The Construction of ITP Diagnostic Modeling Based on the Expressions of Hub Genes Associated with M1 Polarization of Macrophages.

Purpose: Primary immune thrombocytopenia (ITP) is an immune disease with a diagnosis of exclusion, since no validated biomarkers have been identified. In this study, we explored biomarkers associated with the development of ITP from an immune perspective to inform the clinical diagnosis. Patients and Methods: Differentially expressed genes (DEGs) between normal and ITP samples were analyzed using limma package. Random forest algorithm and LASSO regression were further used to screen for DEGs associated with ITP. The expression of these hub genes was validated by PCR. The relationship between DEGs and immunity was explored by enrichment analysis. Immune cell infiltration in ITP was analyzed by CIBERSORT and ssGSEA, and the relationship between DEGs and infiltrating immune cells was analyzed by Spearman's rank correlation analysis. Finally, a diagnostic model related to DEGs was constructed by the neural network, and its efficiency was detected by the ROC curve. Results: After screening the GEO database and validation by PCR analysis, The expression of CTH and TAF8 were higher and while OSBP2 expression was lower in ITP patients compared to normal subjects (P<0.05). GO enrichment analysis showed that these DEGs were associated with inflammatory immune-related diseases, and KEGG analysis showed that they mainly regulated signaling pathways such as JAK-STAT. CIBERSORT and ssGSEA analyses showed that these DEGs were mainly associated with macrophage M1 polarization. The expression of CTH and TAF8 were positively correlated with M1 expression, while OSBP2 was negatively correlated with M1 expression. The ROC curve showed high accuracy of the neural network model [AUC= 0.939, 95% CI (0.8-1)]. Conclusion: Our results suggest that CTH, TAF8, and OSBP2 can be used as effective diagnostic biomarkers of ITP.

Enhancing Hole Density and Suppressing Recombination Centers through Illumination in Kesterite Thin Film Solar Cells.

Enhancing carrier density and increasing carrier lifetime are critical for the good performance of thin film solar cells. We apply illumination during the growth of kesterite Cu2ZnSnS4 (CZTS) to enhance hole density and suppress defects of nonradiative electron-hole recombination centers simultaneously. To examine the effect of the injected carriers generated by illumination, we first extend the scheme of detailed balance equations relating free carriers and defects beyond thermal equilibrium conditions by developing an extended Fermi level (EF') to characterize a homogeneous semiconductor with non-equilibrium carriers. On the basis of this scheme, we find that illumination can promote the formation of carrier-providing defects and suppress the formation of carrier-compensating defects. Then, we demonstrate that applying proper illumination during the growth of CZTS will help achieve a higher hole density and simultaneously suppress the formation of the SnZn antisite significantly, which are beneficial for the performance of CZTS solar cells.

Oral Arsenic-Containing Qinghuang Powder: A Potential Drug for Myelodysplastic Syndromes.

Qinghuang Powder (QHP), an oral arsenic, has become an effective drug in the treatment of myelodysplastic syndromes (MDS) in Xiyuan Hospital, China Academy of Chinese Medical Sciences for many years, and the action mechanism of the compound or active ingredient As2S2 of QHP has been elucidated. Considering the relatively safety, chemotherapy-free and convenient oral profile, QHP is widely used in the clinical treatment for MDS patients, especially for elderly patients. In this review, the authors document the efficacy and safety of oral arsenic-containing compound QHP in the treatment of MDS, with a special focus on the association of efficacy of QHP with the cytogenetics, prognostic risk, DNA methylation, gene mutation, blood arsenic concentration, mechanism of action of As2S2 and the countermeasures against adverse reactions of gastrointestinal tract.

[Expression of MicroRNAs in Peripheral Blood of Patients with Primary Immune Thrombocytopenia and Its Correlation with the Imbalance of Th1/Th2 Cell].

