OBJECTIVE To analyze the chemical constituents of Heihuang Chizhu Granules and the blood composition of rats af-ter administration by UPLC-Q-TOF-MS/MS.METHODS A Waters ACQUITY UPLC HSS T3 column(3 mm×100 mm,1.8 μm)was eluted with acetonitrile-0.1%formic acid as mobile phase,and the data were collected in electrospray ion source positive and neg-ative ion mode and then identified with the reference retention time,precise molecular weight,secondary fragment ions,and references to relevant literature.RESULTS A total of 104 chemical components were identified from Heihuang Chizhu Granules,including 26 flavonoids,24 organic acids,14 triterpenoids,8 terpenoids,7 phenylpropanoids,11 monoglycosides,and 14 other components(phe-nols,alkaloids,etc.).On this basis,39 blood-entering components were identified in the plasma of rats administered via gavage,in-cluding 28 prototypes and 11 metabolites.CONCLUSION The chemical constituents of Heihuang Chizhu Granules and the compo-nents entering the blood of rats are analyzed and identified for the first time in this study,and the results provide a scientific basis for the basic research of Heihuang Chizhu Granules and the establishment of process quality control standards.

OBJECTIVE To optimize the molding process of Xiebai Granules(XG)using the Box-Behnken design-response surface method combined with the BP neural network method,and to evaluate the consistency of particle quality between different bat-ches by establishing physical fingerprint.METHODS Dry paste powder was used as the main drug,dry granulation was adopted,and the forming rate,dissolution rate,moisture absorption rate and angle of repose of the granules were used as evaluation indexes,the ex-cipients dextrin,maltodextrin and lactose of the particles,were screened by single factor test combined with simplex-lattice design and entropy weight method,and the optimal excipient ratio was selected.The entropy weight method combined with the Box-Behnken de-sign-response surface method and the BP neural network algorithm were used to optimize the process parameters,and the process veri-fication was carried out.The physical fingerprint was used to comprehensively characterize the bulk density(Da),hygroscopicity(H),moisture(HR),tap density(Dc),angle of repose(α),Hausner ratio(IH),relative uniformity index(Iθ),Carr index(IC),and in-terparticle pore number(Ie),and the consistency of particle quality in different batches was evaluated.RESULTS The optimal ratio of excipients was dextrin 15%,maltodextrin 48%,and lactose 37%.The optimal process parameters were conveying speed 95 r·min-1,pressure wheel speed 4 r·min-1 and hydraulic pressure 7 MPa.The similarity of the physical fingerprints of the five bat-ches of XG was greater than 0.98.CONCLUSION The optimized molding process of XG is stable and feasible,and the quality of different batches of XG is stable,which can provide a reference for the development and industrial scale-up production of XG.

OBJECTIVE To optimize the molding process of Xiebai Granules(XG)using the Box-Behnken design-response surface method combined with the BP neural network method,and to evaluate the consistency of particle quality between different bat-ches by establishing physical fingerprint.METHODS Dry paste powder was used as the main drug,dry granulation was adopted,and the forming rate,dissolution rate,moisture absorption rate and angle of repose of the granules were used as evaluation indexes,the ex-cipients dextrin,maltodextrin and lactose of the particles,were screened by single factor test combined with simplex-lattice design and entropy weight method,and the optimal excipient ratio was selected.The entropy weight method combined with the Box-Behnken de-sign-response surface method and the BP neural network algorithm were used to optimize the process parameters,and the process veri-fication was carried out.The physical fingerprint was used to comprehensively characterize the bulk density(Da),hygroscopicity(H),moisture(HR),tap density(Dc),angle of repose(α),Hausner ratio(IH),relative uniformity index(Iθ),Carr index(IC),and in-terparticle pore number(Ie),and the consistency of particle quality in different batches was evaluated.RESULTS The optimal ratio of excipients was dextrin 15%,maltodextrin 48%,and lactose 37%.The optimal process parameters were conveying speed 95 r·min-1,pressure wheel speed 4 r·min-1 and hydraulic pressure 7 MPa.The similarity of the physical fingerprints of the five bat-ches of XG was greater than 0.98.CONCLUSION The optimized molding process of XG is stable and feasible,and the quality of different batches of XG is stable,which can provide a reference for the development and industrial scale-up production of XG.

OBJECTIVE To analyze the chemical constituents of Heihuang Chizhu Granules and the blood composition of rats af-ter administration by UPLC-Q-TOF-MS/MS.METHODS A Waters ACQUITY UPLC HSS T3 column(3 mm×100 mm,1.8 μm)was eluted with acetonitrile-0.1%formic acid as mobile phase,and the data were collected in electrospray ion source positive and neg-ative ion mode and then identified with the reference retention time,precise molecular weight,secondary fragment ions,and references to relevant literature.RESULTS A total of 104 chemical components were identified from Heihuang Chizhu Granules,including 26 flavonoids,24 organic acids,14 triterpenoids,8 terpenoids,7 phenylpropanoids,11 monoglycosides,and 14 other components(phe-nols,alkaloids,etc.).On this basis,39 blood-entering components were identified in the plasma of rats administered via gavage,in-cluding 28 prototypes and 11 metabolites.CONCLUSION The chemical constituents of Heihuang Chizhu Granules and the compo-nents entering the blood of rats are analyzed and identified for the first time in this study,and the results provide a scientific basis for the basic research of Heihuang Chizhu Granules and the establishment of process quality control standards.

