Objective To evaluate the clinical efficacy of navel application of Jianpi Hewei Adhesive Plaster combined with oral use of modified Sini Hewei Anshen Decoction in treating diabetic gastroparesis(DGP)accompanied by anxiety of liver-stomach disharmony type in type 2 diabetes patients.Methods One hundred patients with DGP accompanied by anxiety of liver-stomach disharmony type were randomly divided into a treatment group and a control group,with 50 patients in each group.The control group was given oral use of Mosapride Citrate Tablets orally,and the treatment group was given navel application of Jianpi Hewei Adhesive Plaster combined with oral use of modified Sini Hewei Anshen Decoction.The course of treatment for the two groups covered 4 weeks.The two groups were observed in the changes of the traditional Chinese medicine(TCM)syndrome scores,Gastroparesis Cardinal Symptom Index(GCSI)scores,Hamilton Anxiety Scale(HAMA)scores,gastric emptying time,and levels of fasting blood glucose(FBG),2-hour postprandial blood glucose(2hPG),glycated hemoglobin(HbA1c),plasma motilin(MOT),gastrin(GAS),and serum tumor necrosis factor alpha(TNF-α)and interleukin 6(IL-6)before and after the treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)During the trial,4 patients in the treatment group and 3 patients in the control group fell off,and eventually a total of 93 patients were included for the efficacy statistics,including 46 patients in the treatment group and 47 patients in the control group.(2)After 4 weeks of treatment,the total effective rate of the treatment group was 95.65%(44/46)and that of the control group was 76.60%(36/47).The intergroup comparison(tested by chi-square test)showed that the therapeutic effect of the treatment group was significantly superior to that of the control group(P＜0.01).(3)After treatment,the TCM syndrome scores(including epigastric and abdominal congestion,depression or irritability,and poor appetite)and GCSI scores in the two groups were decreased compared with those before treatment(P＜0.05)and the gastric emptying time was shortened compared with that before treatment(P＜0.05),and the effect of the treatment group on decreasing TCM syndrome scores and GCSI scores and on shortening the gastric emptying time were significantly superior to that of the control group(P＜0.01).(4)After treatment,the plasma MOT and GAS levels of the two groups were increased compared with those before treatment(P＜0.05),and the increase in the treatment group was significantly superior to that in the control group(P＜0.01).(5)After treatment,the levels of glucose metabolism indicators of FBG,2hPG,and HbA1c in the two groups were decreased compared with those before treatment(P＜0.05),but the differences of all glucose metabolism indicators between the two groups after treatment were not statistically significant(P＞0.05).(6)After treatment,the serum TNF-α and IL-6 levels in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease in the treatment group was significantly superior to that in the control group(P＜0.05).(7)After treatment,the total HAMA scores and the scores of mental anxiety factor and somatic anxiety factor of HAMA in the two groups were decreased compared with those before treatment(P＜0.05),and the effect on lowering the scores in the treatment group was significantly superior to that in the control group(P＜0.05).(8)During the treatment period,no significant adverse reactions occurred in the two groups of patients,which has high safety.Conclusion Navel application of Jianpi Hewei Adhesive Plaster combined with oral use of modified Sini Hewei Anshen Decoction exerts certain efficacy in treating DGP accompanied by anxiety of liver-stomach disharmony type.The therapy is effective on relieving clinical symptoms,enhancing gastric motility,inhibiting inflammatory response,and improving anxiety emotion and the quality of life of the patients.

