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1.
International Eye Science ; (12): 1361-1364, 2022.
Article in Chinese | WPRIM | ID: wpr-935013

ABSTRACT

Conbercept is a novel anti-vascular endothelial growth factor drug independently developed by China. Since it was approved for clinical application by the State Food and Drug Administration of China in 2013, conbercept has shown reliable safety and efficacy in the treatment of ocular neovascular diseases such as wet age-related macular degeneration, choroidal neovascularization and macular edema. For different diseases, the treatment strategies of conbercept are different. This article mainly reviews the application progress of conbercept in ocular neovascularization related diseases including wet age-related macular degeneration, diabetic macular edema, pathologic myopia choroidal neovascularization, neovascular glaucoma, retinopathy of prematurity and corneal neovascularization, and summarizes and explores the indications, administration scheme and therapeutic effect of conbercept. It is expected that the indications of conbercept will be wider and the administration scheme will be more given, and the usage of conbercept will bring new ideas for the treatment of ocular neovascular diseases.

2.
Chinese Journal of Hematology ; (12): 247-254, 2022.
Article in Chinese | WPRIM | ID: wpr-929565

ABSTRACT

Objective: This study aimed to explore the prognostic value of the revised international prognostic scoring system (IPSS-R) and the WHO prognostic scoring system (WPSS) in patients with myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: The clinical data of 184 patients with MDS who received allo-HSCT from July 2016 to June 2019 were retrospectively analyzed. IPSS-R and WPSS were performed at diagnosis and before transplantation. The prognostic values of IPSS-R and WPSS and potential risk factors were explored. Results: With a median follow-up of 21.9 (0.5-47.5) months, the two-year overall survival (OS) and progression-free survival (PFS) rates were (75.1±3.4)% and (71.6±3.6)% , respectively. The two-year cumulative relapse rate and nonrelapse mortality rate were (11.9±0.1)% and (16.5±0.1)% , respectively. There were no significant differences in OS and PFS between the IPSS-R ≤3.5 and >3.5 groups at diagnosis (P=0.409; P=0.724). No significant differences in OS and PFS between the WPSS ≤2 and >2 groups (P=0.426; P=0.726) were observed as well. When the patients were reevaluated before transplantation, the OS and PFS of the IPSS-R ≤3.5 group were significantly better than >3.5 group [OS: (88.6±4.1)% vs (65.8±5.3)% , P=0.003; PFS: (87.6±4.2)% vs (60.5±5.8)% , P=0.002]. However, there were no significant differences in OS and PFS among the WPSS ≤2 and >2 groups (P=0.584; P=0.565). In addition, the OS and PFS of the improved group based on IPSS-R were significantly better than those of the unimproved group before transplantation [OS: (83.8±4.6)% vs (69.3±5.8)% , P=0.027; PFS: (82.8±4.4)% vs. (64.0±7.2)% , P=0.006]. Multivariate analysis indicated that a pretransplant IPSS-R of >3.5 (P=0.021, HR=2.510, 95% CI 1.151-5.476) and TP53 mutation (P=0.047, HR=2.460, 95% CI 1.014-5.971) were independent risk factors for OS, whereas a pretransplant IPSS-R of >3.5 (P=0.017, HR=2.457, 95% CI 1.175-5.141) and pretransplant cytogenetic poor and very poor (P=0.008, HR=2.765, 95% CI 1.305-5.856) were independent risk factors for PFS. Conclusion: A pretransplantation evaluation of IPSS-R could help determine the prognosis of patients with MDS undergoing allo-HSCT. In addition, patients with improved IPSS-R scores before undergoing allo-HSCT had a better prognosis.


Subject(s)
Hematopoietic Stem Cell Transplantation , Humans , Myelodysplastic Syndromes/therapy , Prognosis , Retrospective Studies , Risk Factors
3.
Article in English | WPRIM | ID: wpr-928566

ABSTRACT

OBJECTIVES@#To study the change in asymmetric dimethylarginine (ADMA) in the circulation system of full-term infants with persistent pulmonary hypertension of the newborn (PPHN) and its association with treatment response, as well as the possibility of ADMA as a therapeutic target and a marker for treatment response.@*METHODS@#A prospective study was performed. A total of 30 full-term neonates who were diagnosed with PPHN within 3 days after birth were enrolled as the PPHN group, and the neonates without PPHN, matched for gestational age and age, who were treated or observed in the department of neonatology were enrolled as the control group. Serum samples were collected on days 1, 7, and 14 of treatment. The high-performance liquid chromatography-tandem mass spectrometry was used to measure the serum concentrations of L-arginine, ADMA, and its isomer symmetric dimethylarginine (SDMA).@*RESULTS@#For the neonates in the control group, the serum concentrations of ADMA and L-arginine continuously increased and the serum concentration of SDMA continuously decreased within the first 14 days of treatment. On days 1 and 14, there was no significant difference in the serum concentration of ADMA between the control and PPHN groups (P>0.05). On day 7, the PPHN group had a significantly higher serum concentration of ADMA than the control group (P<0.05), while there were no significant differences in serum concentrations of SDMA or L-arginine (P>0.05). Moreover, after 7 days of treatment, the PPHN neonates with a systolic pulmonary arterial pressure (sPAP) of >35 mmHg had a significantly higher serum concentration of ADMA than those with an sPAP of ≤35 mm Hg.@*CONCLUSIONS@#There are continuous increases in the ADMA concentration and the ADMA/SDMA ratio in the circulation system of full-term infants within the first 2 weeks after birth, and this process is accelerated by the pathological process of PPHN, suggesting that ADMA may be involved in the pathologic process of PPHN. A high level of ADMA is associated with the resistance to PPHN treatment, suggesting that inhibition of ADMA might be a potential target of drug intervention to improve the treatment response of PPHN.


