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1.
Article in Chinese | WPRIM | ID: wpr-928708

ABSTRACT

OBJECTIVE@#To analyze the clinical characteristics of bloodstream infection (BSI) in patients treated by hematopoietic stem cell transplantation (HSCT).@*METHODS@#The clinical characteristics, distribution of pathogenic bacteria causing BSI and drug sensitivity of 910 patients treated by HSCT in our department from January 2013 to June 2020 were retrospectively analyzed.@*RESULTS@#Among 910 HSCT patients, 111 patients were diagnosed as BSI within 100 days after transplantation, and 98 patients showed BSI during the period of agranulocytosis. Multivariate analysis showed that the usage of anti-thymocyte globulin (ATG), long duration of agranulocytosis and low infusion volume of mononuclear cell (MNC) were the independent risk factors affecting BSI after HSCT. Among 121 pathogenic bacteria isolated, 76 Gram-negative (G-) bacteria (62.8%), 40 Gram-positive (G+) bacteria (33.0%), and 5 fungi (4.1%) were detected out. The top three pathogens were Escherichia coli, Staphylococcus epidermidis and Pseudomonas aeruginosa. The drug-resistance rates of Escherichia coli and Klebsiella pneumoniae to carbapenems was 14.3% and 7.7%, respectively, and Pseudomonas aeruginosa was 66.7%. The susceptibility of G+ bacteria to vancomycin, linezolid and teicoplanin was 97.5%, 100% and 100%, respectively. The crude mortality rate of the patients with BSI at 100 days after HSCT was significantly higher than that of patients without BSI (P<0.001).@*CONCLUSION@#The usage of ATG, long duration of agranulocytosis and low infusion volume of MNC are independent risk factors for BSI after HSCT. The pathogens after HSCT are mainly G- bacteria. Pseudomonas aeruginosa is highly resistant to carbapenems. Key words  ;


Subject(s)
Bacteremia/epidemiology , Bacteria , Hematopoietic Stem Cell Transplantation , Humans , Retrospective Studies , Sepsis
2.
Article in Chinese | WPRIM | ID: wpr-928137

ABSTRACT

Toxicity-attenuating compatibility is an effective measure to ensure the safety of Chinese medicine. Involving the origin, processing method, compatibility mode, and dosage, it faces multiple challenges, such as the uncertainty of toxic substances, toxicity latency, indefinite safe dose, complex toxicity-efficacy relationship, and individual difference. As a result, research on clinical safety of Chinese medicine is limited by the consistency at "molecular-cellular-organ-overall" levels, unclear interaction of multiple medicinals and multiple substances, the "toxicity-efficacy-compatibility-syndrome" correlation, and the "dosage-time-toxicity-efficacy" conversion law. Therefore, following the principle of "starting from the clinical practice, verifying via the theoretical basis, and finally applying in clinical practice", we verified the toxicity at "molecular-cellular-organ-overall" levels, revealed the interaction of multiple medicinals and substances, collected evidence at multiple levels, clarified the "dosage-time-toxicity-efficacy" relationship, and tested the consistency between basic and clinical biomarkers. On this basis, we studied the toxicity-alleviating and efficacy-enhancing(preserving) compatibility characteristics, the fate of one medicinal and multiple medicinals in vivo, the molecular mechanism of toxicity, the "dosage-time-toxicity-efficacy" conversion law, and the clinical characteristics of toxic traditional Chinese medicine based on disease and syndrome. The three mechanisms of toxicity-attenuating compatibility reflect the seven-reaction theory in Chinese medicine compatibility. Finally, the strategies for safe use of Chinese medicine were proposed.