Objective To observe the clinical efficacy of Yiqi Yangyin Jiangtang Prescription(mainly composed of Astragali Radix,Rehmanniae Radix,Imperatae Rhizoma,Ophiopogonis Radix,and Puerariae Lobatae Radix)combined with acupoint injection in the treatment of newly-diagnosed type 2 diabetes mellitus(T2DM).Methods One hundred patients with newly-diagnosed T2DM of qi-yin deficiency complicated with blood stasis type were randomly divided into a treatment group and a control group,with 50 patients in each group.The control group was given oral use of Metformin Hydrochloride Tablets,and the treatment group was given the granules of Yiqi Yangyin Jiangtang Prescription orally combined with acupoint injection at unilateral points of Zusanli(ST36),Shenshu(BL23)and Qihai(CV6)on the basis of treatment for the control group.The course of treatment lasted for 4 weeks.Before and after the treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,fasting plasma glucose(FPG),2-hour postprandial blood glucose(2hPG),glycated hemoglobin(HbA1c),total cholesterol(TC),triglyceride(TG),and serum levels of inflammatory factors of interleukin 6(IL-6),C-reactive protein(CRP),tumor necrosis factor α(TNF-α),as well as the hemorheology indicators of whole blood low-shear viscosity and whole blood high-shear viscosity.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)During the trial,5 cases fell off from the treatment group and 4 cases fell off from the control group,and a total of 91 patients were eventually included in the efficacy statistics,of which 45 cases were in the treatment group and 46 cases were in the control group.(2)After 4 weeks of treatment,the total effective rate of the treatment group was 93.33%(42/45),and that of the control group was 71.74%(33/46).The intergroup comparison(tested by chi-square test)showed that the therapeutic effect of the treatment group was significantly superior to that of the control group(P＜0.01).(3)After treatment,the scores of TCM symptoms of dry mouth and throat,frequent nocturia,shortness of breath and fatigue,hot flushes and night sweating as well as the total TCM syndrome scores in the two groups were significantly lower than those before the treatment(P＜0.05),and the reduction of the scores in the treatment group was significantly superior to that of the control group(P＜0.01).(4)After treatment,the levels of blood glucose and lipid indicators of FPG,2hPG,HbA1c,TC and TG of patients in the two groups were decreased compared with those before treatment(P＜0.05),and the decrease in the treatment group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(5)After treatment,the serum levels of inflammatory factors of IL-6,CRP,and TNF-α in the two groups were all lower than those before treatment(P＜0.01),and the reduction in the treatment group was significantly superior to that in the control group(P＜0.01).(6)After treatment,the levels of hemorheology indicators such as whole blood low-shear viscosity and high-shear viscosity in the two groups were all lower than those before treatment(P＜0.05),and the reduction in the treatment group was significantly superior to that in the control group(P＜0.05).(7)The incidence of adverse reactions in the treatment group was 8.89%(4/45),which was significantly lower than that of the control group(21.74%,10/46),and the difference was statistically significant(P＜0.01).Conclusion Yiqi Yangyin Jiangtang Prescription combined with acupoint injection exerts certain effect in treating patients with newly-diagnosed T2DM of qi-yin deficiency complicated with blood stasis syndrome type.The combined therapy can effectively alleviate the early clinical manifestations,decrease the levels of blood glucose,blood lipids,and inflammatory factors,and improve the hematological indicators and the quality of life of the patients.

Objective To establish a HPLC method for the simultaneous determination of artemisinin,arteannuin B,chrysosplenetin and chrysosplenol-D in the water extract of Artemisia annua L.Methods The analysis was performed on Agilent ZORBAX SB-C18(250 mm×4.6 mm,5 μm)column with a mobile phase of acetonitrile(A)-water(B)and the flow rate of 0.8 mL·min-1 in a gradient elution manner.The column temperature was 30℃.The injection volume was 10 μL,and the detection wavelength was 210 nm.Results Artemisinin,arteannuin B,chrysosplenetin and chrysosplenol-D were correlated well linearly with peak area in their respective ranges 1.608 8-16.088 μg(r=0.999 9),0.014 1-0.141 4 μg(r=1),0.185 1-1.850 9 μg(r=0.999 9),0.144 1-1.441 4 μg(r=0.999 9),the average recovery rate(n=6)were 102.44%,97.82%,95.07%,95.55%,and the RSD values were 1.12%,1.44%,1.29%,1.53%.Conclusion This method is convenient and accurate.It has good stability and repeatability,and can be used to simultaneously determine the content of artemisinin,arteannuin B,chrysosplenetin and chrysosplenol-D in the water extract of Artemisia annua L.