Subject(s)
Arginine/analogs & derivatives , Biomarkers , Humans , Hypertension, Pulmonary/drug therapy , Infant, Newborn , Prospective Studies
4.
Article in Chinese | WPRIM | ID: wpr-905242

ABSTRACT

Objective:To analyze the effects of proprioceptive neuromuscular facilitation (PNF) on balance, motor and activities of daily living (ADL) for stroke patients. Methods:The randomized controlled trials about the effects of PNF on motor, balance and ADL in stroke patients were retrieved from PubMed, Embase, CNKI, Wanfang data, and VIP, since establishment to December, 2019. The primary outcome measures were Berg Balance Scale (BBS), Fugl-Meyer Assessment (FMA) and modified Bathel Index (MBI). The secondary outcome measures were Functional Reach Test (FRT), Trunk Impairment Scale (TIS), and Timed 'Up and Go' Test (TUGT). The literatures were independently screened by two investigators, and the quality of the articles was evaluated using the Cochrane Library systematic review criteria, and meta-analysis was performed using RevMan 5.3. Results:A total of 13 articles were included with 786 stroke patients. PNF increased the score of BBS for sequelae patients (MD = 3.31, 95%CI 2.58 to 4.04, P < 0.001), FMA for recovery patients (MD = 8.31, 95%CI 5.68 to 10.97, P < 0.001); as well as MBI score (MD = 6.84, 95%CI 5.20 to 8.48, P < 0.001), FRT distance (MD = 1.11, 95%CI 0.39 to 1.84, P = 0.003) and TIS score (MD = 1.75, 95%CI 1.19 to 2.31, P < 0.001) for all the patients, and decreased TUGT time for sequelae patients (MD = -1.86, 95%CI -2.62 to -1.10, P < 0.001). Conclusion:PNF can significantly improve balance, motor and ADL for stroke patients. The effectiveness is various with the course of disease. More high-quality researches are needed.

5.
Article in Chinese | WPRIM | ID: wpr-905210

ABSTRACT

Objective:To explore the effects of home-based telerehabilitation guidance on physical function and activities of daily living for stroke patients. Methods:From September, 2015 to March, 2018, 240 stroke recovering patients from three community health service centers in Fengtai District, Beijing for outpatient rehabilitation were randomly divided into control group (n = 120) and tele-rehab group (n = 120). Both groups accepted routine rehabilitation for six months, while the tele-rehab group received telerehabilitation guidance in addition. They were assessed with Fugl-Meyer Assessment (FMA) and modified Barthel Index (MBI) before and after treatment. Results:The scores of FMA and MBI improved after treatment in both groups (|t| > 14.536, P < 0.001), and improved more in the tele-rehab group than in the control group (|t| > 2.200, P < 0.05). Conclusion:Home-based telerehabilitation guidance may enhance the effect of community-based outpatient rehabilitation for stroke patients.

6.
Article in Chinese | WPRIM | ID: wpr-905145

ABSTRACT

Objective:To explore the effects of bilateral arm transcutaneous electrical acupoint stimulation (TEAS) based on mirror therapy (MT) on upper limb function of subacute stroke hemiplegic patients. Methods:From September, 2017 to October, 2019, 48 subacute stroke hemiplegic patients were randomly divided into control group (n = 24) and experimental group (n = 24). All the patients accepted routine rehabilitation and MT, while the experimental group received bilateral arm TEAS and the control group received sham TEAS, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremity (FMA-UE), Action Research Arm Test (ARAT), Wolf Motor Function Test (WMFT) and modified Barthel Index (MBI) before and after treatment. Results:All the scores of FMA-UE, ARAT, WMFT and MBI improved in both groups after treatment (|t| > 11.870, P < 0.001), and improved more in the experimental group than in the control group (|t| > 2.678, P < 0.05). Conclusion:Bilateral arm TEAS based on MT can promote the upper limb function of subacute stroke hemiplegic patients.

