Heart Diseases/genetics* ; Humans ; Nuclear Proteins ; Transcription Factors

Tumor immune checkpoint therapy is a clinical treatment strategy developed based on the new principle of the inhibition of negative immune regulation. In this article, the tumor immune checkpoint therapy and the drug delivery strategies were reviewed, mainly including immunity and tumor therapy, tumor immune checkpoint therapy and its mechanism of action, clinical application of tumor immune checkpoint therapy and therapeutic drugs, immune resistance of programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PDL1) treatment and countermeasures, drug delivery strategies for tumor immune checkpoint therapeutic agents, etc. As a revolutionary new immunotherapy strategy, tumor immune checkpoint therapy has shown obvious superior therapeutic efficacy in a variety types of tumor. However, tumor immune checkpoint therapy is also faced with a big challenge, namely, immunotherapy resistance. With the discovery of new mechanism, the continuous development of new therapeutic drugs and delivery strategies, tumor immune checkpoint therapy is expected to further improve the clinical efficacy of tumor.

The in situ gel systems can form gel in situ after administration to achieve sustained release, thus provides a promising strategy for drug delivery systems. The aim of this study was to design and prepare in situ gel systems for the oral delivery of ibuprofen (IBU-ISG) and study its pharmacokinetics in Beagle dogs. The characteristics of the basic material of gellan gum (Kelcogel, Kel) and sodium alginate (Manugel, M) were studied through investigating the complex viscosity of the Kel or M solution with or without different concentrations of calcium ion or sodium citrate to ascertain the amount range of the excipients. The measurement of complex viscosity of the solution (0. 5% Kel and 1% M) with different concentrations of sodium citrate and calcium ion was carried out to select the suitable proportion of calcium ion and sodium citrate. The formulation of binary IBU-ISG was optimized by monitoring the complex viscosity before gelling in vitro release property. The optimized formulation contains 1.0% sodium alginate, 0.5% gellan gum, 0. 21% sodium citrate and 0.056% calcium chloride. A single oral dose of IBU-ISG and reference formulation (IBU suspension) were given to each of the 6 healthy Beagle dogs, ibuprofen in plasma at different sampling times was determined by RP-HPLC. The pharmacokinetics parameters in 6 Beagle dogs were calculated. The Tmax of IBU-ISG and reference formulation were (1.8 +/- 0.6) and (0.4 +/- 0. 1) h. The Cmax values were (29.2 +/- 7.6) and (37.8 +/- 2.2) microg x mL(-1). The T(1/2) were (2.3 +/- 0.5) and (2.0 +/- 0.9) h, and the AUC(0-t) were (131.0 +/- 38.6) and (117.3 +/- 23.1) microg x mL(-1) x h, respectively. The binary IBU-ISG was successfully prepared.
Administration, Oral ; Alginates ; chemistry ; Analgesics, Non-Narcotic ; administration & dosage ; blood ; pharmacokinetics ; Animals ; Area Under Curve ; Calcium Chloride ; chemistry ; Citrates ; chemistry ; Delayed-Action Preparations ; Dogs ; Drug Compounding ; methods ; Drug Delivery Systems ; Excipients ; Female ; Glucuronic Acid ; chemistry ; Hexuronic Acids ; chemistry ; Ibuprofen ; administration & dosage ; blood ; pharmacokinetics ; Male ; Polysaccharides, Bacterial ; chemistry ; Viscosity

The essence of endogenous turbidity in Chinese medicine (CM) is different from cream, fat, phlegm, retention, damp, toxicity, and stasis. Along with the development of modern scientific technologies and biology, researches on the essence of endogenous turbidity should keep pace with the time. Its material bases should be defined and new connotation endowed at the microscopic level. The essence of turbidity lies in abnormal functions of zang-fu organs. Sugar, fat, protein, and other nutrient substances cannot be properly decomposed, but into semi-finished products or intermediate metabolites. They are inactive and cannot participate in normal material syntheses and decomposition. They cannot be transformed to energy metabolism, but also cannot be synthesized as executive functioning of active proteins. If they cannot be degraded by autophagy-lysosome or ubiquitin-prosome into glucose, fatty acids, amino acids, and other basic nutrients to be used again, they will accumulate inside the human body and become endogenous turbidity. Therefore, endogenous turbidity is different from final metabolites such as urea, carbon dioxide, etc., which can transform vital qi. How to improve the function of zang-fu organs, enhance its degradation by autophagy-lysosome or ubiquitin-prosome is of great significance in normal operating of zang-fu organs and preventing the emergence and progress of related diseases.
Autophagy ; Humans ; Medicine, Chinese Traditional ; Proteasome Endopeptidase Complex