italic>Lonicera Linn. is the largest genus of family Caprifoliaceae, which has a long history and abundant resources in China. Due to its ornamental and medicinal properties, the species of Lonicera shows outstanding economic value. However, affected by the huge demand and high price stimulation, there is a serious mixing phenomenon on the market. In this study, high-throughput sequencing technology was used to analyze the analysis of L. angustifolia Wallich ex Candolle var. myrtillus (Hook. f. & Thomson) Q. E. Yang, L. myrtillus Hook. f. et Thoms. var. cyclophylla Rehd, L. szechuanica Batal and L. tangutica Maxim to sequence and assemble their chloroplast (CP) genomes, and to conduct structural comparisons and phylogenetic studies. The results showed that the chloroplast genomes of the four species showed a typical circular tetrad structure, with a total length of 154 608-163 413 bp and a total GC content of 37.93%-38.42%. A total of 128-129 genes were annotated, including 83-84 protein-coding genes, 8 rRNA genes, and 37 tRNA genes. A total of 53-68 SSRs and 133-745 long repeats were detected by chloroplast repeat structure analysis. Phylogenetic studies showed that 21 species of Lonicera medicinal plants could be significantly clustered into one branch, among which the relatives of L. angustifolia and L. szechuanica were close, and the kinship of L. myrtillus and L. tangutica was close. This study is the first comprehensive study of the chloroplast genome and phylogenetic relationship of Loicera species, and the experimental results provide a scientific basis for revealing the genetic information, species evolution and genetic diversity of Lonicera species.

Objective: To investigate the expression of programmed death protein-ligand 1 (PD-L1) in liver cancer stem-like cells (LCSLC) and its effect on the characteristics of tumor stem cells and tumor biological function, to explore the upstream signaling pathway regulating PD-L1 expression in LCSLC and the downstream molecular mechanism of PD-L1 regulating stem cell characteristics, also tumor biological functions. Methods: HepG2 was cultured by sphere-formating method to obtain LCSLC. The expressions of CD133 and other stemness markers were detected by flow cytometry, western blot and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the expressions of stemness markers and PD-L1. The biological functions of the LCSLC were tested by cell function assays, to confirm that the LCSLC has the characteristics of tumor stem cells. LCSLC was treated with cell signaling pathway inhibitors to identify relevant upstream signaling pathways mediating PD-L1 expression changes. The expression of PD-L1 in LCSLC was down regulated by small interfering RNA (siRNA), the expression of stem cell markers, tumor biological functions of LCSLC, and the changes of cell signaling pathways were detected. Results: Compared with HepG2 cells, the expression rate of CD133 in LCSLC was upregulated [(92.78±6.91)% and (1.40±1.77)%, P<0.001], the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were also higher than those in HepG2 cells (P<0.05), the number of sphere-formating cells increased on day 7 [(395.30±54.05) and (124.70±19.30), P=0.001], cell migration rate increased [(35.41±6.78)% and (10.89±4.34)%, P=0.006], the number of transmembrane cells increased [(75.77±10.85) and (20.00±7.94), P=0.002], the number of cloned cells increased [(120.00±29.51) and (62.67±16.77), P=0.043]. Cell cycle experiments showed that LCSLC had significantly more cells in the G(0)/G(1) phase than those in HepG2 [(54.89±3.27) and (32.36±1.50), P<0.001]. The tumor formation experiment of mice showed that the weight of transplanted tumor in LCSLC group was (1.32±0.17)g, the volume is (1 779.0±200.2) mm(3), were higher than those of HepG2 cell [(0.31±0.06)g and (645.6±154.9)mm(3), P<0.001]. The expression level of PD-L1 protein in LCSLC was 1.88±0.52 and mRNA expression level was 2.53±0.62, both of which were higher than those of HepG2 cells (P<0.05). The expression levels of phosphorylation signal transduction and transcription activation factor 3 (p-STAT3) and p-Akt in LCSLC were higher than those in HepG2 cells (P<0.05). After the expression of p-STAT3 and p-Akt was down-regulated by inhibitor treatment, the expression of PD-L1 was also down-regulated (P<0.05). In contrast, the expression level of phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) in LCSLC was lower than that in HepG2 cells (P<0.01), there was no significant change in PD-L1 expression after down-regulated by inhibitor treatment (P>0.05). After the expression of PD-L1 was knockdown by siRNA, the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were decreased compared with those of siRNA-negative control (NC) group (P<0.05). The number of sphere-formating cells decreased [(45.33±12.01) and (282.00±29.21), P<0.001], the cell migration rate was lower than that in siRNA-NC group [(20.86±2.74)% and (46.73±15.43)%, P=0.046], the number of transmembrane cells decreased [(39.67±1.53) and (102.70±11.59), P=0.001], the number of cloned cells decreased [(57.67±14.57) and (120.70±15.04), P=0.007], the number of cells in G(0)/G(1) phase decreased [(37.68±2.51) and (57.27±0.92), P<0.001], the number of cells in S phase was more than that in siRNA-NC group [(30.78±0.52) and (15.52±0.83), P<0.001]. Tumor formation in mice showed that the tumor weight of shRNA-PD-L1 group was (0.47±0.12)g, the volume is (761.3±221.4)mm(3), were lower than those of shRNA-NC group [(1.57±0.45)g and (1 829.0±218.3)mm(3), P<0.001]. Meanwhile, the expression levels of p-STAT3 and p-Akt in siRNA-PD-L1 group were decreased (P<0.05), while the expression levels of p-ERK1/2 and β-catenin did not change significantly (P>0.05). Conclusion: Elevated PD-L1 expression in CD133(+) LCSLC is crucial to maintain stemness and promotes the tumor biological function of LCSLC.
Humans ; Animals ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; B7-H1 Antigen/metabolism* ; Ligands ; Liver Neoplasms/pathology* ; RNA, Small Interfering/metabolism* ; Neoplastic Stem Cells/physiology* ; Cell Line, Tumor ; Cell Proliferation