7.
Chinese Journal of School Health ; (12): 109-111, 2021.
Article in Chinese | WPRIM | ID: wpr-862607

ABSTRACT

Objective@#To investigate the effects of orthokeratology lenses and frame glasses on anisometropia in children with low myopia in one eye.@*Methods@#Between January 2017 and January 2018, 120 children of primary and secondary school age with myopic anisometropia low myopia in one eye presenting to the Second People s Hospital of Yunnan Province were selected as research objects,with average refractive error of(-1.00,-2.50)D in one eye and(-0.50,0.50)D in another eye. Participants were divided into an experimental group and a control group (60 cases per group), according to a random number grouping method. The control group were given frame glasses, while the experimental group were given orthokeratology lenses. A prospective study was conducted to compare and analyze the lengths of the posterior eye axis (AL) and spherical equivalent (SE), measured at different time intervals between the two groups.@*Results@#There were some initial differences in AL and SE between the two groups before the experiment began; however, this difference was not statistically significant (P>0.05). After 12 months, participants myopic eyes given the orthokeratology lenses had shorter AL[(24.91±0.11)mm] compared to the control group[(25.02±0.09)mm],participants health eyes had longer AL[(24.58±0.24)mm] compared to the control group[(24.20±0.13)mm]. One month after the subjects stopped wearing plastic mirrors,participants myopic eyes had higher SE[(-2.22±0.78)D] compared to the control group[(-2.64±0.21)D],and had lower that in the control group[(-0.96±0.84)(-0.37±0.54)D](t=4.02,-4.58,P<0.05).@*Conclusion@#In children with low myopia in one eye, compared with wearers of frame glasses, wearing corneal shape lenses can effectively restrain AL extend and control the progression of eye myopia. At the same time, wearing corneal shape lenses can promote contralateral healthy eye axial extension and an increase in diopter, reduce the anisometropia value, solve the problems of a binocular visual axis development imbalance, and promote coordinated eye development.

8.
Article in Chinese | WPRIM | ID: wpr-864386

ABSTRACT

Objective:To explore the influence of neonatal intensive care unit (NICU) environmental factors on physiological function of premature infants, and propose improvement plan.Methods:A total of 40 cases of low body mass premature infants from June to December in 2017 in Chongqing Center for Women and Children were selected as the research objects, and 8:00-9:00 of working day was set as the daily period, 10:00-11:00 as the quiet period. Light, sound, touch and other environmental factors in NICU were detected quantitatively, basic vital signs, activity, stress hormones and other changes were recorded, and the impact of environmental factors on the children was analyzed.Results:Touch times in daily and quiet periods were (5.02±0.54) times/h and (4.56±0.55) times/h, with no significant difference ( P>0.05). The same time as the next two days, the activity of premature infants in quiet period was (8.26±3.10), which was lower than that in daily period (17.52±5.78), and the difference was statistically significant ( t value was 8.967, P<0.01). The sleep time of premature infants during quiet period (23.24±8.38) was significantly higher than that of daily period (4.80 ±5.39), the difference was statistically significant ( t value was-11.679, P<0.01). The levels of cortisol, epinephrine and norepinephrine in premature infants were (61.53±13.47), (15.91±3.94), (49.22±15.15) μg/L in quiet period, which were significantly lower than those in daily period (74.52±20.98), (23.40±11.66), (80.32±32.43) μg/L ( t value was 3.295, 3.848, 5.502, P<0.01). The heart rate and systolic pressure of premature infants in quiet period (130.44±8.06) beats/min, (64.05±10.40) mmHg (1 mmHg=0.133 kPa) were significantly lower than those in daily period (145.21±10.52) beats/min, (72.85±13.36) mmHg, and the difference was statistically significant ( t value was 3.340, 2.166, P<0.01 or 0.05). Different time periods on the same day, the activity of premature infants in quiet period was (9.87±3.31), which was lower than that in daily period (19.82±5.57), and the difference was statistically significant ( t value was 9.761, P<0.01). The sleep time of premature infants during quiet period (25.75±9.07) was significantly higher than that of daily period (4.70±3.89), the difference was statistically significant ( t value was-13.457, P<0.01). The levels of cortisol, epinephrine and norepinephrine in premature infants were (59.42±11.95), (15.78±1.45), (50.90±14.73) μg/L in quiet period, which were significantly lower than those in daily period (71.50±20.56), (25.62±11.95), (79.87±29.91) μg/L ( t value was 3.212, 5.169, 3.585, P<0.01). The heart rate and systolic pressure of premature infants in quiet period (136.02±11.22) beats/min, (65.35±9.56) mmHg were significantly lower than those in daily period (144.10±9.18) beats/min, (73.47±12.92) mmHg, and the difference was statistically significant ( t value was 3.533, 2.008, P<0.01 or 0.05). Conclusions:Children with NICU are generally in high noise and strong light environment, these factors will cause adverse physiological reactions to a certain extent.

