, IL-12, IFN-γ, IL-2, IL-4, IL-10) production was measured by using ELISA kits. The results showed that the stimulation with staphylococcus aureus and pseudomonas aeruginosa resulted in the maturation of pDC, which secrete a large number of IFN-α and promote the differentiation of naive CD4⁺ T cells to Th1 cells. The activated pDC expressed high level of CD40 and CD86 and showed higher T cell stimulatory capacities. It is concluded that staphylococcus aureus and pseudomonas aeruginosa can activate pDC, the activated pDC secrete high quantity of IFN-α. This result suggests that bacteria stimulated pDC may play a key role in SR of leukemia following severe infections.
CD4-Positive T-Lymphocytes ; Dendritic Cells ; immunology ; microbiology ; Humans ; Interferon-alpha ; Interleukin-10 ; Interleukin-12 ; Interleukin-2 ; Interleukin-4 ; Leukemia ; diagnosis ; immunology ; microbiology ; Remission, Spontaneous ; Staphylococcus aureus

This study was purposed to investigate the effect of high-dose dexamethasone (DXM) on function and Toll like receptor 9 (TLR-9) expression of plasmacytoid dendritic cells (pDC) in peripheral blood of patients with immune thrombocytopenic purpura (ITP). 15 newly diagnosed patients with ITP received high dose DXM at single daily doses of 40 mg for 4 consecutive days. The peripheral blood plasmacytoid dendritic cells from 13 remission patients and 15 normal controls were separated by immunomagnetic beads and then induced by CpG-OND2216. 24 h later, the levels of IFN-α, IL-6 and TNF-α in the supernatant were detected by enzyme linked immunosorbent assay (ELISA). The expression of TLR9 mRNA of pDC was detected by real-time quantitative PCR. The results indicated that the levels of IFN-α, IL-6 and TNF-α produced by pDC in ITP patients were significantly higher than those in normal controls (P < 0.05). After high dose DXM treatment, the levels of IFN-α, IL-6 and TNF-α decreased without significant difference compared with normal controls (P > 0.05). The expression of TLR9 mRNA in pDC of untreated patients was significantly higher than that in control group (P < 0.05), and significantly reduced after treatment without difference from that in control group (P > 0.05). It is concluded that pDC may play an important role in ITP by their TLR9 and secreted cytokines; dexamethasone may down regulate the expression of TLR9, inhibit pDC function, and thus play a therapeutic role.
Adolescent ; Adult ; Case-Control Studies ; Dendritic Cells ; immunology ; metabolism ; Dexamethasone ; administration & dosage ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Purpura, Thrombocytopenic, Idiopathic ; blood ; drug therapy ; immunology ; RNA, Messenger ; genetics ; Toll-Like Receptor 9 ; genetics ; metabolism ; Young Adult

OBJECTIVETo explore the changes of surface antigen and function of rituximab on dendritic cells derived from patients with Primary immune thrombocytopenia (ITP) to further understand the effective mechanism of immunotherapy.

METHODSThe peripheral blood mononuclear cells (PBMCs) were isolated from remission patients with ITP before and after low-dose rituximab infusion, and the PMNCs were stimulated for 5 days by rhGM-CSF and rhlL-4 in 5% CO2 air at 37°C incubator. Then all of DCs were cultured with TNF-α for 48 hours. The morphology of DCs was monitored under inverted microscope daily, and the surface antigens of the DCs were analysed by flow cytometry, meanwhile the levels of IL-12p70 and TGF-β1 in supernatants were detected by ELISA, mix lymphocyte reaction was performed by MTT assay.

RESULTS(1) Rituximab-treated-DCs showed no obvious tree-like protruding compared with untreated-DCs. The former cells were small and most of nucleus were centric. (2) The expressions of HLA-DR, CD80, CD83 and CD86 on rituximab-treated-DCs \[56.37 ± 3.95)%, (36.41 ± 2.82)%, (30.45 ± 4.61)% and (41.98 ± 4.17)%, respectively\] were significantly lower than those untreated-DCs \[(73.71 ± 7.61)%, (55.14 ± 7.30)%, (80.91 ± 7.09)% and (59.03 ± 3.43)%, respectively\](all P < 0.05), the concentration of IL-12p70 was significantly lower, \[(66.87 ± 4.29)% vs (50.17 ± 14.52)%\], while that of TGF-β1 \[(9.70 ± 0.31)%\] higher than the untreated-DCs \[(2.70 ± 0.36)%\] (P < 0.05). (3) The abilities to activate T cells proliferation of rituximab-treated-DCs reduced compared with untreated-DCs.

CONCLUSIONThe surface antigen of ITP-DCs and the concentration of IL-12p70 reduced after the low-dose rituximab infusion. The abilities to activate T cells proliferation reduced while the concentration of TGF-β1 increased. Rituximab may achieve its therapeutic effect on ITP by downregulating the immunoreactivity of DCs.

Antibodies, Monoclonal, Murine-Derived ; administration & dosage ; therapeutic use ; Cell Proliferation ; Cells, Cultured ; Dendritic Cells ; cytology ; metabolism ; secretion ; Female ; Humans ; Interleukin-12 ; metabolism ; Lymphocyte Activation ; Male ; Rituximab ; T-Lymphocytes ; immunology ; Thrombocytopenia ; drug therapy ; immunology ; metabolism ; Transforming Growth Factor beta1 ; metabolism