There are two kinds of treatments on Alzheimer's disease (AD) rat by transplanting neural stem cells (NSCs),i.e.the replacing cell curing and the gene therapy.By replacing method,the AD rats showed signs of recovering to some extent on both histomorphology and behavior after transplanting NSCs into their brains.Transplanting NSCs along with the nerve nutrition factor (NTFs) showed better curative effects than NSCs transplantation alone.However,little is known about the molecular mechanism involving in the development of NSCs in vivo conditions.And the blindness of the treatment hindered the comparison of various affecting factors.The NSCs gene therapy is still in initial studying,with the effects of both cell replacement and gene therapy.This treatment genetically modified NSCs mainly by unitary nutrition fators such as nerve growth factor (NGF),brain-derived neurotrophic factor (BDNF),and glial cell line-derived neurotrophic factor (GDNF).And it was almost known nothing about the exogenous gene expression efficiency,the induce differentiation,the restore of function and security after genetically-modified NSCs transplanted into the AD rat brain.The detecting technology of NSCs transplanting curative effects of the AD rat is unitary at present.And the combined method is the developing trend,such as combining the immunohistochemical method with in vivo-tracking,and combining morphology index with the function index.

OBJECTIVEDevelop an LC-MS method to determine evodiamine and rutaecarpine in rats plasma simultaneously. The method was employed to investigate pharmacokinetics of evodiamine and rutaecarpine.

METHODBlood samples were collected in different time after oral administrated with the extracts of Euodiae Fructus, the plasma concentration of evodiamine and rutaecarpine was determined by LC-MS, pharmacokinetic parameters were calculated by WinNonlin 5.1 software.

RESULTThe linear ranges of evodiamine and rutaecarpine were 0.5-100 microg x L(-1) (r = 0.995 9), 1-200 microg x L(-1) (r = 0.999 3) respectively. The average recovery were exceeded 76% (n = 5), the precision of inner-day and inter-day were less than 15%. The pharmacokinetics parameters AUC, t1/2, CL _F of evodiamine were: (2 215.24 +/- 414.49), (4 230.62 +/- 753.77), (13 219.21 +/- 3 740.95) min x ng(-1) x mL(-1); (146.57 +/- 38.38), (114.38 +/- 14.65), (163.37 +/- 8.83) min; (184 607.29 +/- 32 502.21), (192 878.22 +/- 31 897.37), (19 3224.63 +/- 62 278.74) mL x min(-1). The pharmacokinetics parameters AUC, t1/2, CL_F of rutaecarpine were (2 283.53 +/- 298.51), (4 424.84 +/- 276.95), (14 239.93 +/- 3648.27) min x ng(-1) x mL(-1); (167.10 +/- 15.82), (131.58 +/- 20.07), (144.41 +/- 13.65) min; (1 177 340.54 +/- 2 4942.21), (181 262.92 +/- 11 162.22), (177 508.10 +/- 52 611.80) mL x min(-1).

CONCLUSIONThe method described in this report has high sensitivity and selectivity, and was suitable for pharmacokinetic studies of evodiamine and rutaecarpine. The kinetic process of evodiamine and rutaecarpine in rats in vivo were all yielded to be one-compartment model.

Administration, Oral ; Animals ; Evodia ; Indole Alkaloids ; pharmacokinetics ; Male ; Plant Extracts ; pharmacokinetics ; Quinazolines ; pharmacokinetics ; Rats ; Rats, Wistar

OBJECTIVETo develop a LC-MS method to determine paeoniflorin concentration in rats plasma. The method was applied to investigate pharmacokinetics of paeoniflorin in rats in vivo.

METHODBlood samples were collected at different time after oral administration of Radix Paeoniae Alba extract at doses of 0.2, 0.4, 0.8 g x kg(-1). The paeoniflorin concentration in plasma was determined by LC-MS method. Pharmacokinetic parameters were fitted by WinNonlin 5.1 software package.

RESULTThe linear range and the average recovery of paeoniflorin were 2.5-500 microg x L(-1) (r = 999 4) and more than 80% (n = 5) , respectively. The inner- and inter-days precision were both less than 15%. The T1/2 was similar. The relationship between dose and AUC showed good linearity.

CONCLUSIONThe method described in this report has high sensitivity and selectivity, and was suitable for pharmacokinetic study of paeoniflorin. The kinetic process of paeoniflorin in palsma showed two-compartment model after oral administration of Radix Paeoniae Alba extract at doses of 0.2, 0.4, 0.8 g x kg(-1) to rats.

Animals ; Benzoates ; administration & dosage ; blood ; pharmacokinetics ; Bridged-Ring Compounds ; administration & dosage ; blood ; pharmacokinetics ; Chromatography, Liquid ; methods ; Glucosides ; administration & dosage ; blood ; pharmacokinetics ; Male ; Mass Spectrometry ; methods ; Monoterpenes ; Paeonia ; chemistry ; Plant Extracts ; administration & dosage ; blood ; pharmacokinetics ; Rats ; Rats, Wistar

Background::Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-na?ve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-na?ve MM.Methods::This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-na?ve MM patients.Results::A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-na?ve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG +Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1) + DCs, IFN-responding DCs, MHCII + DCs, and immunosuppressive monocytes/macrophages were enriched in patients with treatment-na?ve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that "don’t eat me" -related genes and IFN-induced genes increase in treatment-na?ve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16 + monocytes/macrophages and expression level of CD16. Cell-cell communication analysis indicated that monocytes/macrophages, whose related important signaling pathways include migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-na?ve MM patients. Conclusions::Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.

