Child ; Encephalitis, Viral ; pathology ; Enterovirus A, Human ; Enterovirus Infections ; complications ; Heart Failure ; etiology ; Humans ; Respiratory Insufficiency ; etiology

Glycyrrhizae Radix et Rhizoma is one of the commonly used Chinese materia medica in clinic. It has the effects of tonifying spleen and replenishing qi, clearing heat and removing toxin, dispelling phlegm, relieving cough, relieving pain, and reconciling various drugs. Its main active ingredients are saponins, flavonoids and polysaccharides. Among them, glycyrrhizic acid and glycyrrhetinic acid not only have inhibitory effects on liver cancer, lung cancer, breast cancer and other cancers, but also can be combined with chemotherapeutic drugs to increase drug efficacy as well. At the same time, they can be developed as drug carrier for drug delivery to solve the problems of low water solubility, low bioavailability, high toxicity and side effects of drugs. It was found that their solubilization may be closely related to their amphiphilic structure, which is expected to further explore the role of their carrier characteristics in drug transmembrane transport. Based on the anti-tumor mechanisms of Glycyrrhizae Radix et Rhizoma, the applications of glycyrrhizic acid and glycyrrhetinic acid in drug delivery systems were systematically summarized in this paper, which could provide reference for the further study of glycyrrhizic acid and glycyrrhetinic acid as excipients of drug delivery systems.

Objective： This study was designed to explore the significance and the role of wild-type p53 (wt-p53) gene and mutant p53 gene(mt-p53) transfer on human glandular lung cancer cell growth in nude mice. Methods： wt-p53 gene and mt-p53 gene were transfected and lipofectin-mediated into the human glandular lung cancer cell line GLC-82. And the growth of gene-transfected cell lines were observed in vitro and in vivo. Results： The colony number in the colong-forming experiment and the volume and weight in nude mice were greater in the mf-p53 tranfecting cells group than in the control group. The tumor resulting from the cells transfected with the wt-p53 gene grew more slowly and was smaller than that from control GLC-82 cells. In contrast, the tumor from the cells transfected with the mt-p53 gene grew faster than that produced by cells transfeted with the wt-p53 gene and that produced by control GLC-82 cells. Conclusion： The wild-type p53 gene could inhibit the glandular lung cancer cell growth in nude mice and the mutant p53 gene could enhance the glandular lung cancer cell growth in nude mice.

Objective To observe the effects of urokinase in the treatment of thrombosis in hemodialysis patients with arteriovenous fistulae and to discuss simple, safe and effective methods of thrombolysis. Methods Local injections of urokinase were applied in 23 hemodialysis patients for 43 times to treat thrombosis in fistula, then the effects were observed, and the changes between before treatment and after treatment of several index, such as activated partial thromboplastin time( APTT), Fibrinogen( Fbg), international normalized ratio (INR), Prothrombin Time (PT), thrombin time(TT) were compared. Results The thrombolytic therapies were used in 23 cases for 43 times in total, in which 33 times (76.7% ) received success, and there were no severe complications occurred. The effectiveness was related to the duration of thrombosis. There were no significant differences in comparison of APTT, Fbg, INR, PT, TT before and after urokinase administration. Conclusions Urokinase was effective in thrombolytic therapy for hemodialysis patients with thrombosis in arteriovenous fistula.

The anti-inflammatory active ingredients of Zhi-Shi-Zhi-Zi-Chi-Tang (ZSZZCT), a traditional Chinese medicine formula, were predicted and identified using an approach based on activity index, LC-MS, semi-preparative LC and NMR. Firstly, the whole extract of ZSZZCT was analyzed using liquid chromatography-quadrupole time of flight-mass spectrometry (LC-Q-TOF-MS) and liquid chromatography - ion trap mass spectrometry (LC-IT-MS), 79 constituents were detected and 39 constituents were identified unambiguously or tentatively. Subsequently, the whole extract of the formula was separated into multiple components and the activity index method was used to calculate index values of the 79 constituents by integrating the chemical and pharmacological information of multiple components. Four polymethoxyl flavones were predicted as the major active constituents according to the activity index values. Furthermore, three polymethoxyl flavones were prepared using the strategy with semi-preparative LC guided by LC-MS, and their anti-inflammatory activities were validated. The results show that three polymethoxyl flavones with higher positive index values, i.e., 3, 5, 6, 7, 8, 3', 4'-heptamethoxyflavone, 3-hydroxynobiletein and tangeretin had significant anti-inflammatory effects. In conclusion, the predicted results indicated that the activity index method is feasible for the accurate prediction of active constituents in TCM formulae.
Animals ; Anti-Inflammatory Agents ; chemistry ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Flavones ; chemistry ; isolation & purification ; pharmacology ; Lipopolysaccharides ; toxicity ; Macrophages ; drug effects ; metabolism ; Medicine, Chinese Traditional ; Mice ; Molecular Structure ; Nitric Oxide ; metabolism ; Plant Extracts ; chemistry ; pharmacology ; Plants, Medicinal ; chemistry ; RAW 264.7 Cells