Itaconate is a pivotal intermediate metabolite in the tricarboxylic acid (TCA) cycle of immune cells. It is produced by decarboxylation of cis-aconitic acid under the catalysis of aconitate decarboxylase 1 (ACOD1), which is encoded by the immune response gene 1 (IRG1). Itaconate has become a focal point of research on immunometabolism. Studies have demonstrated that itaconate plays a crucial role in diseases by regulating inflammation, remodeling cell metabolism, and participating in epigenetic regulation. This paper reviewed the research progress in itaconnate from its chemical structure, regulatory effects on different diseases, and mechanisms, proposes the future research directions, aiming to provide a theoretical basis for the development of itaconate-related drugs.
Humans ; Succinates/metabolism* ; Carboxy-Lyases/genetics* ; Inflammation/metabolism* ; Citric Acid Cycle ; Animals ; Epigenesis, Genetic ; Neoplasms/immunology*

Ten-eleven translocation 1 (TET1) protein is an alpha-ketoglutaric acid (α-KG) and Fe²⁺-dependent dioxygenase. It plays a role in the active demethylation of DNA by hydroxylation of 5-methyl-cytosine (5-mC) to 5-hydroxymethyl-cytosine (5-hmC). Ten-eleven translocation 1 (TET1) protein is involved in maintaining genome methylation homeostasis and epigenetic regulation. Abnormally expressed TET1 and 5-mC oxidative derivatives have become potential markers in various biological and pathological processes and a research focus in the fields of embryonic development and malignant tumors. This paper introduces the structure and demethylation mechanism of TET1, reviews the research status of epigenetic regulation by TET1 in embryonic development, immune responses, stem cell regulation, cancer progression, and nervous system development, and briefs the upstream regulatory mechanism of TET1, hoping to provide new inspirations for further research in related fields.
Proto-Oncogene Proteins/genetics* ; Epigenesis, Genetic ; Humans ; DNA-Binding Proteins/metabolism* ; DNA Methylation ; Mixed Function Oxygenases/metabolism* ; 5-Methylcytosine/analogs & derivatives* ; Animals ; Embryonic Development/genetics* ; Neoplasms/genetics* ; Dioxygenases/metabolism*

Objective To investigate the clinical features of pulmonary lymphoma and to get a better understanding of this disease. Methods Clinical data of 253 lymphoma patients in the Department of Lymphoma and Hematology in Jilin Cancer Hospital from October 2014 to March 2017 were retrospectively analyzed. The patients were divided into 30 cases of pulmonary lymphoma (lung lymphoma group) and 223 cases of non-pulmonary lymphoma (the control group). Rate assay and latex turbidimetry was used to detect lactic dehydrogenase (LDH) and β2macroglobulin (β2-MG) respectively. The expressions of programmed death 1 (PD-1), programmed death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) in peripheral blood CD4 +CD8 +T lymphocytes were detected by using flow cytometry. The count and measurement data of both groups were compared by using χ 2test and t test respectively. Results The patients in pulmonary lymphoma group showed secondary lesions. The proportion of smoking people in pulmonary lymphoma group was higher than that in the control group [43.3 % (13/30) vs. 24.2 % (54/223), χ 2＝ 4.964, P＝ 0.026]. The proportion of the patients in Ⅲ-Ⅳ stage in pulmonary lymphoma group was higher than that in the control group [93.3 % (28/30) vs. 57.0 % (127/223), χ2＝ 14.750, P < 0.001]. The proportion of the patients with higher international prognostic index (IPI) score in pulmonary lymphoma group was higher than that in the control group (χ2＝ 21.888, P < 0.001). The proportion of the patients with increased expression of β2-MG in pulmonary lymphoma group was higher compared with the control group [66.7 % (20/30) vs. 50.2 % (112/223), χ2＝6.682, P ＝0.091]. The proportion of the patients with the increased LDH was higher compared with the control group [63.3 % (19/30) vs. 41.5 % (86/223)], and the difference was statistically significant (χ2＝ 6.682, P ＝ 0.010). Diffuse large B-cell lymphoma (DLBCL) was the common pathological type in pulmonary lymphoma group (15 cases), followed by Hodgkin lymphoma (7 cases); imaging showed single mass or nodular type, multiple masses or nodular type, bilateral pulmonary infiltration, pleural effusion were 36.7 % (11/30), 30.0 % (9/30), 63.3 % (19/30) and 36.7 % (11/30), respectively. There were no statistical differences in the protein expression of immune check points such as PD-1, PD-L1 and CTLA-4 in both groups (all P ＞ 0.05). Conclusions Pulmonary DLBCL should be considered a secondary disease, but not a primary lesion. Smoking history is a risk factor for lymphoma patients with pulmonary involvement. Pulmonary lymphoma is similar to other extra-nodal lymphoma with high IPI scores, advanced stage and elevated LDH.

This study was aimed to establish an HPLC method for simultaneous determination of the content of echinacoside, acteoside and isoacteoside in Total Cistanchis glycosides Capsules. Waters C18 column (4.6 mm ×150 mm, 5 μm) was used with the mobile phase of methanol-0.1% formic acid at a flow rate of 1.0 mL·min-1. The detection wavelength was set at 330 nm. The column temperature was maintained at 30℃ . The results showed that the linear ranges of echinacoside, acteoside and isoacteoside were in the range of 27.792-277.92 μg·mL-1 (r = 0.9996,n = 6), 2.4184-24.184 μg·mL-1 (r = 0.9996, n = 6), 5.106-51.06 μg·mL-1 (r = 0.9998, n = 6). The average recoveries of three components were in accordance with the determination requirement. It was concluded that the method was simple and accurate, which can be used in the content determination of echinacoside, acteoside and isoacteoside in Total Cistanchis glycosides Capsules.