OBJECTIVE: To investigate the expressions of microRNAs in peripheral blood of patients with primary immune thrombocytopenia(ITP) and its correlation with the imbalance of Th1/Th2 cells. METHODS: Thirty patients with ITP (ITP group) and 15 healthy people (control group) were enrolled．Real-time polymerase chain reaction (RT-PCR) was used to detect the expressions of six miRNAs (miR-107,miR-205-5p,miR-138-5p,miR-326,miR-1827,miR-185-5p) and Th1-specific transcription factor T-bet mRNA and Th2-specific transcription factor GATA-3 mRNA in the peripheral blood of the two groups. Th1 and Th2 cells were detected by flow cytometry. The expressions of Th1-cytokines TNF-α and IFN-γ and Th2-cytokines IL-4 and IL-10 were detected by AimPlex multiple immunoassays for Flow. The expression difference of miRNAs, mRNA, Th1, Th2 cells and cytokines of the two groups were compared, and the correlations of miRNAs to mRNA, Th1, Th2 cells and cytokines were analyzed in ITP group. RESULTS: The expressions of miRNAs（miR-107, miR-205-5p, miR-138-5p, miR-326, miR-1827, miR-185-5p）and Th2-specific transcription factor GATA-3 mRNA of the patients in ITP group were significantly decreased (P<0.05) as compared with those in control, while the expressions of Th1 cells and Th1-specific transcription factor T-bet mRNA and Th1-cytokines TNF-α were significantly increased (P<0.05), also for the ratios of T-bet mRNA/GATA-3 mRNA and Th1/Th2 cells were significantly increased (P<0.05). The relative expressions of miR-107, miR-205-5p, miR-138-5p in ITP patients were negatively correlated with Th2 cells (r=-0.411, r=-0.593, r=-0.403,P<0.05) and the relative expression of miR-1827 was negatively correlated with TNF-α (r=-0.390). CONCLUSION: The relative expressions of the six miRNAs in peripheral blood of patients with ITP are significantly decreased, which result in the increasing ratio of T-bet mRNA/GATA-3 mRNA, then lead to the imbalance of Th1/Th2.

Arsenic concentration in peripheral blood is correlated with efficacy of a Traditional Chinese Medicine regimen containing realgar for the treatment of myelodysplastic syndrome.

OBJECTIVE: To explore the relationship between the efficacy of realgar for the treatment of myelodysplastic syndromes with multilineage dysplasia (MDS-MLD) and arsenic concentration in the peripheral blood of patients. METHODS: In this prospective study, a total of 50 MDS-MLD patients were treated with traditional Chinese drugs containing realgar for 3 months in Xiyuan Hospital from March 2018 to January 2019. Routine blood examination as well as liver and kidney function were monitored before and after treatment. The concentration of arsenic in the peripheral blood was measured using an atomic fluorescence spectrometer after treatment. The correlation between clinical effect and arsenic concentration was analyzed by Spearman's method. RESULTS: The treatment response rate was 54%. Two patients (4% ) achieved complete remission, 50% (25 of 50) showed hematologic improvement, and 23 patients had stable disease (23% ). No disease progression was observed. Arsenic concentration in the peripheral blood ranged from 14.60 to 85.96 µg/L. Clinical efficacy was positively correlated with arsenic concentration (P < 0.05). The incidence of mild adverse reactions was 16%. CONCLUSION: A relatively high concentration of arsenic in the peripheral blood may improve the clinical efficacy of realgar in MDS-MLD patients.

Dimensionality-Inhibited Chemical Doping in Two-Dimensional Semiconductors: The Phosphorene and MoS2 from Charge-Correction Method.

Despite the great appeal of two-dimensional semiconductors for electronics and optoelectronics, to achieve the required charge carrier concentrations by means of chemical doping remains a challenge due to large defect ionization energies (IEs). Here, by decomposing the defect IEs into three parts based on ionization process, we propose a conceptual picture that the large defect IEs are caused by two effects of reduced dimensionality. While the quantum confinement effect makes the neutral single-electron point defect levels deep, the reduced screening effect leads to high energy cost for the electronic relaxation. The first-principles calculations for black phosphorus and MoS2 do demonstrate the general trend. Using BP monolayer either embedded into dielectric continuum or encapsulated between two hBN layers, we demonstrate the feasibility of increasing the screening to reduce the defect IEs. Our analysis is expected to help achieve effective carrier doping and open ways toward more extensive applications of 2D semiconductors.