Objective:To compare the safety and efficacy of 7.5 Fr and 9.5 Fr flexible ureteroscopy in the primary treatment of upper urinary tract calculi with maximum diameter<1.5 cm.Methods:Using a prospective randomized controlled study method, 96 patients with upper urinary tract calculi with maximum diameter<1.5 cm admitted to the Department of Urology, Beijing Friendship Hospital, Capital Medical University from August 2020 to May 2022 were selected as the study subjects. The patients were divided into two groups by random number table method: the experimental group and the control group, with 48 patients in each group. The experimental group patients underwent 7.5 Fr flexible ureteroscopic lithotripsy, while the control group patients underwent 9.5 Fr flexible ureteroscopic lithotripsy. Collect preoperative, intraoperative, and postoperative data from these patients, including success rate of ureteral access sheath insertion, surgical time, lithotripsy time, stone-free rate, ureteral injury status, and complications status. The measurement data were expressed as mean±standard deviation ( ± s), Student- t test was used for comparison between groups; the Chi-square test was used for inter-group comparison of count data, and the Mann-Whitney U test was used for inter-group comparison of rank data. Results:The success rate of primary sheath insertion in the experimental group was 93.8% (45/48), and that in the control group was 79.2% (38/48), the difference between the two groups was statistically significant ( P<0.05). There were no statistically significant difference between the experimental group and the control group in terms of surgical time [(52.0±11.0) min vs (55.1±11.4) min, P>0.05] and lithotripsy time [(26.0±9.3) min vs (23.7±8.7) min, P>0.05]. At four weeks after surgery, the stone-free rate in the experimental group was 93.3% (42/45), while that in the control group was 97.4% (37/38), there was no statistically significant difference between the two groups ( P>0.05). In terms of the degree of ureteral injury, there were 17 patients had grade 0 injury, 27 patients had grade 1 injury, 4 patients had grade 2 injury, and no patient had grade 3 injury in the experimental group; there were 9 patients had grade 0 injury, 23 patients had grade 1 injury, 13 patients had grade 2 injury, and 3 patients had grade 3 injury in the control group; the difference between the two groups was statistically significant ( P<0.05). In terms of complications, there were 22 cases of hematuria, 9 cases of pain, 8 cases of bladder spasm, and 2 cases of mild fever in the experimental group; there were 24 cases of hematuria, 12 cases of pain, 9 cases of bladder spasm, and 1 case of mild fever in the control group; there was no statistically significant difference between the two groups ( P>0.05). Conclusion:The application of 7.5 Fr flexible ureteroscopy and 9.5 Fr flexible ureteroscopy in the primary treatment of upper urinary tract calculi with maximum diameter<1.5 cm can achieve good stone-free rates, but the 7.5 Fr flexible ureteroscopy has a higher success rate of sheath insertion and less damage to the ureter.

Objective To explore the effect of 14-3-3 β gene on biological behavior ofglioma cell line and its mechanism.Methods Conventional cultured SVGp12,U251,U87 and SHG-44 cell lines and U251 cells silenced by 14-3-3[β-small interfering RNA (siRNA) were collected; real time-PCR and Western blotting were used to detect the 14-3-3β gene and protein expressions in these cells.Conventional cultured U251 cells at logarithmic phase were divided into three groups:experimental group (14-3-3β-siRNA transfection),negative control group (siRNA transfection) and blank control group; 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay was used to assess the proliferation of U251 cells,flow cytometry was used to test the cell apoptosis,and cell migration was analyzed by Transwell chamber assay.Results As compared with those in the normal glial cells,14-3-3β gene and protein expression levels in the glioma cells were significantly higher (P＜0.05); as compared with negative control and blank control groups,U251 cells in the experimental group had significantly decreased gene and protein expressions of 14-3-3β,decreased proliferation and migration abilities,significantly increased apoptosis rate and p53 mRNA level (P＜0.05).Conclusion Silence of 14-3-3 β gene decreases U251 cells proliferation and migration through p53 mediated pathway; consequently,a new explanation about how 14-3-3 β regulates glioma cells proliferation and migration can be clarified,and a potential target for glioma treatment can be provided.

Objective To observe the clinical efficacy and safety of external application of Piyan Formula in treating epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKIs)-related rashes.Methods Sixty cases of EGFR-TKIs-related rash patients were randomly allocated into either a treatment group or a control group.The treatment group received external application of Piyan Formula to the rash area twice daily for 14 days.The control group received external application of fucidic acid cream to the rash area twice daily for 14 days.Changes in rash grading,itching grading,quality of life scores and adverse event were observed and recorded in both groups.At the same time,levels of hypersensitive C-reactive protein,interleukin(IL)-6,and IL-1β were measured before treatment and 24 hours after treatment.Results After treatment,the rash severity,itching severity,and quality of life scores were notably lower in the treatment group compared to the control group(P<0.05).The levels of hypersensitive C-reactive protein,IL-6,and IL-1β exhibited a significant decrease compared to their pre-treatment values.(P<0.05).Compared with the control group,the levels of hypersensitive C-reactive protein,IL-6,and IL-1β decreased in the treatment group,with statistically significant differences(P<0.05).No adverse events related to Piyan Formula or fucidic acid cream occurred during the treatment process.Conclusion External application of Piyan Formula in treating EGFR-TKIs-related rashes shows significant clinical efficacy,can effectively reduce the levels of inflammatory factors,and has high safety,thus warranting clinical promotion.