9.
Article in Chinese | WPRIM | ID: wpr-799792

ABSTRACT

Objective@#To explore the influence of neonatal intensive care unit (NICU) environmental factors on physiological function of premature infants, and propose improvement plan.@*Methods@#A total of 40 cases of low body mass premature infants from June to December in 2017 in Chongqing Center for Women and Children were selected as the research objects, and 8:00-9:00 of working day was set as the daily period, 10:00-11:00 as the quiet period. Light, sound, touch and other environmental factors in NICU were detected quantitatively, basic vital signs, activity, stress hormones and other changes were recorded, and the impact of environmental factors on the children was analyzed.@*Results@#Touch times in daily and quiet periods were (5.02±0.54) times/h and (4.56±0.55) times/h, with no significant difference (P>0.05). The same time as the next two days, the activity of premature infants in quiet period was (8.26±3.10), which was lower than that in daily period (17.52±5.78), and the difference was statistically significant (t value was 8.967, P<0.01). The sleep time of premature infants during quiet period (23.24±8.38) was significantly higher than that of daily period (4.80 ±5.39), the difference was statistically significant (t value was-11.679, P<0.01). The levels of cortisol, epinephrine and norepinephrine in premature infants were (61.53±13.47), (15.91±3.94), (49.22±15.15) μg/L in quiet period, which were significantly lower than those in daily period (74.52±20.98), (23.40±11.66), (80.32±32.43) μg/L (t value was 3.295, 3.848, 5.502, P<0.01). The heart rate and systolic pressure of premature infants in quiet period (130.44±8.06) beats/min, (64.05±10.40) mmHg (1 mmHg=0.133 kPa) were significantly lower than those in daily period (145.21±10.52) beats/min, (72.85±13.36) mmHg, and the difference was statistically significant (t value was 3.340, 2.166, P<0.01 or 0.05). Different time periods on the same day, the activity of premature infants in quiet period was (9.87±3.31), which was lower than that in daily period (19.82±5.57), and the difference was statistically significant (t value was 9.761, P<0.01). The sleep time of premature infants during quiet period (25.75±9.07) was significantly higher than that of daily period (4.70±3.89), the difference was statistically significant (t value was-13.457, P<0.01). The levels of cortisol, epinephrine and norepinephrine in premature infants were (59.42±11.95), (15.78±1.45), (50.90±14.73) μg/L in quiet period, which were significantly lower than those in daily period (71.50±20.56), (25.62±11.95), (79.87±29.91) μg/L (t value was 3.212, 5.169, 3.585, P<0.01). The heart rate and systolic pressure of premature infants in quiet period (136.02±11.22) beats/min, (65.35±9.56) mmHg were significantly lower than those in daily period (144.10±9.18) beats/min, (73.47±12.92) mmHg, and the difference was statistically significant (t value was 3.533, 2.008, P<0.01 or 0.05).@*Conclusions@#Children with NICU are generally in high noise and strong light environment, these factors will cause adverse physiological reactions to a certain extent.

10.
Article in Chinese | WPRIM | ID: wpr-774366

ABSTRACT

OBJECTIVE@#To investigate the mechanism of Paris forrestii (Takht.) H. Li (PCT3)-suppressing the proliferation of HL-60, K562, KG-1 and HT-93 cells.@*METHODS@#cute myeloid leukemia cell lines such as HL-60, K562, KG-1 and HT-93 were treated with Paris forrestii (Takht.) H. Li (PCT3) for 24, 48, and 72 h, and MTT assay was employed to determine the cells proliferation. Meanwhile, the apoptosis of K562, HL-60, KG-1 and HT-93 cells were detected by flow cytometry after PCT3 (Control, 4 μg/ml, 8 μg/ml) treated for 24 h and the Western blot was performed to detect the expression of PARP,Caspase-3, MCL-1, BAX, BCL-2, P53, and P27. GAPDH was used as an internal loading control.@*RESULTS@#MTT assay showed that Paris forrestii (Takht.) H. Li (PCT3) significantly inhibited the proliferation of HL-60, K562, KG-1 and HT-93 cells in concentration and time-dependent manners. Compared with the control group, the leukemia cell viabilities were significantly suppressed (r =0.9436; r =0.8623; r =0.9922; r =0.8918). Paris forrestii (Takht.) H. Li (PCT3) induced apoptosis of leukemia cells in a concentration dependent manner, compared with the control group (P<0.05 or P<0.01). Western blot revealed that PARP, a major enzyme in DNA damage repair, and Caspase-3 another one of the major executive apoptotic enzymes were cleaved in cell lines examined, and this cleavage was concentration dependent. Anti-apoptotic proteins such as MCL-1 and BCL-2 were down regulated by Paris forrestii (Takht.) H. Li (PCT3), and Pro-apoptotic protein BAX was upregulated. And the protein of tumor suppressor gene P53 and its downstream signaling protein P27 increased.@*CONCLUSION@#Paris forrestii (Takht.) H. Li (PCT3) can inhibit the proliferation of leukemia cells by activating endogenous apoptosis pathway, and provide a potential new drug selection for clinical treatment of AML leukemia.