Hypofractionated versus conventionally fractionated image-guided volumetric-modulated arc radiotherapy for localized prostate cancer: a phase II randomized trial from China.

PURPOSE: To determine the safety of hypofractionated imaging-guided (IG) volumetric-modulated arc radiotherapy (IG-VMAT; 70 Gy/28 fractions over 5.5 weeks) versus conventionally fractionated regimen (IG-VMAT; 80 Gy/40 fractions over 8 weeks) in Chinese patients with localized prostate cancer. METHOD: In this randomized non-comparative phase II trial, 92 patients with localized prostate cancer were assigned to receive either hypofractionated IG-VMAT (HFRT; 70 Gy/2.5Gy/28f) or conventionally fractionated IG-VMAT (CFRT; 80 Gy/2Gy/40f). Primary endpoint was grade 2 or higher late gastrointestinal (GI) and genitourinary (GU) toxicity at 2 years. The GI/GU toxicity and biochemical relapse-free survival (bRFS) were compared between the two treatment groups. RESULTS: Median follow-up was 26 months. The incidence of grade 2 or higher late GI/GU toxicity was low in both groups; the 5-year cumulative incidence of Radiation Therapy Oncology Group grade 2 or higher GI/GU toxicity at 2 years was 7.6% with HFRT versus 10.3% with CFRT (P = 0.707). Biochemical control was not significantly different between the two groups; the 2-year bRFS was 94.6% for HFRT versus 95.0% for CFRT (P = 0.704). CONCLUSION: Hypofractionated IG-VMAT appears to be equivalent to conventionally fractionated IG-VMAT in terms of toxicity in Chinese patients with localized prostate cancer.

Clinical Response to Traditional Chinese Herbs Containing Realgar (As2S2) is Related to DNA Methylation Patterns in Bone Marrow DNA from Patients with Myelodysplastic Syndrome with Multilineage Dysplasia.

PURPOSE: DNA methylation is known to play an important role in myelodysplastic syndrome (MDS). We previously showed that Chinese herbs (CHs) containing realgar (As2S2) were effective at treating MDS with multilineage dysplasia (MDS-MLD). We tested whether the response to CH treatment was related to changes in DNA methylation in MDS-MLD. PATIENTS AND METHODS: First, the Illumina methylation 850K array BeadChip assay was used to assess the pretreatment methylation status in bone marrow cells from eight MDS-MLD patients and 3 healthy donors. The eight MDS-MLD patients were then treated with CHs for six months, the arsenic concentration was measured following treatment. The patients were subsequently divided into "effective" and "ineffective" treatment response groups and the DNA methylation patterns of the two groups were compared. Finally, the BeadChip data were validated by pyrosequencing. RESULTS: Five of the eight MDS-MLD patients showed hematological improvement (effective-treatment group), while three showed disease progression (ineffective-treatment group) (positive response rate: 62.5%). The arsenic concentrations in the patients ranged from 26.60 to 64.16 µg/L (median 48.4 µg/L) and were not significantly different between the two groups (p = 0.27). Compared with the healthy controls, three genes were hypomethylated and 110 were hypermethylated in the ineffective-treatment group. However, in the group showing hematological improvement, 102 genes were markedly hypomethylated and 87 hypermethylated. The effective-treatment group had a higher proportion of hypomethylated sites than the ineffective-treatment group (53.9% vs 2.6%, respectively; chi-square test) (p < 0.0001). Two hypermethylated and two hypomethylated genes were selected for validation by pyrosequencing (all p < 0.05). CONCLUSION: MDS-MLD patients may present different DNA methylation subtypes. CHs containing realgar may be effective for treating MDS-MLD patients with the hypomethylation subtype.

Radiomics of Multiparametric MRI to Predict Biochemical Recurrence of Localized Prostate Cancer After Radiation Therapy.

