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1.
Acta Pharmaceutica Sinica ; (12): 3619-3627, 2023.
Article in Chinese | WPRIM | ID: wpr-1004649

ABSTRACT

To investigate the effects and mechanism of the combination of Morus alba L. (Sangzhi) alkaloids(SZ-A) and metformin (Met) on glucose metabolism in type 2 diabetic mice, KKAy mice were divided into four groups according to the glucose and lipid indexes: control group (control), Morus alba L. (Sangzhi) alkaloids group (SZ-A, 100 mg·kg-1), metformin group (Met, 100 mg·kg-1) and combined administration group (combination, Comb, 100 mg·kg-1 SZ-A + 100 mg·kg-1 Met). All groups were administered by gavage once daily for 7 weeks accompanied with monitoring food intake, water intake, body weight as well as glycemia. Additionally, oral glucose tolerance test (OGTT), insulin tolerance test (ITT) and oral sodium pyruvate tolerance test (OPTT) were performed at week 2, week 5, week 6, respectively. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (00004332). We determined the weight and lipid content of liver, and then performed the histopathological analysis after sacrificed. Furthermore, Western blot assay was used to detect the protein levels of key molecules of PI3K/PDK1/Akt/GLUT signaling pathway in liver, muscle and adipose tissue. Compared to the SZ-A or Met monotherapy group, SZ-A + Met significantly improved the glucose metabolism disorder, which was showed in reduced food intake, water intake, the level of fasting blood glucose, postprandial blood glucose and glycosylated hemoglobin A1c (HbA1c) of KKAy mice, as well as improved glucose tolerance, enhanced insulin sensitivity and inhibited gluconeogenesis. In addition, SZ-A + Met obviously up-regulated the protein expression levels in PI3K/PDK1/Akt/GLUT signaling pathway in liver, muscle and adipose tissue of KKAy mice. Moreover, the liver lipid accumulation and blood aminotransferase level of KKAy mice in the combined administration group were significantly reduced. Therefore, we concluded that the combination of SZ-A and Met improved glucose metabolism and inhibited the occurrence and development of T2DM via promoting glucose uptake and utilization, suggesting that the combination of SZ-A and Met is a more useful treatment for T2DM.

2.
Acta Pharmaceutica Sinica ; (12): 1505-1514, 2023.
Article in Chinese | WPRIM | ID: wpr-978711

ABSTRACT

As a member of G protein coupled-receptors superfamily, free fatty acid receptor 1 (FFAR1), is also known as GPR40, has been shown to regulate numerous pathophysiological processes in a variety of tissues and organs. The activated FFAR1 has a variety of biological functions. For instance, it can not only regulate metabolism of fatty acids and glucose, but also play an important role in immune inflammatory response, it may be a potential drug target for the treatment of various chronic inflammatory diseases. In this review, we focus on the recent researches of FFAR1's action in the regulation of pathophysiological processes, its molecular mechanism and new agonists development. At the same time, this review will take the discovery of series FFAR1 agonists as examples, and display the applied prospects of FFAR1.

3.
Acta Pharmaceutica Sinica ; (12): 386-395, 2023.
Article in Chinese | WPRIM | ID: wpr-965708

ABSTRACT

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the serum in STZ rats, and inhibited the gene expression of these inflammatory factors in the sciatic nerve. In summary, metformin significantly increased nerve conduction velocity, improved sciatic nerve morphological abnormalities and pain in DPN rats, which may be related to its effect in improving oxidative stress and reducing inflammation.

4.
Biomedical and Environmental Sciences ; (12): 45-57, 2022.
Article in English | WPRIM | ID: wpr-927631

ABSTRACT

OBJECTIVE@#This study aimed to assess the associations between maternal drug use, cytochrome P450 ( CYP450) genetic polymorphisms, and their interactions with the risk of congenital heart defects (CHDs) in offspring.@*METHODS@#A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020.@*RESULTS@#After adjusting for potential confounding factors, the results show that mothers who used ovulatory drugs (adjusted odds ratio [a OR] = 2.12; 95% confidence interval [ CI]: 1.08-4.16), antidepressants (a OR = 2.56; 95% CI: 1.36-4.82), antiabortifacients (a OR = 1.55; 95% CI: 1.00-2.40), or traditional Chinese drugs (a OR = 1.97; 95% CI: 1.26-3.09) during pregnancy were at a significantly higher risk of CHDs in offspring. Maternal CYP450 genetic polymorphisms at rs1065852 (A/T vs. A/A: OR = 1.53, 95% CI: 1.10-2.14; T/T vs. A/A: OR = 1.57, 95% CI: 1.07-2.31) and rs16947 (G/G vs. C/C: OR = 3.41, 95% CI: 1.82-6.39) were also significantly associated with the risk of CHDs in offspring. Additionally, significant interactions were observed between the CYP450genetic variants and drug use on the development of CHDs.@*CONCLUSIONS@#In those of Chinese descent, ovulatory drugs, antidepressants, antiabortifacients, and traditional Chinese medicines may be associated with the risk of CHDs in offspring. Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development.