OBJECTIVETo induce the differentiation of K562/MDR1 cells into dendritic cells (DC) with multidrug resistance property.

METHODSK562/MDR1 cells and K562 cells were cultured in the presence of GM-CSF and IL-4 to generate DC and matured by TNF-α. On d14 K562/MDR1-DC and K562-DC cells were harvested and the expressions of CD1a, CD83, CD80, CD86, HLA-ABC and HLA-DR were assessed by flow cytometry (FCM). The antigen presentation function of K562/MDR1-DC and K562-DC was determined by allogenic mixed lymphocyte reaction (Allo-MLR). The expression of P-glycoprotein and the intracellular accumulation of daunorubicin (DNR) were detected by FCM. The sensitivity of K562/MDR1-DC and K562-DC cell to vincristine, adriamycin was measured using MTT assay.

RESULTSBoth K562/MDR1 and K562 cells were differentiated into dendritic cells in the presence of cytokine cocktails, showing the morphologic and immunophenotypic characteristics of DC. K562/MDR1-DC more markedly enhanced proliferation of allogeneic lymphocytes in MLR than K562-DC. High level expression of P-glycoprotein and efflux of DNR were demonstrated in K562/MDR1-DC. K562/MDR1-DC showed multidrug resistance property, with higher IC(50) to VCR and ADM than that of K562-DCs.

CONCLUSIONK562/MDR1 cells can be differentiated into DC with the presence of cytokines, the induced K562/MDR1-DC cells express high level of P-glycoprotein and acquire the multidrug resistance property.

ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; Cell Differentiation ; drug effects ; Dendritic Cells ; cytology ; Drug Resistance, Multiple ; Granulocyte-Macrophage Colony-Stimulating Factor ; pharmacology ; Humans ; Interleukin-4 ; pharmacology ; K562 Cells ; cytology ; Transfection ; Tumor Necrosis Factor-alpha ; pharmacology

Objective To observe the influence of long-term treatment with inhaled corticosteroid on biochemical bone indexes and bone mineral density (BMD) in children with asthma. Methods The design was a randomized, paralleled group study with 3 low dose regiments of 100, 200,300 micrograms of budesonide per day in 45 children with asthma aged 5-8 years old for 12 months. Before inhaled corticosteroid therapy and 6th,12th month,clinical effects were observed and lung function(FEV1) was measured; concentration of serum osteocalcin(OST),insulin-like growth factor-1(IGF-1),bony alkaline phosphatase (BALP) and urinary deoxypyridinolin: creatinine (DPD/Cr) were measured; BMD was examined by dual energy X-ray absorptiometry. Results Clinical evaluation was improved and there was significant increase in FEV1 of asthmatic children. The amount of serum OST was slightly higher,yet no significant compared with that of normal control group. There was significant increase of serum BALP in asthmatic children after treatment; there was significant increase in serum IGF-1 of patients group after treatment compared with in normal children at the same age group; there was significant decrease in urinary DPD/Cr after treatment.There was no significant decrease in BMD before and after treatment at the hip (neck of femur , trochanter of femur ,Ward′s triangle),the lumber area of the spine (L2-4) and forearm (ultradis, distal). Conclusion Long-term treatment with low does corticosteroid dose not restrictedly affect bone metabolism and BMD in children with asthma.