Background: To identify multiparametric magnetic resonance imaging (mp-MRI)-based radiomics features as prognostic factors in patients with localized prostate cancer after radiotherapy. Methods:From 2011 to 2016, a total of 91 consecutive patients with T1-4N0M0 prostate cancer were identified and divided into two cohorts for an adaptive boosting (Adaboost) model (training cohort: n = 73; test cohort: n = 18). All patients were treated with neoadjuvant endocrine therapy followed by radiotherapy. The optimal feature set, identified through an Inception-Resnet v2 network, consisted of a combination of T1, T2, and diffusion-weighted imaging (DWI) MR series. Through a Wilcoxon sign rank test, a total of 45 distinct signatures were extracted from 1,536 radiomics features and used in our Adaboost model. Results:Among 91 patients, 29 (32%) were classified as biochemical recurrence (BCR) and 62 (68%) as non-BCR. Once trained, the model demonstrated a predictive classification accuracy of 50.0 and 86.1% respectively for BCR and non-BCR groups on our test samples. The overall classification accuracy of the test cohort was 74.1%. The highest classification accuracy was 77.8% between three-fold cross-validation. The areas under the curve (AUC) of receiver operating characteristic curve (ROC) indices for the training and test cohorts were 0.99 and 0.73, respectively. Conclusion:The potential of multiparametric MRI-based radiomics to predict the BCR of localized prostate cancer patients was demonstrated in this manuscript. This analysis provided additional prognostic factors based on routine MR images and holds the potential to contribute to precision medicine and inform treatment management.

Arsenic Disulfide Promoted Hypomethylation by Increasing DNA Methyltransferases Expression in Myelodysplastic Syndrome.

BACKGROUND: Previous studies have shown that DNA methylation plays a significant role in myelodysplastic syndrome (MDS). In addition to hypermethylation, aberrant hypomethylation can result in the transcriptional activation of oncogenes in cancer, including MDS. Therefore, drugs targeting DNA hypomethylation are needed for the treatment of MDS. This study aimed to investigate whether As2S2 promoted hypomethylation by increasing DNA methyltransferases (DNMTs) expression in MDS. PATIENTS AND METHODS: Ten bone marrow samples from MDS patients and 3 healthy donors were obtained for the examination of the DNA methylation with a Human Methylation 850K BeadChip. The mRNA expressions for the DNMTs in the ten MDS patients and 3 controls were compared by Q-PCR. Then, the MDS cell line SKM-1 was treated with As2S2. After 2 days of treatment, Human Methylation 850K BeadChip was applied to analyze the changes of gene methylation status in the cells. Q-PCR and Western blot were taken to test the changes of mRNA and protein expressions for DNMTs in SKM-1 cells after treatment. RESULTS: Five hundred ninety-two abnormally hypomethylated genes were found in MDS patients compared to those in controls by Human Methylation 850K. The mRNA expressions of DNMTs (DNMT1, DNMT3a and DNMT3b) in MDS patients were significantly lower than those in healthy individuals. The IC50 value of As2S2 for SKM-1 cells was 4.97 µmol/L.Treatment with As2S2 at 2 µmoL/L resulted in significant alterations in the methylation levels at 1718 sites in SKM-1 cells compared to those in the controls. Hypermethylation was observed in 1625 sites (94.58%), corresponding to 975 genes, compared to those in the controls. Finally, the expression levels of DNMTs (DNMT1, DNMT3a, and DNMT3b) significantly increased in SKM-1 cells treated with As2S2 at 2 µmoL/L and 4 µmoL/L. CONCLUSION: These data show a potential clinical application of As2S2 as an innovative hypermethylation agent in MDS.

Traditional Chinese Medicine Containing Arsenic Treated MDS Patients Effectively through Regulating Aberrant Hypomethylation.

Aberrant hypermethylation and hypomethylation both play important roles in myelodysplastic syndrome (MDS). Hypomethylating agents targeting hypermethylation have been employed for the MDS treatment, but the treatment effect is limited. Novel drugs for DNA hypomethylation-targeted therapy may be needed to improve clinic efficacy for the treatment of MDS. Chinese medicine (CM) herbs have been used to treat MDS for many years in our hospital. However, the long-term treatment effect and mechanism remain unclear. In this study, all 135 patients received CM treatment for at least 36 months. The response rates for CM treatment were 81.53% (106/130) for hematological improvement in 130 MDS-RCMD patients and 80% (4/5) for bone marrow CR in 5 MDS-RAEB patients, respectively. The Human Methylation 850K BeadChip showed that 115 genes (50.88%) were aberrantly hypomethylated in 5 MDS patients compared with 3 healthy individuals. GO-analysis showed that these hypomethylated genes participated in many cancer-related biological functions and pathways. Furthermore, 60 genes were hypermethylated and the protein expression level of DNMT1 was significantly increased in the 5 MDS patients after 6 months of CM treatment. Our study suggests that CM can improve aberrant hypomethylation by increasing DNMT1 expression in MDS. The data support the clinical application of CM herbs containing arsenic as an innovative hypermethylation-inducing regimen for the treatment of MDS.