Subject(s)
Drugs, Chinese Herbal/toxicity , Medicine, Chinese Traditional , Research Design
3.
Article in Chinese | WPRIM | ID: wpr-910610

ABSTRACT

In China, hepatocellular carcinoma (HCC) accounts for about 50% of cases in the world, which is still challenging. The implementation of multi-disciplinary treatment (MDT) and whole course management of HCC are conducive to improve the prognosis of patients, so as to achieve the goal of increasing by 15% of overall survival of HCC patients as proposed by the "Healthy China 2030" . The standardized management of HCC includes several key points, such as exact diagnosis of the HCC, selection of proper treatment methods, individual postoperative adjuvant therapy and regular follow-up. MDT is the key measure to implement the standardized and whole course management of HCC. Herein, the author tends to summary the experience on standardized management of HCC.

4.
Chinese Medical Journal ; (24): 301-308, 2021.
Article in English | WPRIM | ID: wpr-921264

ABSTRACT

BACKGROUND@#Hepatectomy for hepatocellular carcinoma (HCC) beyond the Milan criteria is shown to be beneficial. However, a high rate of post-operative HCC recurrence hinders the long-term survival of the patients. This study aimed to investigate and compare the impacts of tenofovir (TDF) and entecavir (ETV) on the recurrence of hepatitis B viral (HBV)-related HCC beyond the Milan criteria.@*METHODS@#Data pertaining to 1532 patients who underwent hepatectomy and received antiviral therapy between January 2014 and January 2019 were collected from five centers. Recurrence-free survival (RFS) analysis was performed using the Kaplan-Meier method. Cox proportional hazards regression analysis was performed to determine prognostic factors for HCC recurrence.@*RESULTS@#The analysis incorporates 595 HBV-related HCC patients. The overall 5-year RFS was 21.3%. Among them, 533 and 62 patients received ETV and TDF treatment, respectively. The 1-, 3-, and 5-year RFS rates were 46.3%, 27.4%, and 19.6%, respectively, in the ETV group compared with 65.1%, 41.8%, and 37.2%, respectively, in the TDF group (P < 0.001). Multivariate analysis showed that TDF treatment (hazard ratio [HR]: 0.604, P = 0.005), cirrhosis (HR: 1.557, P = 0.004), tumor size (HR: 1.037, P = 0.008), microvascular invasion (MVI) (HR: 1.403, P = 0.002), portal vein tumor thrombus (PVTT) (HR: 1.358, P = 0.012), capsular invasion (HR: 1.228, P = 0.040), and creatinine levels (CREA) (HR: 0.993, P = 0.031) were statistically significant prognostic factors associated with RFS.@*CONCLUSIONS@#Patients with HCC beyond the Milan criteria exhibited a high rate of HCC recurrence after hepatectomy. Compared to the ETV therapy, TDF administration significantly lowered the risk of HCC recurrence.


Subject(s)
Antiviral Agents/therapeutic use , Carcinoma, Hepatocellular/surgery , Guanine/analogs & derivatives , Hepatectomy , Hepatitis B virus , Hepatitis B, Chronic/drug therapy , Humans , Liver Neoplasms/surgery , Retrospective Studies , Tenofovir/therapeutic use
5.
Article in Chinese | WPRIM | ID: wpr-912016

ABSTRACT

Objective:To investigate the effect of combining aerobic exercise with hyperbaric oxygen therapy on the cognition and oxidative stress of patients with post-stroke cognitive impairment (PSCI).Methods:Forty-five PSCI patients were divided randomly into a hyperbaric oxygen therapy (HBO) group (of 21) and a combination group (of 24). Both groups received HBO therapy, but the combination group also performed 30min of aerobic exercise using a cycle ergometer 5 times a week for 8 weeks. The HBO therapy involved 20min for pressurization, 20min of decompression, 60min of pressurized oxygen inhalation and 10min of air inhalation. The treatment pressure was 0.2MPa (2.0ATA). Before and after the intervention, cognitive functioning was measured using the mini-mental state examination (MMSE) and the Montreal cognitive assement (MoCA). The Barthel index quantified ability in the activities of daily living. Serum glutathione (GSH) and malondialdehyde (MDA) were measured spectrophotometrically.Results:The average MMSE scores of both groups had improved significantly after the treatment, with significantly better improvement in the combination group. After the treatment, the average MoCA score of the combination group had improved significantly while that of the HBO group had not. The average Barthel index scores of both groups improved significantly and there was no significant difference between them after the treatment. The average serum GSH increased after the treatment in the combination group, and the increase was weakly positively correlated with the increase in MMSE scores. The average MDA content of the HBO group decreased after the treatment, and the decrease was positively correlated to the increase in the MMSE scores, but again weakly.Conclusions:Aerobic exercise combined with hyperbaric oxygen therapy can effectively improve cognition among PSCI patients. Increases in serum GSH and decreases in serum MDA are weakly positively correlated with cognitive functioning.