Subject(s)
Adult , Female , Humans , Infant, Newborn , Pregnancy , Cytochrome P-450 Enzyme System/genetics , Genotype , Heart Defects, Congenital/genetics , Polymorphism, Genetic , Pregnancy Complications/drug therapy
5.
Journal of Experimental Hematology ; (6): 12-17, 2022.
Article in Chinese | WPRIM | ID: wpr-928663

ABSTRACT

OBJECTIVE@#To analyze the efficacy of children with B-cell acute lymphoblastic leukemia (B-ALL) without prognostic fusion genes treated by CCLG-ALL 2008, and investigate the related factors affecting the recurrence of the patients.@*METHODS@#B-ALL patients without prognostic fusion genes treated by the protocol of CCLG-ALL 2008 in our hospital from March 2008 to December 2012 were retrospectively analyzed. Follow-up time was ended in August 31, 2019. The median follow-up time was 92 months (range 0-136 months). Kaplan-Meier was used to detect the RFS, and COX multivariate regression analysis was employed to identify the independent factors affecting the recurrence of the patients.@*RESULTS@#There were 140 males and 99 females enrolled in this study. The ratio of male to female was 1.41∶1. The median age was 4.4 years old and the median number of WBC at initial stage was 4.98×109/L. There were 77 cases relapsed during the observation while 162 without relapsed, 16 cases lost to follow-up and 72 cases died. The recurrence and mortality rate was 32.22% and 30.1%, respectively, in which 45 cases died of recurrence (62.5% of the total deaths). Univariate analysis showed that the age≥6 years old, WBC >100×109/L, the bone marrow blasts on day 15≥25%, the bone marrow minimal residual disease (MRD) at week 12 >10-4, and the higher risk were the main factors affecting the recurrence of the patients (P<0.05). Multivariate COX regression analysis showed that age≥6 years old, WBC >100×109/L, bone marrow MRD >10-4 at the 12th week were the independent risk factors affecting recurrence of the patients.@*CONCLUSION@#Age, initial WBC, and bone marrow MRD at the 12th week were correlated with recurrence in children with B-ALL without prognostic fusion genes, which can be used as prognostic indices of recurrence risk in clinical.


Subject(s)
Child , Child, Preschool , Female , Humans , Male , Antineoplastic Combined Chemotherapy Protocols , Disease-Free Survival , Neoplasm, Residual , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Prognosis , Recurrence , Retrospective Studies
6.
Acta Pharmaceutica Sinica ; (12): 352-359, 2021.
Article in Chinese | WPRIM | ID: wpr-873759

ABSTRACT

Thiazolidinediones (TZDs) are currently the only recognized insulin sensitizers available for the clinical treatment of type 2 diabetes. Although their advantages are recognized, the profiles of numerous adverse effects hinder the continued use of these drugs. Peroxisome proliferator-activated receptor γ (PPARγ) is known as a receptor for TZDs, and its underlying mechanisms of pharmacological actions and adverse effects have been deeply explored. To maximally preserve the PPARγ-mediated insulin sensitizing effects and reduce the occurrence of related adverse effects, the concept of "selective PPARγ modulators (SPPARMs)" has been proposed and developed, guiding the development of new drugs. In this review, we summarize the recent research progress in the definition of SPPARMs, the candidate classification and the molecular underpinnings, as well as present the discovery of the YR series compounds as an example, and discuss the potential application prospects of SPPARMs.

7.
Chinese Journal of Contemporary Pediatrics ; (12): 547-554, 2021.
Article in Chinese | WPRIM | ID: wpr-879892

ABSTRACT

OBJECTIVE@#To study the association between maternal reduced folate carrier (@*METHODS@#A hospital-based case-control study was conducted. The mothers of 683 infants with CHD who attended the Department of Cardiothoracic Surgery, Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group. The mothers of 740 healthy infants without any deformity who attended the hospital during the same period of time were enrolled as the control group. A questionnaire survey was performed to collect the exposure data of subjects. Venous blood samples of 5 mL were collected from the mothers for genetic polymorphism detection. A multivariate logistic regression analysis was used to evaluate the association of @*RESULTS@#After control for confounding factors, the multivariate logistic regression analysis showed that maternal @*CONCLUSIONS@#Maternal


Subject(s)
Child , Female , Humans , Infant , Case-Control Studies , Genetic Predisposition to Disease , Genotype , Heart Defects, Congenital/genetics , Polymorphism, Single Nucleotide , Reduced Folate Carrier Protein/genetics , Risk Factors
8.
Korean Journal of Radiology ; : 1331-1338, 2020.
Article in English | WPRIM | ID: wpr-894682