Arsenic-Containing Qinghuang Powder () is an Alternative Treatment for Elderly Acute Myeloid Leukemia Patients Refusing Low-Intensity Chemotherapy.

OBJECTIVE: To analyze the overall survival (OS) of elderly acute myeloid leukemia (AML) patients treated with oral arsenic-containing Qinghuang Powder (, QHP) or low-intensity chemotherapy (LIC). METHODS: Forty-two elderly AML patients treated with intravenous or subcutaneous LIC (1 month for each course, at least 3 courses) or oral QHP (3 months for each course, at least 2 courses) were retrospectively analyzed from January 2015 to December 2017. The main endpoints of analysis were OS and 1-, 2-, 3-year OS rates of patients, respectively. And the adverse reactions induding bone marrow suppression, digestive tract discomfort and myocardia injury were observed. RESULTS: Out of 42 elderly AML patients, 22 received LIC treatment and 20 received QHP treatment, according to patients' preference. There was no significant difference on OS between LIC and QHP patients (13.0 months vs. 13.5 months, >0.05). There was no significant difference on OS rates between LIC and QHP groups at 1 year (59.1% vs. 70.0%), 2 years (13.6% vs. 15%), and 3 years (4.6% vs. 5.0%, all >0.05). Furthermore, there was no significant difference of OS on prognosis stratification of performance status > 2 (12 months vs. 12 months), age> 75 year-old (12.0 months vs. 12.5 months), hematopoietic stem cell transplant comorbidity index >2 (12 months vs. 13 months), poor cytogenetics (12 months vs. 8 months), and diagnosis of secondary AML (10 months vs. 14 months) between LIC and QHP patients (>0.05). CONCLUSION: QHP may be an alternative treatment for elderly AML patients refusing LIC therapy.

Relation of Blood Arsenic Concentration with Effect and Safety of Arsenic-Containing Qinghuang Powder () in Patients with Myelodysplastic Syndrome.

OBJECTIVE: To investigate the relation of blood arsenic concentration (BAC) with clinical effect and safety of arsenic-containing Qinghuang Powder (, QHP) in patients with myelodysplastic syndrome (MDS). METHODS: Totally 163 patients with MDS were orally treated with QHP for 2 courses of treatment, 3 months as 1 course. The BACs of patients were detected by atomic fluorescence spectrophotometry at 1, 3, and 6 months during the treatment, and the effective rate, hematological improvement and safety in patients after treatment with QHP were analyzed. RESULTS: After 2 courses of treatment, the total effective rate was 89.6% (146/163), with 31.3% (51/163) of hematological improvement and 58.3% (95/163) of stable disease. The hemoglobin increased from 73.48 ± 19.30 g/L to 80.39 ± 26.56 g/L (P<0.05), the absolute neutrophil count increased from 0.81 ± 0.48 × 109/L to 1.08 ± 0.62 × 109/L (P<0.05), and no significant changes were observed in platelet counts (P>0.05). Among 46 patients previously depended on blood transfusion, 28.3% (13/46) completely got rid of blood transfusion and 21.7% (10/46) reduced the volume of blood transfusion by more than 50% after treatment. The BACs were significantly increased in patients treated for 1 month with 32.17 ± 18.04 µ g/L (P<0.05), 3 months with 33.56 ± 15.28 µ g/L (P<0.05), and 6 months with 36.78 ± 11.92 µ g/L (P<0.05), respectively, as compared with those before treatment (4.08 ± 2.11 µ g/L). There were no significant differences of BACs among the patients treated for 1, 3 and 6 months (P>0.05). The adverse reactions of digestive tract during the treatment were mild abdominal pain and diarrhea in 14 cases (8.6%), and no patients discontinued the treatment. The BACs of patients with gastrointestinal adverse reactions were significantly lower than those without gastrointestinal adverse reactions (22.39 ± 10.38 vs. 37.89 ± 11.84, µ g/L, P<0.05). The BACs of patients with clinical effect were significantly higher than those failed to treatment (40.41 ± 11.69 vs. 23.84 ± 12.03, µ g/L, P<0.05). CONCLUSION: QHP was effective and safe in the treatment of patients with MDS and the effect was associated with BACs of patients.