6.
Article in Chinese | WPRIM | ID: wpr-911579

ABSTRACT

Objective:To investigate the clinical impact factors of liver regeneration after hemihepatectomy in patients with hepatocellular carcinoma (HCC).Methods:Patients who underwent hemihepatectomy due to HCC from Sep 2013 to Sep 2018 were included in the study. Liver volumes were calculated by perioperative simulations to analyze the influencing factors of postoperative liver regeneration, and to compare the albumin bilirubin (ABLI) score and the end-stage liver disease (MELD) score at weeks 1, 5, 9, and 13 after operation.Results:A total of 163 patients were included, of which 13 developed postoperative liver failure. The median liver regeneration rates at 1, 5, 9 and 13 weeks after operation were 22.0%, 32.2%, 33.7% and 35.4%, respectively. Multivariate analysis showed that remnant liver volume (RLV) <611.1 cm 3, %RLV and liver cirrhosis were the influencing factors of liver regeneration. ALBI score and MELD score were lower in the low regeneration group compared to the high regeneration group in the first 5 weeks after operation. Conclusion:RLV and cirrhosis are influential factors in postoperative liver regeneration. Liver regeneration proceeded rapidly within 1 week and slowed down until week 5.

7.
Article in Chinese | WPRIM | ID: wpr-911282

ABSTRACT

Objective:To evaluate the changes in proteome in hippocampus and bioinformatics analysis in mice with perioperative neurocognitive disorders (PND).Methods:Clean-grade healthy male C57BL/6 mice, aged 15 months, weighing 30-35 g, were divided into 2 groups ( n=9 each) using a random number table method: control group (group C) and group PND.The model of PND was established by performing open tibial fracture with intramedullary fixation under isoflurane anesthesia in anesthetized mice.The Morris water maze test, open field test and fear conditioning test were performed at 1 day before operation and at 1, 3 and 7 days after operation.At 1, 3 and 7 days after operation, 3 mice with worst cognitive performance in each cognitive function assessments were sacrificed in group P, and three mice were randomly sacrificed in group C. The hippocampal tissues were then obtained, the expression of differentially expressed proteins was identified by high-performance liquid chromatography-mass spectrometry, and Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to analyze the differentially expressed proteins. Results:Compared with group C, the escape latency at different time points was significantly prolonged, and the percentage of time spend on target quadrant and the percentage of freezing time in fear conditioning test were decreased in group P ( P<0.05). There were 21 differentially expressed proteins, of which 12 proteins showed up-regulated expression and 9 proteins showed down-regulated expression.The GO functional analysis showed that the differentially expressed proteins were involved in the process such as the metabolism, signal transmission, regulation of biological processes, formed cell components such as synapses and organelles, and were related to molecular function such as binding and transportation.KEGG signaling pathway analysis showed that there were also differences in MAPK signaling pathway, ErbB signaling pathway, AMPK signaling pathway and the transport of SNARE protein in vesicle and etc. Conclusion:There are 21 differentially expressed proteins in the hippocampus of PND mice, and these proteins are involved in the pathophysiological process probably related to PND such as neuroinflammatory responses, abnormal synaptic structure, mitochondrial dysfunction and decreased autophagy.

8.
Article in Chinese | WPRIM | ID: wpr-908511

ABSTRACT

Intersphincteric resection (ISR) is a limited sphincter preserving surgery for low rectal cancer. The 4K laparoscopic system has the advantage of enhancing the accurate recognition of anatomical structures for operators. The authors investigate the imaging evaluation and technical standard of 4K laparoscopic ISR of low rectal cancer through surgical examples.