Objective:To investigate the effects of Xiongcan Yishen Formula(XYF)on ferroptosis in mouse TM3 Leydig cells after oxidative stress injury(OSI)induced by H2O2.Methods:An oxidative stress injury model was established in mouse TM3 Leydig cells using H2O2 induction.The modeled TM3 cells were randomly divided into OSI group,XYF group,the ferroptosis inhibitor Ferrostatin-1(F-1)group,and F-1+XYF group,which were respectively intervened with blank serum,20%drug-containing serum,2μmol/L F-1,and2μmol/L F-1+20%drug-containing serum.A control group(normal TM3 cells+blank serum)was also set up.The morphology of cells in each group was observed,and the levels of testosterone,superoxide dismutase(SOD),reactive oxygen spe-cies(ROS),malondialdehyde(MDA),ferritin heavy chain 1(FTH1),solute carrier family 7 member 11(SLC7A11),glutathione(GSH),glutathione peroxidase 4(GPX4),fatty acid CoA ligase 4(FACL4),total iron ions,and ferrous ions were detected.Re-sults:Compared with the model group,the control group showed significantly decreased expression of ROS,MDA,FACL4,total iron,and ferrous ions(P<0.05),and significantly increased levels of testosterone,SOD,GSH,FTH1,SLC7A11,and GPX4(P<0.05).The male silkworm kidney-tonifying formula group significantly promoted testosterone secretion by TM3 cells and upregulated the expression of FTH1,SLC7A11,GPX4,GSH,and SOD in TM3 cells(P<0.05),while significantly downregulating ROS,MDA,FACL4,total iron ions,and ferrous ions(P<0.05).Conclusion:Following H2O2 exposure,oxidative stress can induce ferroptosis in mouse TM3 Leydig cells.XYF can antagonize OSI and ferroptosis in TM3 cells by activating the SLC7A11/GSH/GPX4 axis,which may underlie the mechanism of XYF in the treatment of male late-onset hypogonadism.

Traditional Chinese medicines (TCMs), with a history of thousands of years, are widely used clinically with effective treatment. However, the drug delivery systems (DDSs) for TCMs remains major challenges due to the characteristics of multi-components including alkaloids, flavones, anthraquinones, glycosides, proteins, volatile oils and other types. Therefore, the novel preparations and technology of modern pharmaceutics is introduced to improve TCM therapeutic effects due to instability and low bioavailability of active ingredients. Salviae Miltiorrhizae Radix et Rhizoma, the radix and rhizomes of Salvia miltiorrhiza Bunge (Danshen in Chinese), is a well known Chinese herbal medicine for protecting the cardiovascular system, with active ingredients mainly including lipophilic tanshinones and hydrophilic salvianolic acids. In this review, this drug is taken as an example to present challenges and strategies in progress of DDSs for TCMs. This review would also summary the characteristics of active ingredients in it including physicochemical properties and pharmacological effects. The purpose of this review is to provide inspirations and ideas for the DDSs designed from TCMs by summarizing the advances on DDSs for both single- and multi-component from Danshen.

BACKGROUND: The mortality rate among patients with nasopharyngeal carcinoma (NPC) has improved significantly with the advent of chemoradiotherapy strategies. However, distant metastasis remains problematic. Tumor-specific reactivity in cancer patients has been detected exclusively in CD39+ T cells, particularly in CD39+CD103+ T cells. Circulating cancer-specific T cells are important for protecting against metastasis. This study aimed to evaluate the predictive value of circulating CD39+CD8+ T cells for metastasis in patients with NPC. METHODS: We performed a cross-sectional, longitudinal study of 55 patients with newly diagnosed NPC of stage III-IVa. All patients were initially treated with standard combined chemoradiotherapy. Blood samples were obtained from 24 patients before and at 1 month and 6 months after treatment. T cell expression of CD39 and CD103, together with the markers of T cell exhaustion programmed death-1 (PD-1)/T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) and markers of cell differentiation CD27/CC-chemokine receptor 7/CD45RA, was examined by flow cytometry. The Wilcoxon rank-sum test analysis was used to analyze the differences between two groups. Kaplan-Meier analysis was used for analysis of progression-free survival (PFS). RESULTS: The expression of circulating CD39+CD8+ and CD39+CD103+ CD8+ T cells was significantly higher in patients without distant metastasis (CD39+CD8+: 6.52% [1.24%, 12.58%] vs. 2.41% [0.58%, 5.31%], Z=-2.073, P=0.038 and CD39+CD103+CD8+: 0.72% [0.26%, 2.05%] vs. 0.26% [0.12%, 0.64%], Z=-2.313, P = 0.021). Most CD39+ T cells did not express PD-1 or Tim-3. Patients with high expression of CD39+CD103+CD8+ T cells had better PFS than patients with low expression (log rank value = 4.854, P = 0.028). CD39+CD8+ T cells were significantly elevated at 1-month post-treatment (10.02% [0.98%, 17.42%] vs. 5.91% [0.61%, 10.23%], Z = -2.943, P = 0.003). The percentage of advanced differentiated CD8+ T cells also increased at 1-month post-treatment compared with pre-treatment (33.10% [21.60%, 43.05%] vs. 21.00% [11.65%, 43.00%], Z = -2.155, P = 0.031). There was a significant correlation between elevated CD39+CD8+ T cells and increased effector memory T cells (intermediate stage: r = 0.469, P = 0.031; advanced stage: r = 0.508, P = 0.019). CONCLUSIONS CD39+CD8+ circulating T cells have preserved effector function, contributing to an improved prognosis and a reduced risk of metastasis among NPC patients. These cells may thus be a useful predictive marker for a better prognosis in patients with NPC.
CD8-Positive T-Lymphocytes ; Chemoradiotherapy ; Cross-Sectional Studies ; Humans ; Longitudinal Studies ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms/therapy* ; Prognosis

