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1.
Acta Pharmaceutica Sinica B ; (6): 421-432, 2019.
Article in English | WPRIM | ID: wpr-774977

ABSTRACT

Prodrug nanoassemblies, which can refrain from large excipients, achieve higher drug loading and control drug release, have been placed as the priority in drug delivery system. Reasoning that glutathione (GSH) and reactive oxygen species (ROS) are highly upgraded in tumor tissues which makes them attractive targets for drug delivery system, we designed and synthetized a novel prodrug which utilized mono thioether bond as a linker to bridge linoleic acid (LA) and docetaxel (DTX). This mono thioether-linked conjugates (DTX-S-LA) could self-assemble into nanoparticles without the aid of much excipients. The mono thioether endowed the nanoparticles redox sensitivity resulting in specific release at the tumor tissue. Our studies demonstrated that the nanoassemblies had uniform particle size, high stability and fast release behavior. DTX-S-LA nanoassemblies outperformed DTX solution in pharmacokinetic profiles for it had longer circulation time and higher area under curve (AUC). Compared with DTX solution, the redox dual-responsive nanoassemblies had comparable cytotoxic activity. Besides, the antitumor efficacy was evaluated in mice bearing 4T1 xenograft. It turned out this nanoassemblies could enhance anticancer efficacy by increasing the dose because of higher tolerance. Overall, these results indicated that the redox sensitivity nanoassemblies may have a great potential to cancer therapy.

2.
Article in English | WPRIM | ID: wpr-691383

ABSTRACT

<p><b>OBJECTIVE</b>To examine the efficacy and safety of bathing therapy with Taohong Siwu Decoction (, TSD) in the treatment of early-stage, mild-moderate diffuse cutaneous systemic sclerosis (dcSSc).</p><p><b>METHODS</b>This randomized, placebo-controlled trial enrolled 148 men and women (18-60 years) with dcSSc (disease duration 12 months) and baseline modified Rodnan skin score (MRSS) 10. Patients were randomized into a TSD group (71 cases bathing with TSD plus oral prednisone) or control group (71 cases bathing with placebo plus oral prednisone). Bathing (40 °C, 30 min) of the upper and lower limbs was carried out once daily for 12 consecutive weeks. The primary outcome measure was MRSS; secondary outcomes were Raynaud's phenomenon (RP) score, quality of life (QOL), physician visual analogue scale (VAS), patient VAS, percent predicted diffusing capacity for carbon monoxide (DLCO), percent predicted forced vital capacity (FVC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level and overall treatment effect.</p><p><b>RESULTS</b>The final analysis included 135 patients (control group, 68 cases; TSD group, 67 cases). Primary and secondary outcome measures after 2 weeks of treatment showed no improvement (versus baseline) in both groups, with no differences between groups. At 12 weeks, QOL, physician VAS, patient VAS, ESR and CRP were improved in both groups, but MRSS and RP score were improved only in the TSD group (all P<0.05). MRSS, RP score, QOL, physician VAS, patient VAS, ESR and CRP differed significantly between groups (all P<0.05). Meanwhile, the overall treatment effect was significantly higher in the TSD group than in the control group (P<0.05). Adverse events in the two groups were similar (P>0.05).</p><p><b>CONCLUSIONS</b>Bathing with TSD plus oral prednisone achieves better outcomes than oral prednisone alone in patients with dcSSc and is not associated with serious adverse events.</p>


Subject(s)
Adult , Drugs, Chinese Herbal , Therapeutic Uses , Female , Humans , Hygiene , Intention to Treat Analysis , Male , Middle Aged , Outcome Assessment, Health Care , Placebos , Scleroderma, Diffuse , Drug Therapy , Treatment Outcome
3.
International Eye Science ; (12): 1121-1123, 2018.
Article in Chinese | WPRIM | ID: wpr-695388

ABSTRACT

· AIM:To investigate the correlation between retinal thickness (CSRT) in the macular region and glycosylated hemoglobin (HbA1c) of patients with type 2 diabetes mellitus.· METHODS:Totally 39 cases of patients with diabetes (77 eyes) who screened from May 2016 to March 2017 were selected,and were divided into two groups according to the levels of HbA1c,which the 24 cases (47 eyes) in the low HbA1c group (HbA1c<8%) and 15 cases (30 eyes) in high HbA1c group (HbA1c≥8%).Other 22 cases of normal people (normal control group) and who for healthy physical examination were selected in the same period.Then,the correlation between HbA1c level and CSRT were analyzed by the Spearman correlation analysis.· RESULTS:In the high HbA1c group,HbA1c was (10.45±1.30)%,FBG was 10.67±1.64mmol/L and 2hPG was 15.98± 1.38mmol/L,which was higher than that in the low HbA1c group,and there was significant difference between the two groups (P< 0.05).The CSRT in the normal group was lower than the low HbA1c group and the high HbA1c group,and there was significant difference between the groups (P< 0.05).According to the analysis of the Spearman method,there was positive correlation between HbA1c and CSRT,macular volume,average macular thickness,FBG and those parameters,2hPG and them (P<0.01).· CONCLUSION:The HbA1c level is associated with retinal thickening in the macular region of patients with diabetes,which could predict the severity of diabetic retinopathy and provide important guidance for prevention and treatment.