9.
Article in English | WPRIM | ID: wpr-888487

ABSTRACT

OBJECTIVES@#To study the survival rate and the incidence of complications of very preterm infants and the factors influencing the survival rate and the incidence of complications.@*METHODS@#The medical data of the very preterm infants with a gestational age of <32 weeks and who were admitted to the Department of Neonatology in 11 hospitals of Jiangsu Province in China from January 2018 to December 2019 were retrospectively reviewed. Their survival rate and the incidence of serious complications were analyzed. A multivariate logistic regression analysis was used to evaluate the risk factors for death and serious complications in very preterm infants.@*RESULTS@#A total of 2 339 very preterm infants were enrolled, among whom 2 010 (85.93%) survived and 1 507 (64.43%) survived without serious complications. The groups with a gestational age of 22-25@*CONCLUSIONS@#The survival rate is closely associated with gestational age in very preterm infants. A low 1-minute Apgar score (≤3) may increase the risk of death in very preterm infants, while high gestational age, high birth weight, and prenatal use of glucocorticoids are associated with the reduced risk of death. A low 5-minute Apgar score (≤3) and maternal chorioamnionitis may increase the risk of serious complications in these infants, while high gestational age and high birth weight may reduce the risk of serious complications.


Subject(s)
Female , Gestational Age , Humans , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases , Infant, Very Low Birth Weight , Pregnancy , Retrospective Studies , Survival Rate
10.
Article in Chinese | WPRIM | ID: wpr-888087

ABSTRACT

Coumarins are the main active components in Psoraleae Fructus. To study the multi-component pharmacokinetics of Psoraleae Fructus, this study established a sensitive and rapid ultra-pressure liquid chromatography coupled to tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of psoralen, isopsoralen, psoralenoside, and isopsoralenoside in rat plasma. After validation, the method was applied to the investigation of pharmacokinetics of psoralen, isopsoralen, psoralenoside, and isopso-ralenoside in rats after single and multiple administration of Psoraleae Fructus extract. The results revealed that the exposure of psoralen and isopsoralen in rat plasma was high after a single intragastric administration of Psoraleae Fructus extract, with an AUC_(0-∞) of 443 619-582 680 and 167 314-276 903 ng·mL~(-1)·h~(-1), respectively. Compared with these two compounds, the exposure of psoralenoside and isopsoralenoside was lower with marked gender difference. After 7-day administration of Psoraleae Fructus extract to rats, the AUC_(0-∞) of psoralen and isopsoralen was 29 701-81 783 and 39 234-89 914 ng·mL~(-1)·h~(-1), respectively, which was significantly lower than that at the first day(P<0.05), and that of psoralenoside and isopsoralenoside was 7 360-19 342 and 8 823-45 501 ng·mL~(-1)·h~(-1), respectively. There was no significant gender difference in exposure of psoralenoside and isopsoralenoside in male and female rats. However, the exposure of psoralenoside and isopsoralenoside in male rats was reduced(P<0.05), and the t_(1/2) and mean residence time(MRT) were shortened, suggesting that the removal of these two compounds from the body was accelerated.


Subject(s)
Administration, Oral , Animals , Benzofurans , Chromatography, High Pressure Liquid , Chromatography, Liquid , Drugs, Chinese Herbal , Ficusin , Furocoumarins/analysis , Glycosides , Psoralea , Rats , Tandem Mass Spectrometry
11.
Acta Pharmaceutica Sinica ; (12): 2426-2446, 2021.
Article in Chinese | WPRIM | ID: wpr-886965