[Level of Regulatory B Cells in Patients with Immune Thrombocytopenia and Its Clinical Significance].

OBJECTIVE: To investigate the role of regulatory B cells (Breg) in pathogenesis of immune thrombocytopenia(ITP) and its clinical significance. METHODS: A total of 40 ITP patients and 20 normal controls were enrolled in this study. The content of Breg, Th1, Th2, Th17 and Treg cells were detected by flow cytometry (FCM). The expression level of IL-10,TGF-ß, CD40 and CD40L was detected by AimPlex Flow High Throughput Screening Technology. RESULTS: The of Breg cells in ITP patients was significantly lower than that in normal controls (P<0.05)，the expression levels of IL-10,TGF-ß and CD40L in ITP patients were also significantly lower than those in normal controls (P<0.05). The contents of Th1 cells in ITP patients were significantly higher than that in normal controls (P<0.05), whereas the contents of Th2, Th17 and Treg cells in ITP patients were significantly lower than those in normal controls (P<0.05). CONCLUSION: The Breg cells may play an important role in the pathogenesis of ITP.

Effect of Qinghuang Powder () Combined with Bupi Yishen Decoction () in Treating Patients with Refractory Cytopenia with Multilineage Dysplasia through Regulating DNA Methylation.

OBJECTIVE: To explore the effect of Qinghuang Powder (QHP,()combined with Bupi Yishen Decoction (BPYS, ) on myelodysplastic syndromes (MDS) patients with refractory cytopenia with multilineage dysplasia (RCMD) and determine the change of DNA methylation in MDS-RCMD patients after the treatment of Chinese medicine formula. METHODS: All 308 MDS-RCMD patients were treated with QHP combined with BPYS for 2 months at least, absolute neutrophil count (ANC), hemoglobin (Hb), platelets (PLT), primitive bone marrow cells and chromosome karyotype were chosen as the main evaluation indexes to analyze the treatment effect according to criteria from the MDS International Working Group. Then 43 bone marrow samples from 15 MDS-RCMD patients and 28 healthy donors were obtained for the examination of DNA methylation. Gene Ontology (GO) and Pathway analysis were applied to analyze the methylation data. RESULTS: The overall MDS response rate to QHP was 61.68% (190/360) including hematologic improvement-neutrophil (HI-N) or hematologic improvement-erythroid (HI-E) or hematologic improvement-platelet (HI-P). Patients with anemia had a better response rate than patients with neutropenia or thrombocypenia (55.88% vs 31.54% or 55.88% vs. 36.9%). The DNA methylation microarray analysis disclosed that 4,257 hypermethylated genes were demethylated upon the treatment with QHP and BPYS. GO analysis and Pathway analysis showed that these demethylated genes were involved in a lot of tumor-related pathways and functions. CONCLUSIONS: QHP combined with BPYS could effectively treat MDS-RCMD patients through hematologic improvement (HI-N, HI-P or HI-E) and PLT and RBC transfusion independence due to the demethylation, thereby providing another choice for the treatment of patients with MDS-RCMD.

[Secretory Imbalance between Pro-inflammatory and Anti-inflammatory Cytokines in the Patients with Immune Thrombocytopenia].