ABSTRACT

Objective@#To evaluate urologist satisfaction on structured prostate MRI reports, including report with tumor-node-metastasis (TNM) staging (report B) and with Prostate Imaging Reporting and Data System (PI-RADS) score with/without TNM staging (report C, report with PI-RADS score only [report C-a] and report with PI-RADS score and TNM staging [C-b]) compared with conventional free-text report (report A). @*Materials and Methods@#This was a prospective comparative study. Altogether, 3015 prostate MRI reports including reports A, B, C-a, and C-b were rated by 13 urologists using a 5-point Likert Scale. A questionnaire was used to assess urologist satisfaction based on the following parameters: correctness, practicality, and urologist subjectivity. Kruskal-Wallis H-test followed by Nemenyi test was used to compare urologists’ satisfaction parameters for each report type. The rate of urologist-radiologist recalls for each report type was calculated. @*Results@#Reports B and C including its subtypes had higher ratings of satisfaction than report A for overall satisfaction degree, and parameters of correctness, practicality, and subjectivity (p 0.05). Compared with report C-b (p > 0.05), report B and C-a (p 0.05). No statistical difference was found between report C-a and C-b in overall satisfaction degree and all three parameters (p > 0.05). The rate of urologist-radiologist recalls for reports A, B, C-a and C-b were 29.1%, 10.8%, 18.1% and 11.2%, respectively. @*Conclusion@#Structured reports, either using TNM or PI-RADS are highly preferred over conventional free-text reports and lead to fewer report-related post-hoc inquiries from urologists.

9.
Korean Journal of Radiology ; : 1331-1338, 2020.
Article in English | WPRIM | ID: wpr-902386

ABSTRACT

Objective@#To evaluate urologist satisfaction on structured prostate MRI reports, including report with tumor-node-metastasis (TNM) staging (report B) and with Prostate Imaging Reporting and Data System (PI-RADS) score with/without TNM staging (report C, report with PI-RADS score only [report C-a] and report with PI-RADS score and TNM staging [C-b]) compared with conventional free-text report (report A). @*Materials and Methods@#This was a prospective comparative study. Altogether, 3015 prostate MRI reports including reports A, B, C-a, and C-b were rated by 13 urologists using a 5-point Likert Scale. A questionnaire was used to assess urologist satisfaction based on the following parameters: correctness, practicality, and urologist subjectivity. Kruskal-Wallis H-test followed by Nemenyi test was used to compare urologists’ satisfaction parameters for each report type. The rate of urologist-radiologist recalls for each report type was calculated. @*Results@#Reports B and C including its subtypes had higher ratings of satisfaction than report A for overall satisfaction degree, and parameters of correctness, practicality, and subjectivity (p 0.05). Compared with report C-b (p > 0.05), report B and C-a (p 0.05). No statistical difference was found between report C-a and C-b in overall satisfaction degree and all three parameters (p > 0.05). The rate of urologist-radiologist recalls for reports A, B, C-a and C-b were 29.1%, 10.8%, 18.1% and 11.2%, respectively. @*Conclusion@#Structured reports, either using TNM or PI-RADS are highly preferred over conventional free-text reports and lead to fewer report-related post-hoc inquiries from urologists.

10.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 827-836, 2020.
Article in English | WPRIM | ID: wpr-881025

ABSTRACT

Jin-tang-ning (JTN), a Chinese patent medicine, mainly comprised of Bombyx moriL., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes (T2DM). Recently, we have reported that JTN could ameliorate postprandial hyperglycemia and improved β cell function in monosodium glutamate (MSG)-induced obese mice, suggesting that JTN might play a potential role in preventing the conversion of impaired glucose tolerance (IGT) to T2DM. In this study, we evaluated the effect of JTN on the progression of T2DM in the pre-diabetic KKAy mice. During the 10 weeks of treatment, blood biochemical analysis and oral glucose tolerance tests were performed to evaluate glucose and lipid profiles. The β cell function was quantified using hyperglycemic clamp at the end of the study. JTN-treated groups exhibited slowly raised fasting and postprandial blood glucose levels, and also ameliorated lipid profile. JTN improved glucose intolerance after 8 weeks of treatment. Meanwhile, JTN restored glucose-stimulated first-phase of insulin secretion and induced higher maximum insulin levels in the hyperglycemic clamp. Thus, to investigate the underlying mechanisms of JTN in protecting β cell function, the morphologic changes of the pancreatic islets were observed by optical microscope and immunofluorescence of hormones (insulin and glucagon). Pancreatic protein expression levels of key factors involving in insulin secretion-related pathway and ER stress were also detected by Western blot. Pre-diabetic KKAy mice exhibited a compensatory augment in β cell mass and abnormal α cell distribution. Long-term treatment of JTN recovered islet morphology accompanied by reducing α cell area in KKAy mice. JTN upregulated expression levels of glucokinase (GCK), pyruvate carboxylase (PCB) and pancreas duodenum homeobox-1 (PDX-1), while down-regulating C/EBP homologous protein (Chop) expression in pancreas of the hyperglycemic clamp, which indicated the improvement of mitochondrial metabolism and relief of endoplasmic reticulum (ER) stress of β cells after JTN treatment. These results will provide a new insight into exploring a novel strategy of JTN for protecting β cell function and preventing the onset of pre-diabetes to T2DM.