ABSTRACT

Chinese traditional medicine has provided, since ancient times, a basis for health care and medicine to the Chinese nation and for China's national stability. Identification of the constituents responsible for therapeutic and undesired effects of Chinese herbal medicines is a type of key research facilitating the modernization of these medicines. For a complex Chinese herbal medicine, multi-compound pharmacokinetic research is a useful approach to identifying its constituents that are bioavailable (in their unchanged and/or metabolized forms) at loci responsible for the medicine's therapeutic action and to characterizing the compounds' disposition and pharmacokinetics related to the action. In addition, such pharmacokinetic research is also useful for identifying herbal compounds associated with the medicine's adverse effects and drug-drug interaction potential. Over the past decade, great advances have been achieved in the theory, methodology, associated techniques, and their application of such multi-compound pharmacokinetic research, which has become an emerging field in pharmacokinetics. In this perspective, we elaborate on the methodology, technical requirements, and key analytical techniques of multi-compound pharmacokinetic research on Chinese herbal medicines, describe research examples regarding investigation of pharmacokinetics and disposition of a class of bioactive herbal constituents (ginsenosides of Panax notoginseng root) and pharmacokinetics-based identification of potential therapeutic compounds from a dosed Chinese herbal medicine (LianhuaQingwen capsule), and discuss follow-up development for the multi-compound pharmacokinetic research.

12.
Article in Chinese | WPRIM | ID: wpr-884252

ABSTRACT

Surgical robots, as a new means for surgeons, have been gradually applied in orthopedics. Initially, the development of orthopedic robots was stagnant for a long time because of limited techniques available, clumsy equipment, high costs, and low market demands. The recent decade has witnessed rapid growth of artificial intelligence in all walks of life, increasing investment in research and development, reducing manufacture costs and expanding demands for precise and individualized medical treatment so that a wide variety of novel and ingenious robotic systems have been proposed, prototyped, and commercialized in most of the major procedures in orthopedic surgery, including knee and hip replacements, cruciate ligaments surgery, spine surgery, corrective osteotomy, bone tumor surgery, and trauma surgery. This review depicts the history of development and future prospects in application of surgical robots in the field of orthopedics.

13.
Article in Chinese | WPRIM | ID: wpr-878993

ABSTRACT

An UPLC-MS/MS method for rapid and simultaneous determination of psoralen, isopsoralen, apigenin, genistein, bavaisoflavone, neobavaisoflavone, bavachin, bavachinin, psoralenoside, and isopsoralenoside of Psoraleae Fructus in beagle dog plasma was established, and then the method was applied in the pharmacokinetic study after oral administration of Psoraleae Fructus extract to beagle dogs. The pharmacokinetic parameters were calculated by the software of WinNonlin. A Waters HSS-T3 column(2.1 mm×100 mm,1.8 μm)was used for liquid chromatography separation with acetonitrile-water(containing 0.004% formic acid) as the mobile phase for gradient elution.The mass spectrometry was detected using electrospray ion source(ESI) under multi-reaction monitoring mode(MRM), as well as positive ion mode. Analysis time only takes 8.5 min. The methodological study in terms of specificity, accuracy, precision, linear range, recovery, matrix effect, and stability, was validated. The LC-MS analysis method established in this experiment was simple, specific, accurate, reliable, and meet the requirement of pharmacokinetic study in plasma after administration of Psoraleae Fructus extract to beagle dogs. Six beagle dogs received intragastric administration of Psoraleae Fructus extract, T_(max) of 10 chemical components is 1.92-5.67 h; among them, C_(max) of psoralen, isopsoralen, psoralenoside and isopsoralenoside is 383-3 613 ng·mL~(-1), and AUC_(0-∞) is 3 556-18 949 ng·h·mL~(-1), t_(1/2) is 2.45-4.83 h. C_(max) of the remaining six compounds is 0.81-19.9 ng·mL~(-1), AUC_(0-∞ )is 6.54-178 ng·h·mL~(-1), t_(1/2) is 2.95-7.29 h. The UPLC-MS/MS analysis method established in this study was proved to be accurate and sensitive that it can be applied to the pharmacokinetic study of beagle dogs after oral administration of Psoraleae Fructus extract.