Subject(s)
Apoptosis , Caspase 3 , Cell Line, Tumor , Cell Proliferation , Humans , Leukemia, Myeloid, Acute , Melanthiaceae , Proto-Oncogene Proteins c-bcl-2
11.
Article in Chinese | WPRIM | ID: wpr-774328

ABSTRACT

OBJECTIVE@#To investigate the gene mutation of patients with WAS gene defect and its correlation with clinical manifestations.@*METHODS@#Thirty-one patients consulted in Children's Hospital of Soochow University from January 2013 to February 2018 were enrolled in this study. The hot pot mutations of WAS gene in 31 patients were detected and related clinical phenotypes were analyzed retrospectively.@*RESULTS@#All patients were male. The median onset age was 1 month (range, 0-83 months). Nine mutants were reported as novel mutations among 25 mutants detected in 31 patients, including c.1234_1235dupCC, c.1093-1097delG, c.28-30dupC, c.436G>T, c.273 + 10_273 + 11dupCC, c.995_996insG, c.1010T>A, c.332_333delCC and c.683C>T mutations. There were 25 cases of classic WAS which mutations included missense mutation, deletion mutation, insertion mutation, splicing mutation and nonsense mutation, 2 cases of X-linked thrombocytopenia (XLT) were induced by missense mutation, 1 case of intermittent X-linked thrombocytopenia (IXLT) was induced by splicing mutation, 2 cases of X-linked pancytopenia were induced by missense mutation. Intravenous immunoglobulin (IVIG) and glucocorticoid therapy in IXLT patient was effective, and remission could be sustained, platelets could be increased in the short-term in treated XLT patients, but only a small part of classic WAS patients(8.0%) showed transient response to it, the IVIG and glucocorticoid therapy did not improve the status of platelet in XLP patients. Immune laboratory examination showed that CD3 was decreased in 60.0% patients, CD19 was decreased in 12.0% patients, and CD56CD16 in 4 patients was decreased, accounting for 16.0%. Out of 24 patients, 22 patients were alive after treated with hematopoietic stem cell transplantation (HSCT), 4 patients who were not given HSCT died of brain bleeding and severe infection, 1 patient diagnosed as IXLT got remission and survived.@*CONCLUSION@#WAS gene defect is an important basis for the diagnosis of WAS and related diseases. IVIG plus glucocorticoid therapy is less effective for fewer patients, the HSCT is an effective treatment for WAS.


Subject(s)
Genetic Diseases, X-Linked , Humans , Male , Mutation , Phenotype , Retrospective Studies , Thrombocytopenia , Wiskott-Aldrich Syndrome Protein , Genetics
12.
Acta Pharmaceutica Sinica ; (12): 220-226, 2018.
Article in Chinese | WPRIM | ID: wpr-779866

ABSTRACT

The study is aimed to investigate the anti-depressant effect of puerarin in rat model of depression induced by chronic unpredictable mild stress (CUMS) and to explore the relevant mechanism. We established the depression rat model using CUMS. Rats were randomly divided into control, CUMS model, CUMS +fluoxetine (10 mg·kg-1) and CUMS +puerarin (50, 100, 200 mg·kg-1) groups. Drugs or vehicle were administrated after stress induction for 21 days. Open-field test (OFT), sucrose preference tests (SPT) and forced swim test (FST) were used to evaluate the anti-depressant effects of puerarin. The reactive oxygen species (ROS), prostaglandin E2 (PGE2) level, superoxide dismutase (SOD) and catalase (CAT) activities in hippocampus were determined by ELISA. Expression of IL-1β, TNF-α, and IL-10 was measured by qRT-PCR and Western blot analysis. Behavioral test suggests that crossing score, rearing score in OFT and sucrose preference index in SPT of model group were significantly lower than the control group (PP2 level increased significantly (PPβ, TNF-α, and IL-10 were increased significantly (PP< 0.01) in rats of CUMS. Puerarin and fluoxetine ameliorated those changes induced by CUMS. Puerarin improved the depression-like behaviors of rats induced by CUMS, and the mechanism may involve in the antioxidant and anti-inflammatory effects.

13.
Journal of Forensic Medicine ; (6): 659-664, 2018.
Article in Chinese | WPRIM | ID: wpr-742815

ABSTRACT

Due to the concealment and incidence higher than reported statistics, infanticide should attract the attention of legal medical experts.The infanticide process has common behavioral characteristics.The perpetrators are most frequently biological mothers who are unmarried, with inferior education, and lack of routine pregnancy tests.Medicolegal identification of infanticide cases includes identification of live births and causes of death.Besides the classical lung floating test, there are other methods to identify live births such as pulmonary interstitial emphysema, CT imaging examination, immunohistochemical examination of umbilical cord vitality markers.Neonatal line measurement is the only way to identify live births in corpse with severe decomposition.The main causes of death in infanticide are mechanic asphyxia and fatal head trauma.Shaken baby syndrome, as a common abusive head trauma, is pathologically characterized by the triad of encephalopathy, subdural haemorrhage (SDH) and retinal haemorrhage (RH).During the autopsy of suspected shaking baby syndrome, in addition to carefully examining cervical cord, the possibility of pathological temporal lobe hemorrhage should also be ruled out.