OBJECTIVE: To examine the hepatitis C virus (HCV) infection in systemic lupus erythematosus (SLE) patients, to investigate the influence of HCV infection, and to analyze the clinical appearances and experimental immunological characters of SLE. METHODS: Serum of 92 SLE patients and 58 normal control people was taken, and the HCV infection and experimental immunological characters were detected. SLE patients were divided into HCV infection group and non-HCV infection group according to the detective results. The immunological characters and clinical appearances were analyzed in the two groups. RESULTS: Thirteen of the 92 SLE patients were HCV positive, while only 2 of the 58 normal controls were positive. There were no significant differences in the clinical features including oral ulcer, arthritis, serositis, nephropathy, neural disorder, fever, as well as in the laboratory results including ANA, Anti-Ro/SSA, Anti-La/SSB, Anti-Sm, IgG and IgM in the two groups. HCV positive patients showed a lower frequency of butterfly erythema and positivity for Anti-dsDNA, and a higher frequency of cutaneous vasculitis, liver damage, positivity for RF and low C3, C4 levels. CONCLUSION Patients with SLE showed a high prevalence of HCV infection, and HCV may cause some clinical and immunological changes in SLE.
Adolescent ; Adult ; Female ; Hepatitis C ; complications ; Humans ; Lupus Erythematosus, Systemic ; complications ; Male ; Middle Aged ; Young Adult

OBJECTIVETo study the dynamic changes of T lymphocyte subsets of AIDS patients during more than 24 months of highly active antiretrovirus therapy (HAART) with successful suppression of HIV replication and different CD4 + T cell restoration.

METHODSTotally 45 AIDS patients who had received HAART for more than 24 months were included. During HAART (including DO, M3, M6, M12, M18, and M24), the number of plasma HIV-1 RNA was measured quantitatively using the bDNA assay, and T lymphocyte subsets including CD3 + CD4 + cells, CD3 + CD8 + cells, naive CD4 + cells (CD4 + CD45RA + CD62L +), CD4 + CD28 + cells , and CD8 + CD38 + cells were detected with flow cytometer.

RESULTSAmong 45 patients, 24 patients (53.3%) whose plasma viral load decreased to less than 500 copies/ml at M6 and maintained to M24 were classified into three groups according to the CD4 + T cell count increments on M24 (compared with DO): group A (< 100/mm3), group B (100-200/mm3), and group C (> 200/mm3). After the initiation of HAART, T lymphocyte response, including CD4 + T cell counts, naive CD4 + cell counts, percentages of CD4 + CD28 + cells in these patients were improved gradually, while CD8 + CD38 + percentage decreased. The improvement of T lymphocyte response in group C was most remarkable even with highest plasma viral load and lowest CD4 T cell count on DO. Compared with group A and B, group C had significantly better improvement not only in the quantities of CD4 + T cell, but also in the CD28 + expression and naive CD4 + T cell populations.

CONCLUSIONST lymphocyte response of AIDS patients can be effectively reconstituted by HAART. Different dynamics of CD4 + CD28 + and naive CD4 + populations may considerably contribute to the quantity and cellular function restoration of CD4 + T lymphocyte.

Acquired Immunodeficiency Syndrome ; drug therapy ; immunology ; Anti-HIV Agents ; therapeutic use ; Antiretroviral Therapy, Highly Active ; CD4-Positive T-Lymphocytes ; immunology ; HIV ; drug effects ; physiology ; Humans ; T-Lymphocyte Subsets ; Virus Replication ; drug effects

Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells for transplantation with success being associated with the total nucleated cell (TNC) count, CD34(+) cells and colony-forming unit-granulocyte-macrophage (CFU-GM) content infused. This study was purposed to clarify the impact of maternal and neonatal factors on hematopoietic potential of UCB product. UCB samples were screened, processed, tested and cryopreserved according to the Standard Operation Procedure (SOP) of Guangzhou cord blood bank (GZCBB). Relationship of hematopoietic cell parameters with maternal and neonatal characteristics for 4615 UCB units was analyzed retrospectively. The results showed that both collected volume (Mean ± SD: 95.23 ± 22.42 ml; Median: 91.85 ml) and initial TNC [Mean ± SD: (1.34 ± 0.49) × 10(9); Median: 1.25 × 10(9)] correlated well with postprocessed TNC [Mean ± SD: (1.21 ± 0.42) × 10(9); Median: 1.14 × 10(9); p < 0.001], CD34(+)count [Mean ± SD: (5.14 ± 4.55) × 10(6); Median: 4.08 × 10(6); p < 0.001] and CFU-GM content [Mean ± SD: (9.72 ± 8.66) × 10(5); Median: 7.53 × 10(5); p < 0.001]. As for donor factors, only infant birth weight correlated strongly with volume collected and all hematopoietic cell parameters (p < 0.001). UCB samples from bigger babies had higher collected volume, TNC, CD34(+) count and CFU-GM content (p < 0.001). Mother's age had no correlation with all the above parameters. Gestational age correlated positively with initial/postprocessed TNC (p < 0.001) and negatively with CD34(+) count (p = 0.04), but no relation with collected volume and CFU-GM content. Cesarean section produced superior volume (Mean ± SD: 97.05 ± 22.23 ml vs 92.53 ± 22.43 ml; Median: 94.08 ml vs 88.82 ml; p < 0.001), but inferior cell count than vaginal delivery (p < 0.001). Male infants had more initial volume and CD34(+) count (Mean ± SD: 96.41 ± 22.31 ml vs 93.95 ± 22.47 ml; Median: 93.27 ml vs 90.14 ml; p < 0.001); [Mean ± SD: (5.28 ± 5.04) × 10(6) vs (5.00 ± 3.94) × 10(6); Median: 4.18 × 10(6) vs 3.94 × 10(6); p < = 0.042], but lower initial and postprocessed TNC than female ones [Mean ± SD: (1.31 ± 0.50) × 10(9) vs (1.37 ± 0.47) × 10(9); Median: 1.22 × 10(9) vs 1.28 × 10(9); p < 0.001]; [Mean ± SD: (1.18 ± 0.42) × 10(9) vs (1.24 ± 0.41) × 10(9); Median: 1.10 × 10(9) vs 1.17 × 10(9); p < 0.001], while no significant difference of CFU-GM were found between male and female infants. It is concluded that these data may be helpful to optimize the UCB donor selection and improve cost efficiency of UCB bank resource. The heavier infants after vaginal delivery should be selected and large-volume units with higher TNC should be chosen at first.
Adult ; Birth Weight ; Blood Banks ; methods ; Cord Blood Stem Cell Transplantation ; methods ; Delivery, Obstetric ; Donor Selection ; Female ; Fetal Blood ; cytology ; immunology ; Gestational Age ; Hematopoietic Stem Cells ; Humans ; Infant, Newborn ; Male ; Maternal Age ; Pregnancy ; Young Adult

OBJECTIVETo study the effects of different parameters (frequency, intensity, needle-retained time and treatment interval) of electroacupuncture at Fenglong (ST 40) for adjusting blood lipids, so as to find out the optimization parameter.

METHODSFifty-four cases meeting the criteria for hyperlipoidemia were randomly divided into 27 groups with orthogonal design L27 (3(13) ). According to the orthogonal design program they were treated with electroacupuncture at Fenglong (ST 40). Ten sessions constituted one course with a one week's interval between two course. The treatment was given for 2 courses.

RESULTS(1) The parameters of EA at Fenglong (ST 40) for regulating blood lipids in primary and secondary orders are: frequency, needle-retained time, interval of treatment, intensity. (2) The parameters of EA at Fenglong (ST 40) for various programs in regulating various blood lipids are: for TG, frequency AM 50 Hz, needle-retained time 20 ain, intensity 1 mA, twice each week; for TC, frequency AM 100 Hz, needle-retained time 30 min, intensity 1 mA, once every other day; for LDL-C, frequency Am 100 Hz, needle-retained time 30 min, intensity tolerable and comfortable, once every other day.

Acupuncture Points ; Aged ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Electroacupuncture ; methods ; Female ; Humans ; Hyperlipidemias ; blood ; therapy ; Lipids ; blood ; Male ; Middle Aged