Subject(s)
Administration, Oral , Animals , Chromatography, High Pressure Liquid , Chromatography, Liquid , Dogs , Drugs, Chinese Herbal , Plasma , Reproducibility of Results , Tandem Mass Spectrometry
14.
Article in Chinese | WPRIM | ID: wpr-865181

ABSTRACT

Laparoscopic subtotal gastrectomy has become the main treatment of early gastric cancer. The 4K laparoscopic system has the advantage of enhancing the operator′s recognition of various anatomical levels and blood vessels in radical gastrectomy. The authors discussed the reconstruction of digestive tract with Billroth Ⅱ anastomosis in totally laparoscopic distal radical gastrectomy with the aid of 4K laparoscopic technique.

15.
Article in Chinese | WPRIM | ID: wpr-837549

ABSTRACT

@#Objective    To compare the perioperative outcomes of subxiphoid robot-assisted extended thymectomy (SRAET) and video-assisted thoracoscopic extended thymectomy (VATET) for myasthenia gravis complicated with thymoma. Methods    Retrospective analysis of 61 patients with myasthenia gravis combined with thymoma who were admitted to the Department of Thoracic Surgery, West China Hospital, Sichuan University from January 2017 to June 2019 was performed. All patients underwent extended thymectomy, and the patients were divided into a SRAET group and a VATET group. There were 26 patients in the SRAET group, including 11 males and 15 females, with an average age of 42.20±13.20 years. There were 35 patients in the VATET group, including 14 males and 21 females, with an average age of 45.00±13.00 years. The perioperative outcomes of the two groups including gender, age, operation time, intraoperative blood loss, conversion rate, postoperative drainage, tube removal time, drainage volume, visual analogue scale, hospital stay and postoperative complications were compared. Results    There was no conversion to thoracotomy, death or myasthenia crisis in both groups. The operation time (111.42±28.60 min vs. 103.71±26.20 min, P=0.845), intraoperative blood loss (32.31±23.84 mL vs. 63.57±132.22 mL, P=0.239), visual analogue scale at postoperative 24 h (2.46±0.76 vs. 2.40±0.74, P=0.751) and postoperative 48 h (2.12±0.77 vs. 2.26±0.56, P=0.407), complication rate (3.8%vs. 2.9%, P=0.675), drainage volume (206.85±130.09 mL vs. 276.86±173.46 mL, P=0.089) and hospital stay (5.81±2.52 d vs. 5.29±2.17 d, P=0.642) were not significantly different between the two groups. The visual analogue scale of the SRAET group at postoperative 72 h (1.12±0.65 vs. 1.86±0.91, P=0.001) was significantly lower than that of the VATET group. Conclusion    SRAET is a safe and feasible method with less postoperative short-term pain, which is an alternative surgical treatment for myasthenia gravis complicated with thymoma.

16.
Article in Chinese | WPRIM | ID: wpr-752259

ABSTRACT

Objective To investigate the characteristics of the phenylalanine hydroxylase( PAH)gene muta﹣tions in patients With phenylketonuria(PKU)in Guangxi region,in order to provide clinical data for genetic counseling and prenatal gene diagnosis. Methods Thirty-seven children diagnosed as PKU in the Maternal and Children's Hos﹣pital of Guangxi Zhuang Autonomous Region Were enrolled in the study betWeen January 2009 and December 2017. Ve﹣nous blood Was collected and the PAH gene sequence Was determined by Sanger sequencing after amplification With the polymerase chain reaction technique. The neW gene mutations Were defined based on the national and international literature revieW and databases. MeanWhile,100 healthy individuals Were selected as the control group for gene sequen﹣cing to confirm Whether the mutation Was a neW one. Results Thirty-seven cases of PKU Were detected for 68 muta﹣tions,With the detection rate being 91. 89%(68/74). Six mutations Were identified in exon 7,Which accounted for 31. 08% of all,exon 12(18. 92%),exon 8(10. 81%)and exon 6(10. 81%)folloWed. A total of 25 different muta﹣tions Were identified Which including 14 missense mutations(56. 00%),7 nonsense mutations(28. 00%),3 splicing junction mutations(12. 00%),and 1 deletion mutation(4. 00%). The most common mutations included c. 1223G>A (p. R408Q),c. 728G>A(p. R243Q)and c. 721C>T( p. R241C),accounting for 14. 86%,13. 51%,and 10. 81%, respectively. After querying international databases,including PAH mutation database and Human Gene Mutation Data﹣base and forecasting softWare,three kinds of mutations c. 314C> T(p. T105I),c. 583A> G(p. K195E),c . 851G>A(p. C284Y)Were verified as novel PAH gene mutations. Conclusions The mutation spectrum of the PAH gene in Guangxi has been identified. And 3 kinds of mutations have been identified. This may accumulate valuable information for gene diagnosis and prenatal diagnosis of PKU in Guangxi region.