Objective: To investigate the relationship between hemoglobin and serum uric acid in adults with various glucose metabolism status. Methods: The demographic data and biochemical indicators of the adult population who had received physical examination in the Second Medical Center of the PLA General Hospital from January 2018 to December 2021 were collected. The subjects were divided into two groups according to the level of serum uric acid: the normal uric acid group and the hyperuricemia group. The relationship between hemoglobin (stratified into four levels of Q₁ to Q₄ by the quartile) and serum uric acid was quantified by using Pearson correlation and logistic regression analysis. The effects of age and glucose metabolism status on the relationship between hemoglobin and serum uric acid were analyzed. Results: A total of 33 183 adults were enrolled with age (50.6±10.0) years. The level of hemoglobin in the normal uric acid group (142.61±14.24) g/L was significantly lower than that in the hyperuricemia group [(151.79±11.24) g/L, P<0.001]. Univariate Pearson correlation analysis showed that hemoglobin was positively associated with serum uric acid (r=0.444, P<0.001). After adjusting for related confounding factors, multivariate logistic regression analysis showed that hemoglobin was associated with serum uric acid, and the OR values (95%CI) of hemoglobin Q₂ to Q₄ group were 1.29 (1.13-1.48), 1.42 (1.24-1.62) and 1.51 (1.32-1.72), respectively (P_trend<0.001) when compared with hemoglobin Q₁ group. Subgroup analysis and hierarchical interaction analysis suggested that with the increase of hemoglobin, the serum uric acid in the age<60 years subgroup, normal glucose subgroup and prediabetes subgroup increased gradually (P_trend<0.05 and P_interaction<0.001). Conclusion: The association between hemoglobin and serum uric acid in adults is affected by age and glucose metabolism status.
Humans ; Adult ; Middle Aged ; Uric Acid ; Hyperuricemia/epidemiology* ; Hemoglobins ; Prediabetic State ; Glucose ; Risk Factors

Cryptotanshinone (CPT), an active ingredient with the inhibitory effect on brain glioma cells, is trapped with poor solubility and low tumor permeability. Therefore, it is urgent to design nano drug delivery systems characterized with deep penetration and accurate targeting. In the present study, tLyp-1 modified liposomes loaded with CPT (tLipo/CPT) was prepared by emulsion solvent evaporation method. Peptide tLyp-1 which targeting tumor angiogenesis and neuropilin receptors (NRP) was modified on surface of CPT liposomes, with the aim of active targeting brain glioma cells and further release CPT precisely. The size and polymer dispersity index (PDI) of tLipo/CPT were (162.2 ± 14.6) nm and 0.24 ± 0.03. The optimal molar ratio of tLyp-1 modified on CPT liposomes was 0.5% determined by intracellular fluorescence parameters. The morphology displayed a smooth sphericity structure as determined by transmission electron microscope. Efficiency of CPT encapsulated in tLipo/CPT was detected by high performance liquid chromatography. The encapsulation efficiency of CPT was (70.06 ± 7.22) %. Liposomes modified with tLyp-1 peptide (tLipo) were internalized more than liposomes not modified with tLyp-1 (Lipo) by GL261 cells. Fluorescence intensity of tLipo in GL261 cells increased 40% than that of Lipo. Furthermore, we proved that the intake of tLipo/CPT in GL261 cells was mediated by NRP-1 receptor. MTT analysis indicated that tLipo/CPT significantly inhibit the proliferation of GL261 cells. The half maximal inhibitory concentration (IC₅₀) was 5.70 μmol·L^-1. In vitro blood-brain barrier (BBB) model experiment indicated that tLipo/CPT could penetration across BBB. Moreover, in vivo fluorescence biodistribution study indicated tail vein injection of DiR labeled tLipo after 0.5 h, DiR fluorescence could be observed in the brain of mice. Even after 24 h, DiR fluorescence still was observed in the brain. Our research certified that tLipo/CPT can penetrate the BBB and show effect of anti-glioma by inhibiting the proliferation of GL261 cells. The animal experiment was carried out in accordance with protocol evaluated and approved by the Ethics Committee of Nanjing University of Chinese Medicine.