14.
Article in Chinese | WPRIM | ID: wpr-705268

ABSTRACT

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the accu-mulation of immature myeloid progenitor cells in the bone marrow,compromising of normal hematopoi-esis and ultimately resulting in bone marrow failure. Chemotherapy is the mainstay treatment for all AML patients,however,drug resistance and clinical relapse limits its efficacy.The 5-year survival rate of AML patients is only 26.6%.Survival rates are even lower among patients ages 65 to 74 years (5.3%)and 75 years or older(1.6%).Therefore,exploring novel therapeutic agents is urgent for improving the outcome of patients with AML. Saponins are amphipathic glycosides found in traditional Chinese medicines. In the present study, we isolated a panel of saponins from Paris forrestii (Takht.) H. Li, a unique plant found in Tibet and Yunnan provinces, China. By examining their activities in suppressing acute myeloid leukemia cell proliferation, total saponins from Paris forrestii (TSPf) displayed more potent activity than individual ones.TSPf induced more than 40% AML cell apoptosis within 24 h and decreased the viability of all leukemia cell lines. TSPf-induced apoptosis was confirmed by both Annexin V staining and caspase-3 activation.TSPf downregulated pro-survival proteins Mcl-1,Bcl-xL and Bcl-2,but upreg-ulated the expression of tumor suppressor proteins p53,p27,Bax and Beclin 1.The AKT/mTOR signaling pathway is frequently over activated in various AML cells,and TSPf was found to suppress the activa-tion of both AKT and mTOR,but had no effects on their total protein expression.This was further con-firmed by the inactivation of 4EBP-1 and p70S6K,two typical downstream signal molecules in the AKT/mTOR pathway. More specifically, TSPf-inactivated AKT/mTOR signaling was found to be associated with downregulated RNF6, a recently identified oncogene in AML. RNF6 activated AKT/mTOR, and consistently, knockdown of RNF6 led to inactivation of the AKT/mTOR pathway. Furthermore, TSPf suppressed the growth of AML xenografts in nude mice models. Oral administration of 100 mg·kg-1 body weight almost fully suppressed tumor growth within 14 d, without gross toxicity. This study thus demonstrated that TSPf displays potent anti-AML activity by suppressing the RNF6/AKT/mTOR pathway. Given its low toxicity,TSPf could be developed for the treatment of AML.

15.
Article in Chinese | WPRIM | ID: wpr-701204

ABSTRACT

AIM:To investigate the mechanism of angiotensinⅡ(AngⅡ)/angiotensinⅡ type 1 receptor (AT1R)pathway activating protein phosphatase 2A(PP2A)which leads to down-regulation endothelial nitric oxide syn-thase(eNOS)phosphorylation level in mesenteric arteries of rats.METHODS: METHODS: The mesenteric arteries of adult male SD rats(weighing 160~180 g;n=90)were isolated under aseptic conditions.Firstly,to determine the effect of angiotensinⅡdown-regulated eNOS(Ser1177)phosphorylation level,the mesenteric arteries were randomly divided into normal control(control)group and AngⅡgroup.The mesenteric arteries in AngⅡgroup were incubated with AngⅡat 1×10 -7mol/L,1×10 -6mol/L and 1×10 -5mol/L for 6 h,12 h and 24 h,respectively.Secondly,to investigate the mo-lecular mechanism by which angiotensinⅡ activated PP2A leading to down-regulation eNOS(Ser1177)phosphorylation level,the mesenteric arteries were randomly divided into control group, AngⅡ group and candesartan(CAN; a specific AT1R blocker)+AngⅡgroup.The mesenteric arteries were pretreated with 1×10 -5mol /L CAN for 1 h,then incubated with 1×10 -7mol/L AngⅡfor 12 h in CAN+AngⅡgroup.The protein levels of eNOS,p-eNOS(Ser1177),PP2Ac,p-PP2Ac(Tyr307)and protein phosphatase 2A inhibitor 2(IPP2A2 )in the arteries were determined by Western blot.The ac-tivity of PP2A in the arteries was detected by PP2A activity kit.RESULTS:Compared with the control group,the protein level of p-eNOS(Ser1177)in the mesenteric arteries was decreased after incubated with AngⅡfor 6 h,12 h and 24 h(P<0.05).The decreasing tendency of p-eNOS(Ser1177)showed concentration-dependently,especially in 12 h and 24 h groups.The expression of eNOS protein showed no significant difference in each group.Compared with the control group, the mesenteric arteries of the rats were incubated with AngⅡ at 1×10-7mol/L for 12 h in vitro, the protein levels of p-eNOS(Ser1177)were down-regulated(P<0.05); pretreatment with CAN significantly increased the protein level of p-eNOS(Ser1177)(P<0.05);the protein levels of eNOS showed no significant difference in each group.Compared with the control group,the protein levels of p-PP2Ac(Tyr307)and IPP2A2 were decreased after the mesenteric arteries were trea-ted with AngⅡat 1×10 -7mol/L for 12 h(P<0.05).Candesartan pretreatment restored the protein levels of p-PP2Ac (Tyr307)and IPP2A2 (P<0.05),however the expression of PP2Ac protein showed no significant difference in each group. Compared with the control group,the activity of PP2A was increased in the mesenteric arteries incubated with AngⅡat 1× 10-7mol/L for 12 h(P<0.05).Candesarten pretreatment inhibited the activity of PP 2A significantly(P<0.05).CON-CLUSION:AngⅡincreases PP2A activity via AT1R pathway,thus leading to down-regulation eNOS(Ser1177)phospho-rylation level in mesenteric arteries.The molecular mechanism of PP2A activation may be associated with decreasing the protein levels of p-PP2Ac(Tyr307)and IPP2A2.