17.
Article in Chinese | WPRIM | ID: wpr-744104

ABSTRACT

Methyl (S)-4-(6-amino-9H-purin-9-yl)-2-hydroxybutanoate (DZ2002) is a potent reversible inhibitor of S-adenosyl-L-homocysteine hydrolase (SAHH). Due to its ester structure, DZ2002 is rapidly hydrolyzed in rat blood to 4-(6-amino-9H-purin-9-yl)-2-hydroxybutyric acid (DZA) during and after blood sampling from rats; this hampers accurate determination of the circulating DZ2002 and its acid metabolite DZA in rats. To this end, a method for determining the blood concentrations of DZ2002 and DZA in rats was developed by using methanol to immediately deactivate blood carboxylesterases during sampling. The newly developed bioanalytical assay possessed favorable accuracy and precision with lower limit of quantification of 31 nM for DZ2002 and DZA. This validated assay was applied to a rat pharmacokinetic study of DZ2002. After oral administration, DZ2002 was found to be extensively converted into DZA. The level of systemic exposure to DZ2002 was significantly lower than that of DZA. The apparent oral bioavailability of DZ2002 was 90%–159%. The mean terminal half-lives of DZ2002 and DZA were 0.3–0.9 and 1.3–5.1 h, respectively. The sample preparation method illustrated here may be adopted for de-termination of other circulating ester drugs and their acid metabolites in rodents.

18.
Article in Chinese | WPRIM | ID: wpr-743425

ABSTRACT

Objective · To investigate the effect of Toll-like receptor 4 (TLR4) in the pathological injury in fat embolism mice model. Methods · One hundred and twenty male C57BL/6 mice were randomly divided into 10 groups. One group was set as blank control group, and others were injected separately with 1, 2…9 μL/g of allogeneic perirenal fat via tail vein, respectively. The mortality of each group was counted, median lethal dose (LD50) of fat injection in mice was calculated by Bliss method, and the fat embolism LD50 mice model was established. The TLR4 protein expression in the pulmonary tissue of surviving mice was detected by Western blotting. Sixty male C57BL/6 mice were randomly divided into the control group (the same dose of saline was given via tail vein) and the experimental groups (group 2 h, group 8 h, group 24 h and group 48 h, the LD50 fat was given via tail vein).The TLR4 protein expression at different time after fat injection was detected by Western blotting. The mortality of 20 TLR4 gene-knockout mice (TLR4-/-mice) was recorded and compared with 60 wild-type mice after LD50 fat injection. Results · The LD50 of fat embolism mice model was (3.93±0.78) μL/g.After the injection of 1-7 μL/g fat, the expressions of TLR4 protein in the pulmonary tissue of all seven groups were significantly increased, compared with the control group (all P=0.000). In the fat embolism LD50 mice model, compared with the control group, the expressions of TLR4 protein in group2 h were significantly increased (P=0.005). Then, expression level of TLR4 protein was gradually reduced after 2 h, and there was no significant difference between the control group and group 48 h. The mortality of TLR4-/- mice injected with LD50 fat was lower than that of wild-type mice (P=0.043).Conclusion · TLR4 protein involves in the pathologic process of fat embolism syndrome. The knockout of TLR4 gene can reduce the mortality of fat embolism mice. TLR4 and its correlated non-infectious inflammatory response may be an important molecular mechanism of biochemical injury in fat embolism syndrome. Blocking the activation of TLR4-mediated signaling pathway can significantly improve the prognosis, which provides new basis for the prevention, evaluation and treatment of fat embolism syndrome.