OBJECTIVE: To analyze the imbalance of pro-inflammatory and anti-inflammatory cytokines in the patients of immune thrombocytopenia (ITP). METHODS: Thirty-five patients with ITP were enrolled in ITP group, while 28 healthy persons were included in control group. The expressions of IL-8, IL-17A, IL-22, TNF-α, IFN-γ, IL-4, CD40, CD40L, TGF-ß and IL-10 were detected by flow cytometry with aimPlex multiple immunoassay Flow. RESULTS: The expressions of pro-inflammatory factors IL-8, IL-17A, IL-22, IFN-γ and TNF-α in ITP group all were significantly higher than that in the control group (P<0.05), however the expressions of anti-inflammatory factors IL-4, CD40L, TGF-ß and IL-10 in ITP group all were significantly lower than that in the control group (P<0.05). The expression of CD40 was not significantly different between ITP group and control group (P>0.05). Expressions of TNF-α significantly related with platelet counts in both ITP group and control group (ITP group, r=0.64, P<0.05; control group, r=-0.41, P<0.05). However the expression of CD40, TGF-ß, CD40L, IL-8, IL-17A, IL-22, IL-10, IL-1ß, IFN-γ and IL-4 significantly did not relate with platelet counts in both ITP and control group. CONCLUSIONS: The secretory imbalance between pro-inflammatory and anti-inflammatory cytokines exists in the patients of ITP. The decrease of Plt regulated may be regulated by the abnormal expression of TNF-α.

Effect of Yiqi Tongyang Decoction () on blood T cell subsets in patients with chronic immune thrombocytopenia.

OBJECTIVE: To measure the proportions of blood T cell subsets, Th1, Th2, Th17, Th22, and Treg cells, and other parameters in patients with chronic immune thrombocytopenia (CITP) before and after treatment with Yiqi Tongyang Decoction (, YTD) to explore T cell status of patients with CITP, and to defifine the mechanism of action of YTD. METHODS: The changes in peripheral blood T lymphocyte subsets, and those of Th1, Th2, Th17, Th22, and Treg cells in 30 patients with CITP (22 females and 8 males) were analyzed using multiparametric flflow cytometry before and after treatment with YTD for 6 months, and 26 healthy volunteers (14 males and 12 females) acted as a control. T-box expressed in T-cells (T-bet) and GATA binding protein 3 (GATA-3) mRNA levels in patients and controls were analyzed using real-time reverse transcription-polymerase chain reaction. RESULTS: The proportions of Th1, Th17, Th22, Th1/Th2, and Th17/Treg cells increased in the peripheral blood of patients with CITP compared to those in controls before YTD therapy (P<0.05). Th1 cell numbers and the Th1/Th2 ratio fell in the treated patients with CITP to approximate the values of the control group (P>0.05). Th17 cell numbers and the Th17/Treg ratio also decreased in the treatment group (P<0.05), but not to the levels of the controls. The number of Treg cells in the peripheral blood of patients with CITP before treatment was lower than that in the control group (P<0.05), but increased after YTD treatment P<0.05), but not to the level of controls. T-bet and GATA-3 mRNA levels in peripheral blood were initially higher in patients before treatment than controls (P<0.05), but decreased after YTD therapy (P<0.05). CONCLUSIONS: Imbalances in T lymphocyte levels, particularly those of Th1/Th2 and Th17/Treg cells, play important roles in the pathogenesis of CITP. YTD effificiently regulated the dynamics of Th1/Th2 and Th17/Treg equilibria.

[Effects of long-term fertilization on organic nitrogen fractions in aquic brown soil]. / 长期施肥对潮棕壤有机氮组分的影响.

The purpose of present research was to investigate how different fertilization regimes altered soil organic nitrogen fractions and their inter-annual dynamics based on a series of long-term experiment (initiated at 1990), including: CK (non-fertilization); M (recycled pig manure); NPK (chemical fertilizer NPK); NPK + M (recycled pig manure with chemical fertilizer NPK). The results showed that soil organic nitrogen components under the different fertilization treatments presented contrastive patterns from the establishment the experiments to 2015. Generally, acid hydrolysable organic nitrogen content increased year by year. The amino acid nitrogen content under CK and NPK treatments consistently declined, although amino acid nitrogen for M and NPK+M treatments showed a increasing trend. These phenomena were probably ascribed to the utilization of soil amino acids by microbes. From 1990 to 2015, NPK treatment substantially elevated the content of acid-released ammonium nitrogen by 31.1% compared with CK (mean value across the experiment), and for the treatments using organic manure (M and NPK+M), the contents of all fractions of soil organic nitrogen increased. Notably, the increase magnitudes for NPK+M were more dramatic than those of M. These results demonstrated that combined use of organic and inorganic fertilizers could more effectively elevate soil organic nitrogen, subsequently helping to improve the capacity of soil nitrogen supply and enhance the soil fertility.