16.
Article in Chinese | WPRIM | ID: wpr-695697

ABSTRACT

Objective· To prepare nanobowls,establish the method for characterizing nanoparticles,and test drug loading efficiency and release efficiency of nanobowls.Methods · The polystyrene nanoparticles (PSNPs) were prepared by the means of the normal emulsion polymerization.The peanuts nanoparticles (PNPs) were synthesized by the swelling process of PSNPs and the selective crosslinking between 3-(trimethoxysilyl) propyl methacrylate and tetraethylorthosilicate.Finally,the polystyrene was dissolved to obtain nanobowls.Dynamic light scattering (DLS) was used to analyze the size of each kind of nanoparticles.Transmission electron microscope (TEM) was used to observe the morphology of nanoparticles.Nanobowls loaded doxorubicin hydrochloride as a model drug though continuous shaking were used to measure drug loading capacity and release efficiency.Results· PSNPs,coated polystyrene nanoparticles (CPSNPs),PNPs,silica peanuts nanoparticles (Si-PNPs) and nanobowls were synthesized successfully.The size of nanobowls was (126.7±4.9) nm and the Zeta potential was (-30.2±1.1) mV.The final nanoparitcles could be used to load drug easily.The drug loading efficiency and loading capacity reached 51.1% and 9.3%,respectively.Moreover,the nanobowls had the expected sustained release effect.Conclusion · The prepared nanobowls are loaded with drugs successfully,which can release drug slowly and almost completely.The nanobowls can be used for drug release delivery.

17.
Journal of Experimental Hematology ; (6): 1356-1361, 2017.
Article in Chinese | WPRIM | ID: wpr-301724

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the efficacy of CCCG-BNHL-2015 protocol in treatment of children with mature B-cell acute lymphoblastic leukemia (mature B-ALL).</p><p><b>METHODS</b>Seven pediatric patients with newly diagnosed mature B-ALL were treated by CCCG-BNHL-2015 protocol (risk group R4) in Children's Hospital of Nanjing Medical University from November 2014 to January 2017.</p><p><b>RESULTS</b>The median age of patients at initial diagnosis was 7.2 years (range 4.1 to 11.75 years) with a male predominance (5:2), the clinical characters were as follows: 4 cases combined with thoracic and/or abdominal lumps, only lymphonode was involved in 1 case, bone destruction was complicated in 2 cases and 1 case was complicated with central nervous system leukemia. In 2 children, tumor lysis syndrome appeared at early phase. The lactate dehydrogenase level at diagnosis of all patients extremely increased. All patients achieved complete remission after 2 to 4 courses of therapy. Two among them underwent autologous hematopoietic stem cell transplantation. One with primary central nervous system leukemia relapsed before the last course, then the treatment was abandoned. The rest of 6 patients survived with a median follow-up period of 14 months (ranged from 7 to 28 months), and suffered from different degrees of myelosuppression and infection. No one died from serious complications.</p><p><b>CONCLUSION</b>The CCCG-BNHL-2015 protocol (risk group R4) shows better curative effect, higher safety and remission rate in childhood mature B-cell lymphoblastic leukemia.</p>