19.
Journal of Experimental Hematology ; (6): 1774-1778, 2019.
Article in Chinese | WPRIM | ID: wpr-781398

ABSTRACT

OBJECTIVE@#To investigate the clinical characteristics, etiology and drug susceptibility of bacterial bloodstream infections in acute leukemia(AL) patients.@*METHODS@#Clinical data, etiology and drug susceptibility of acute leukemia patients with bacterial bloodstream infections from April 2009 to April 2018 were retrospectively analyzed.@*RESULTS@#A total of 376 strains were isolated, 76.9% was Gram-negative bacterial and 23.1% was Gram-positive bacteria. Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae were listed as the top three of Gram-negative bacteria. The susceptibility of Escherichia coli to the tigacycline, imipenem and meropenem was 100.0%, 98.2% and 98.1%, respectively. The susceptibility of Klebsiella pneumoniae to the tigacycline, imipenem and meropenem were 100.0%, 98.3% and 94.4%, respectively. The adjustment rate for initial use of carbopenems was 3.8%, while the adjustment rate for initial use of noncarbopenems was 74.3% in patients with main Gram-negative bacterial blood stream infection. The susceptibility of Gram-positive bacteria to glycopeptide antibiotics, linezolid and tigacycline was 100.0%.@*CONCLUSION@#Gram-negative bacteria is the majority type of bacteria in AL patients with bacteria blood stream infections. The susceptibility of Gram-negative bacteria to the carbapenems is high, and the treatment adjustment rate is obviously low. The glycopeptide, linezolid and tigacycline are effective for Gram-positive bacteria infections..


Subject(s)
Bacteremia , Gram-Negative Bacteria , Gram-Positive Bacteria , Humans , Microbial Sensitivity Tests , Retrospective Studies
20.
Journal of Experimental Hematology ; (6): 1786-1793, 2019.
Article in Chinese | WPRIM | ID: wpr-781396

ABSTRACT

OBJECTIVE@#To investigate the effect of reactive oxygen species (ROS) on GDC-0152-induced apoptosis and autophagy of acute promyelocytic leukemia cell line NB4.@*METHODS@#Different concentrations of GDC-0152 combined with Z-VAD-FMK was applied to NB4 cells. Cell proliferation was detected by CCK8 method. Apoptosis rate, autophagy and ROS level were detected by flow cytometry. The autophagy was observed by Cyto-ID staining fluorescence microscopy, and flow cytometry were used to detect the fluorescence expression. The expression of autophagy-related protein LC3B was detected by Western blot.@*RESULTS@#GDC-0152 increased proliferation inhibition rate and apoptosis rate in NB4 cells (P<0.05); GDC-0152 induced increase of ROS level of NB4 cells; GDC-0152 increased autophagy of NB4 cells that was found by Cyto-ID staining fluorescence microscopy and flow cytometry (P<0.05). Western blot showed that GDC-0152 increased LC3B expression in NB4 cells and promoted the conversion of LC3BI to LC3BII; as compared with GDC-0152 (100 ng/ml), GDC-0152 (100 ng/ml) combined with ROS inhibitor YCG063 (10 μmol/L) decreased apoptosis and autophagy (P<0.05).@*CONCLUSION@#GDC-0152 inhibits cell proliferation by inducing apoptosis and autophagy of NB4 cells. ROS can promote GDC-0152-induced apoptosis and autophagy of NB4 cells.


Subject(s)
Apoptosis , Autophagy , Cell Line, Tumor , Cyclohexanes , Humans , Leukemia, Promyelocytic, Acute , Pyrroles , Reactive Oxygen Species
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