4.
Chinese Critical Care Medicine ; (12): 547-550, 2017.
Article in Chinese | WPRIM | ID: wpr-612794

ABSTRACT

Objective To investigate the effects of high flow hemodialysis (HFHD) on cardiac function in uremia patients. Methods A prospective randomized controlled study was conducted. Sixty patients who were diagnosed with uremia, taken maintenance hemodialysis (MHD) and 30 healthy controls admitted to the Second People's Hospital of Guiyang from December 2014 to June 2015 were enrolled. They were randomly divided into two groups:HFHD group (HFHD three times a week) and the routine hemodialysis group (HD group, HD three times a week), with 30 in each group. Patients in each group were received hemoperfusion and hemofiltration once a month. Before the treatment and 6 months after the treatment, venous blood from all the patients were collected for testing the brain natriuretic peptide (BNP), cardiac troponin T (cTnT) and the ultrasound cardiograph were done at the same period by a special person, the left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), the left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), left ventricular posterior wall thickness (LVPWT), interventricular septum thickness (IVST), early and late diastolic blood flow to the largest ratio (E/A), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) were recorded. Results Compared with the health control group, BNP, cTnT, LVEDD, LVESD, LVESV, LVPWT, IVST were significantly increased, LVEDV were significantly lowered before treatment in the HD group and HFHD group. But no significant differences in the above indexes and E/A, LVEF, LVMI between two groups were found. Compared with the data before treatment, the BNP, LVPWT were significantly lowered after treatment in HD group [BNP (ng/L): 641.50±60.09 vs. 2676.20±454.30, LVPWT (mm): 10.57±1.16 vs. 12.57±1.41, both P < 0.05]. The BNP, LVPWT were significantly lowered in HFHD group as compared with HD group [BNP (ng/L): 253.10±48.77 vs. 641.50±60.09, LVPWT (mm): 9.29±1.08 vs. 10.57±1.16, both P < 0.05]; in addition, the cTnT, IVST, LVMI were significantly lowered after the treatment in HFHD group compared with those before treatment [cTnT (μg/L): 0.014±0.005 vs. 0.028±0.011, IVST (mm): 7.81±1.69 vs. 11.04±2.23, LVMI (g/m2): 149.10±15.77 vs. 158.70±17.25, all P < 0.05], and the LVEF were significantly increased in HFHD group as compared with those before treatment (0.574±0.068 vs. 0.528±0.082, P < 0.05). Conclusion HFHD has obvious advantages than the routine HD in improving cardiac function of uremia patients.

5.
Chinese Critical Care Medicine ; (12): 636-639, 2017.
Article in Chinese | WPRIM | ID: wpr-613389

ABSTRACT

Objective To discuss the effects of multimodal combination dialysis on Klotho protein, fibroblast growth factor-23 (FGF-23) and brain natriuretic peptide (BNP) in patients with maintenance hemodialysis (MHD). Methods A randomized controlled trial (RCT) was conducted. 120 patients who was diagnosed with chronic renal failure (CRF) uremia receiving MHD over 3 months admitted to Blood Purification Centre of Department of Nephrology of the Second People's Hospital of Guiyang from December 2015 to December 2016 were enrolled, who were randomly divided into hemodialysis (HD) group (HD for 8 times a month), HD + hemofiltration (HF) group (HD for 8 times a month + HF once a month), and HD + HF + hemoperfusion (HP) group (HD for 8 times a month + HF for 4 times a month + HP once a month), with 40 patients in each group. Before and after treatment for 6 months and 12 months, blood was taken from venous circuit tube, the serum Klotho protein and FGF-23 levels were determined by enzyme linked immunosorbent assay (ELISA), and the serum BNP level was determined by electrochemiluminescence. Results 120 patients with MHD were enrolled in the final analysis without withdrawal. There were no significant differences in the levels of Klotho protein, FGF-23, or BNP before enrollment among the three groups (all P > 0.05). Compared with those before enrollment, the levels of serum Klotho protein after enrollment in three groups showed a sustained upward tendency, which were higher in HD + HF + HP group than in HD + HF group and HD group (μg/L: 2.59±0.61, 1.63±0.35, 1.13±0.26 at 6 months, F = 119.374, P = 0.000; 6.98±1.21, 3.57±1.03, 2.12±0.43 at 12 months, F = 275.675, P = 0.000); the levels of FGF-23 showed a sustained downward tendency, which were lower in HD + HF + HP group than in HD + HF group and HD group (ng/L: 69.22±38.26, 132.28±61.18, 178.50±74.64 at 6 months, F = 33.509, P = 0.000; 32.81±17.32, 87.93±43.27, 146.33±69.28 at 12 months, F = 55.466, P = 0.000);the BNP showed a similar tendency as FGF-23 (ng/L: 4083.39±2864.53, 7245.69±4643.81, 7969.12±5360.85 at 6 months, F = 8.758, P = 0.000; 1521.86±894.63, 4554.32±1969.84, 5013.89±2033.64 at 12 months, F = 49.003, P = 0.000). Conclusion Multimodal combination dialysis can increase the Klotho protein level, and decrease the levels of FGF-23 and BNP in MHD patients with CRF uremia.