Dosimetric and Clinical Outcomes With Intensity Modulated Radiation Therapy After Chemotherapy for Patients With Early-Stage Diffuse Large B-cell Lymphoma of Waldeyer Ring.

PURPOSE: To assess the dosimetric benefit, prognosis, and toxicity of intensity modulated radiation therapy (IMRT) for early-stage, diffuse large B-cell lymphoma of Waldeyer ring (WR-DLBCL). METHODS AND MATERIALS: Sixty-one patients with early-stage WR-DLBCL who received chemotherapy followed by IMRT were retrospectively reviewed. Dosimetric parameters for the target volume and critical normal structures were evaluated, and survival was calculated. Linear regression analysis was used to assess the effect of the mean dose (Dmean) to the parotid glands on xerostomia. RESULTS: The median conformity index and homogeneity index of the planning target volume (PTV) were 0.83 and 0.90, respectively, demonstrating very good coverage of the target volume. The mean dose to the parotid glands was 24.9 Gy. The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) were 94.7%, 93.1%, and 98.3%, respectively. Early and late toxicities were mild, and no patient experienced late grade ≥3 toxicities. The Dmean to the parotid glands had a linear correlation with late grade ≥2 xerostomia. CONCLUSIONS: IMRT after chemotherapy can provide excellent dose conformity and achieve favorable survival and LRC with mild toxicities in patients with early-stage WR-DLBCL. Dose constraints for the parotid glands should be limited to <24 Gy for early-stage WR-DLBCL.

Panax quinquefolium saponin combined with dual antiplatelet drugs inhibits platelet adhesion to injured HUVECs via PI3K/AKT and COX pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax quinquefolium saponin (PQS) is the active component extracted from traditional Chinese medicine Panax quinquefolius L. and has been widely used as a supplement to dual antiplatelet drugs (DA) for treatment of coronary artery disease (CAD) for two decades; however, the efficacy of PQS combined with DA against platelet adhesion to endothelial cells (ECs), an essential step in thrombosis, remains unclear. AIM OF THE STUDY: To compare PQS combined with DA and DA alone in inhibiting platelet adhesion to injured human umbilical vein endothelial cells (HUVECs) and to explore the possible mechanisms focusing on PI3K/AKT, COX-2/6-keto-PGF1α, and COX-1/TXB2 pathways. METHODS: HUVECs injured by oxidized low-density lipoprotein (ox-LDL) were randomly allocated into control, model, DA, PQS+DA (P+DA), LY294002 (a PI3K inhibitor)+DA (L+DA), and LY294002+PQS+DA (LP+DA) groups. HUVEC apoptosis, platelet adhesion to injured HUVECs, and platelet CD62p expression were assayed by fluorescence activated cell sorting (FACS). The concentrations of 6-keto-PGF1α and TXB2 in the supernatant were measured by radioimmunoassay. Protein expression of phosphorylated-PI3K, PI3K, phosphorylated-AKT, AKT, COX-1, and COX-2 in both platelets and HUVECs was evaluated by western blot. RESULTS: Compared to DA alone, PQS combined with DA reduced platelet adhesion to HUVECs and HUVEC apoptosis more potently, increased the concentration of supernatant 6-keto-PGF1α and up-regulated phospho-AKT protein in HUVECs. LY294002 mitigated the effects of PQS on HUVEC apoptosis and platelet adhesion. CONCLUSIONS: These findings show that PQS as a powerful supplement to DA, attenuated HUVEC apoptosis and improved the DA-mediated reduction of platelet adhesion to injured HUVECs and the underlying mechanisms may be associated with PI3K/AKT and COX pathways in HUVECs and platelets. PQS might provide a new complementary approach to improve the prognosis of thrombotic diseases in future.