18.
Article in Chinese | WPRIM | ID: wpr-300408

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the changes in the expression of EphA5 and its ligand ephrinA5 in the hippocampus of rats with epilepsy and their role in the pathogenesis of temporal lobe epilepsy (TLE).</p><p><b>METHODS</b>A total of 240 Sprague-Dawley rats were randomly divided into control group and TLE group, with 120 rats in each group. A rat model of lithium-pilocarpine TLE was established, and then the rats were divided into subgroups at 12 and 24 hours and 7, 15, 30, and 60 days after epilepsy was induced. In-situ hybridization was used to measure the mRNA expression of ephrinA5 in the CA3 region and the dentate gyrus of the hippocampus in 9 rats; immunohistochemistry was used to measure the protein expression of EphA5 in the CA3 region and the dentate gyrus of the hippocampus in 9 rats; Neo-Timm silver staining was used to observe mossy fiber sprouting in the CA3 region of the hippocampus in 2 rats.</p><p><b>RESULTS</b>In-situ hybridization showed mRNA expression of ephrinA5 in the CA3 region of the hippocampus, but this was not found in the dentate gyrus. Compared with the control group at the same time point, the TLE group had a significant reduction in the mRNA expression of ephrinA5 in the CA3 region of the hippocampus at 7 and 15 days after epilepsy was induced (P<0.05); at 30 and 60 days after epilepsy was induced, the TLE group had a gradual increase in the mRNA expression of ephrinA5 in the CA3 region of the hippocampus, and there was no significant difference between the TLE and control groups (P>0.05). Immunohistochemistry showed that EphA5 protein was expressed in the CA3 region and the dentate gyrus of the hippocampus and had a similar trend of change as ephrinA5 mRNA. Neo-Timm silver staining showed that the TLE group developed marked mossy fiber sprouting in the CA3 region of the hippocampus at 7 and 15 days after epilepsy was induced.</p><p><b>CONCLUSIONS</b>Downregulation of ephrinA5 and EphA5 in the CA3 region of the hippocampus may participate in the mechanism of mossy fiber sprouting and is closely associated with the development and progression of epilepsy.</p>


Subject(s)
Animals , Ephrin-A5 , Genetics , Physiology , Epilepsy, Temporal Lobe , Metabolism , Hippocampus , Chemistry , Male , RNA, Messenger , Rats , Rats, Sprague-Dawley , Receptor, EphA5 , Genetics , Physiology
19.
Article in Chinese | WPRIM | ID: wpr-660666

ABSTRACT

Objective · To investigate the effect of modified electroconvulsive therapy (MECT) on oxidative stress parameters in patients with bipolar disorder. Methods · Forty-three patients with bipolar disorder (case group) were enrolled that received MECT intervention for 6 weeks, and 49 healthy volunteers (control group) were recruited. Chinese versions of the 17 items Hamilton Depression Rating Scale (HAMD-17), Young Mania Rating Scale (YMRS) and Clinical Global Impression-Severity Scale (CGI-S) were used to assess the efficacy and side effects at baseline and after 6 weeks of treatment. The plasma levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured at baseline and after 6 weeks of treatment to assess the level of oxidative stress. Results · The serum MDA and GSH-Px levels of the case group were higher while the serum SOD levels of the case group was lower than that of the control group, and there was no significant difference in the serum CAT levels between two groups at baseline. MDA levels were higher in manic states than in depressed states, and they were positively correlated with the CGI-S scores. After MECT treatment, the CGI-S scores of patients decreased significantly, and the plasma MDA levels decreased significantly in manic and depressive states, but there was no change in other oxidative stress parameters. Conclusion · There was oxidative stress damage in patients with bipolar disorder, and the severity of the disease varied with the degree of damage. MECT improved the symptoms of the disease and decreased the level of plasma MDA, while there was no effect on the anti-oxidation index.

20.
Article in Chinese | WPRIM | ID: wpr-658009

ABSTRACT

Objective · To investigate the effect of modified electroconvulsive therapy (MECT) on oxidative stress parameters in patients with bipolar disorder. Methods · Forty-three patients with bipolar disorder (case group) were enrolled that received MECT intervention for 6 weeks, and 49 healthy volunteers (control group) were recruited. Chinese versions of the 17 items Hamilton Depression Rating Scale (HAMD-17), Young Mania Rating Scale (YMRS) and Clinical Global Impression-Severity Scale (CGI-S) were used to assess the efficacy and side effects at baseline and after 6 weeks of treatment. The plasma levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured at baseline and after 6 weeks of treatment to assess the level of oxidative stress. Results · The serum MDA and GSH-Px levels of the case group were higher while the serum SOD levels of the case group was lower than that of the control group, and there was no significant difference in the serum CAT levels between two groups at baseline. MDA levels were higher in manic states than in depressed states, and they were positively correlated with the CGI-S scores. After MECT treatment, the CGI-S scores of patients decreased significantly, and the plasma MDA levels decreased significantly in manic and depressive states, but there was no change in other oxidative stress parameters. Conclusion · There was oxidative stress damage in patients with bipolar disorder, and the severity of the disease varied with the degree of damage. MECT improved the symptoms of the disease and decreased the level of plasma MDA, while there was no effect on the anti-oxidation index.

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