6.
Chinese Traditional Patent Medicine ; (12): 2231-2235, 2017.
Article in Chinese | WPRIM | ID: wpr-668888

ABSTRACT

AIM To explore the effects of ligustrazine on blood rheology,aldose reductase (AR) and renal function in diabetic nephropathy (DN) rats.METHODS The DN rat model was established by intraperitoneal injection of streptozotoein (55 mg/kg),rats were randomly divided into five groups,model group,irbesartan [50 mg/(kg · d)] group,high-,middle-and low-dose of ligustrazine [200,100,50 mg/(kg · d)] groups,together with normal control group.All the rats received daily garage for eight successive weeks.At the end of experiment,blood rheology,blood glucose,aldose reductase in erythrocyte and kidney tissue,24 h urinary protein,blood urea nitrogen,creatinine,creatinine clearance and renal function were observed.RESULTS Compared with the model group,blood rheology,blood glucose and renal function in various treatment groups were effectively improved,and aldose reductase activity was significantly decreased (P < 0.05).HE staining and PAS staining showed that the pathological changes in kidney were significantly alleviated.CONCLUSION Ligustrazine can protect kidney of DN rats by ameliorating blood rheology,decreasing blood glucose and inhibiting aldose reductase activity.

7.
Chinese Journal of Epidemiology ; (12): 543-548, 2009.
Article in Chinese | WPRIM | ID: wpr-261329

ABSTRACT

Objective To study the prevalence and distribution of mental disorders among registered and non-registered residents in Shenzhen. Methods An epidemiological survey on mental disorders were carried out in Shenzhen by stratified multi-stage randomized sampling method; 7134 respondents were assessed through face-to-face interview, using the WHO standardized version on World Mental Health (WMH) Survey Initiative of the Composite International Diagnostic Interview (CIDI3.1). Results (1)The weighting prevalence of mental disorders was 21.87%. The prevalence of non-registered residents was significantly higher than that of the registered residents (22.34% vs. 19.99% ; OR= 1.15,95%CI: 1.03-1.29; P<0.05) and the prevalence of females was significantly higher than that of males (22.68% vs. 19.67%; OR=1.20,95%CI: 1.07-1.34; P<0.05). The weighting prevalence of mood disorders, anxiety disorders and psychoses were 9.62%, 14.45% and 1.40%, respectively. (2) The weighting twelve-month incidence of mental disorders was 13.42%. The incidence of non-registered residents was significantly higher than that of the registered residents (13.80% vs. 11.90%; OR=1.19, 95%CI: 1.03-1.36; P<0.05). (3)The co-morbidity rate between mental disorders was 35.76%. (4)The prevalence and severity of mental disorders were associated with sex, household situation of registration, marital status, education, economic condition and occupation status. Conclusion Mental disorders have become common diseases and serious public health problem in Shenzhen, with non-registered residents and females deserve more attention.

8.
Chinese Journal of Oncology ; (12): 738-740, 2005.
Article in Chinese | WPRIM | ID: wpr-308449

ABSTRACT

<p><b>OBJECTIVE</b>To study the expression and clinical significance of P-gp, GST-pi and Topo II alpha in gastric and colorectal cancers.</p><p><b>METHODS</b>The expression of P-gp, GST-pi and Topo II alpha in 83 cases with gastric or colorectal cancer were examined by immunohistochemistry S-P.</p><p><b>RESULTS</b>The positive expression rates of P-gp, GST-pi, Topo II alpha in normal tissue and gastric and colorectal cancers were 69.9%, 65.1%, 50.6% and 83.1%, 85.5%, 45.8%, respectively. The positive rates of P-gp and GST-pi in gastric and colorectal cancer were significantly higher than those in normal gastric and colorectal tissue (P < 0.05). The expression of Topo II alpha in poorly differentiated cancers was significantly higher than that in well-and moderately differentiated cancers. There was no correlation between other items and clinicopathological parameters (P > 0.05).</p><p><b>CONCLUSION</b>P-gp, GST-pi and Topo II alpha play important role in multidrug resistance. Their mechanisms of drug resistance were different. The detection of expression of P-gp, GST-pi and Topo II alpha has an important guiding significance in chemotherapy for gastric and colorectal cancers.</p>


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1 , Genetics , Adenocarcinoma , Metabolism , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm , Genetics , Colorectal Neoplasms , Metabolism , DNA Topoisomerases, Type II , Genetics , DNA-Binding Proteins , Genetics , Drug Resistance, Neoplasm , Female , Gastrointestinal Neoplasms , Metabolism , Glutathione S-Transferase pi , Genetics , Humans , Immunohistochemistry , Male , Middle Aged , Stomach Neoplasms , Metabolism
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