Objective: To explore the relationship between nutrient-related dietary pattern and mild cognitive impairment (MCI) in middle-aged and elderly people. Methods: A total of 6 444 middle-aged and elderly people aged ≥55 years were selected in 2018 China Health and Nutrition Survey. MCI was evaluated by Mini-Mental State Examination, and the intakes of various foods were obtained by consecutive 3-day 24-hour dietary survey and weighing method. The intakes of various nutrients and total dietary energy were calculated based on the food composition table. Demographic and social information, lifestyle and health status of the respondents were obtained through questionnaire survey and physical measurements. In this study, vitamin C, vitamin E, zinc, iron, copper and selenium were selected as dependent variables. Nutrient-related dietary patterns were extracted by reduced rank regression method, and the relationship between dietary patterns and MCI was analyzed by multivariate logistic regression model. Results: Six dietary patterns were extracted in this study, and dietary pattern 1 with the highest explanatory degree was selected for subsequent analysis. Dietary pattern 1 was characterized by higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products and plant oil. Multivariate logistic regression analysis showed that the risk of MCI was lower in Q₄ dietary score group than in Q₁ dietary score group (OR=0.69, 95%CI: 0.49-0.98) in the 55-64 age group. In people with sleep duration of 8 hours per day, the risk of MCI was reduced in Q₂, Q₃ and Q₄ dietary score groups compared with the Q₁ dietary score group, with OR values of 0.68 (95%CI: 0.51-0.92), 0.67 (95%CI: 0.49-0.92) and 0.65 (95%CI: 0.45-0.92), respectively. Interaction analysis showed that the risk for MCI increased in those aged 65-74 years and ≥75 years compared with those aged 55-64 years in Q₁ dietary score group. However, the risk for MCI decreased in both age groups as dietary pattern scores increased. Compared with those with sleep duration less or more than 8 hours per day in Q₁ dietary score group, those with sleep duration of 8 hours per day in Q₂ and Q₃ dietary score groups had a reduced risk for MCI. Conclusion: Dietary patterns with higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products, and plant oil are negatively associated with MCI in people aged 55-64 years and those who slept 8 hours per day, and may reduce the risk of MCI with aging.
Aged ; Middle Aged ; Humans ; Feeding Behavior/psychology* ; Diet ; Cognitive Dysfunction/epidemiology* ; Nutrients ; Vegetables ; China/epidemiology*

Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male ; Humans ; Prostate-Specific Antigen ; Treatment Outcome ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Retrospective Studies

Dihydroflavonol 4-reductase (DFR) plays an essential role in the biosynthesis of anthocyanin and regulation of plant flower color. Based on the transcriptome data of Cistanche tubulosa (Schenk) Wight, a full-length cDNA sequence of CtDFR gene was cloned by reverse transcription-polymerase chain reaction (RT-PCR). CtDFR contains an open reading frame (ORF) of 1 263 bp which encodes 420 amino acids with a predicted molecular weight of 47.5 kDa. The sequence analysis showed that CtDFR contains a nicotinamide adenine dinucleotide phosphate (NADPH) binding domain and a specific substrate binding domain. The expression analysis indicated that CtDFR was highly expressed in red and purple flowers, and the relative expression levels were 4.04 and 19.37 times higher than those of white flowers, respectively. The recombinant CtDFR protein was expressed in E.coli BL21 (DE3) using vector pET-28a-CtDFR and was purified. In vitro enzyme activity analysis, CtDFR could reduce three types of dihydroflavonols including dihydrokaempferol, dihydroquercetin, and dihydromyricetin to leucopelargonidin, leucocyanidin and leucodelphinidin. Subcellular localization analysis showed that CtDFR was mainly localized in the cytoplasm. These results demonstrate that CtDFR plays an important role in regulation of flower color in C. tubulosa and make a valuable contribution for the further investigation on the regulation mechanism of C. tubulosa (Schenk) Wight flower color.

OBJECTIVE: Jiedu Recipe (JR), a Chinese herbal remedy, has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma (HCC). This work investigated the mechanism of JR in HCC treatment. METHODS: The chemical constituents of JR were detected using liquid chromatography-mass spectrometry. The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid (mRNA) microarray chip assay, followed by experimental validation in human HCC cells (SMMC-7721 and Huh7) in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo. HCC cell characteristics of proliferation, migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide, wound healing and Transwell assays, respectively. Image-iT™ Hypoxia Reagent was added to reveal hypoxic conditions. Stem cell sphere formation assay was used to detect the stemness. Epithelial-mesenchymal transition (EMT) markers like E-cadherin, vimentin and α-smooth muscle actin, and pluripotent transcription factors including nanog homeobox, octamer-binding transcription factor 4, and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction. Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/β-catenin pathway. RESULTS: According to network pharmacology and mRNA microarray chip analysis, JR may potentially act on hypoxia and inhibit the Wnt/β-catenin pathway. In vitro and in vivo experiments showed that JR significantly decreased hypoxia, and suppressed HCC cell features of proliferation, migration and invasion; furthermore, the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR. Results based on the co-administration of JR and an agonist (LiCl) or inhibitor (IWR-1-endo) verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/β-catenin pathway. CONCLUSION JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/β-catenin pathway under hypoxic conditions. Please cite this article as: Guo BJ, Ruan Y, Wang YJ, Xiao CL, Zhong ZP, Cheng BB, Du J, Li B, Gu W, Yin ZF. Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/β-catenin pathway under hypoxia. J Integr Med. 2023; 21(5): 474-486.
Animals ; Mice ; Humans ; Carcinoma, Hepatocellular/genetics* ; beta Catenin/pharmacology* ; Liver Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; RNA, Messenger/therapeutic use* ; Cell Line, Tumor ; Cell Proliferation ; Cell Movement ; Gene Expression Regulation, Neoplastic

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*