11.
Acta Pharmaceutica Sinica ; (12): 1225-1233, 2019.
Article in Chinese | WPRIM | ID: wpr-780225

ABSTRACT

Sangzhi alkaloids (SZ-A) are derived from traditional Chinese medicine Ramulus Mori, serving well as an innovative antidiabetic drug, due to α-glucosidase inhibition. To evaluate the potency of glucosidase inhibitory effect of SZ-A, the enzyme-based screening platforms, including sucrase, maltase and amylase were established, and IC50 was calculated. The effects of SZ-A on postprandial blood glucose at a single dose, oral sucrose, starch and glucose loading were determined in normal ICR mice and alloxan-induced hyperglycemic mice. To confirm the anti-diabetic effects of SZ-A on glucose and lipid metabolism after long-term administration, the postprandial and fasting blood glucose, serum insulin, urinary glucose levels, glycosylated serum proteins and blood lipid levels were determined in high-fat fed C57 obese mice (pre-diabetic HFC57 mice) and diabetic rats induced by streptozotocin (STZ). The Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College approved all of the protocols for this research. We found that SZ-A exhibited a significant inhibitory effect on the sucrase and maltase. SZ-A showed no effect on amylase. In normal ICR mice and alloxan-induced hyperglycemic mice, SZ-A at a single dose significantly delayed and reduced the peak of blood glucose after sucrose or starch loading, but showed no effect on the increase of blood glucose after glucose loading. In STZ diabetic rats, SZ-A significantly reduced the postprandial or fasting blood glucose levels, glycosylated serum proteins and urinary glucose. SZ-A also reduced serum triglyceride (TG) and cholesterol (TC) levels after 3 weeks of treatment. SZ-A ameliorated the postprandial blood glucose or the fasting blood glucose elevation, and reduced the incidence of hyperglycemia in HFC57 mice. SZ-A decreased the basal insulin level, improved insulin sensitivity, and ameliorated glucose intolerance in pre-diabetic HFC57 mice. Our results indicated that SZ-A had a novel inhibitory activity on α-glucosidase, especially on disaccharidases. SZ-A at a single dose significantly reduced the peak of blood glucose elevation and delayed the increase of blood glucose in normal and diabetic mice after disaccharide and polysaccharide loading. Long-term SZ-A treatment improved glucose and lipid metabolic profiles by delaying carbohydrate absorption from the intestine and reduced the postprandial blood glucose levels in both pre-diabetic and diabetic animal models. Therefore, SZ-A application may display a beneficial role in preventing the development and complications of diabetes.

12.
Journal of Practical Radiology ; (12): 988-991, 2019.
Article in Chinese | WPRIM | ID: wpr-752482

ABSTRACT

Objective To investigate the methods of screening specific aptamers for (EpCAM)Gpositive prostate cancer (PCa)cells by cellGSELEX technique.Methods A random DNA library was designed to screen EpCAMGspecific DNA aptamers from human prostate cancer cells expressing EpCAM molecule by cellGSELEX technique.After 12 rounds of in vitro screening,DNA products were cloned and sequenced.Flow cytometry and cellular immunofluorescence were used to detect the specific binding ability of aptamers to target cells.Results Two aptamers of Ep1 and Ep2 were selected.Both of them could specifically bind to EpCAMGpositive cancer cells LNCap,PCG3 ,DU1 45 , and HEK293T cells transfected with target molecule.The binding rates of Ep1 were 61.0%,74.3%,5 9.1% and 60.3%.The binding rates of Ep2 were 65.1%,77.8%,54.2% and 58.3%.Neither of them could bind to HEK293T cells transfected with empty vector with the binding rate of 5.4% in Ep1 and 3.3% in Ep2,respectively.Flow cytometry analysis and confocal images indicated that the EpCAM aptamers could specifically recognize human PCa cells expressing EpCAM,but could not bind to EpCAMGnegative cells.Conclusion EpCAM aptamers derived from cellGSELEX technology can recognize and bind to EpCAMGpositive PCa cells specifically,which may provide new ideas for the specific diagnosis and targeted therapy of prostate cancer,and lay an experimental basis for the other specific diagnosis and treatment schemes of malignant tumors.

13.
Journal of Experimental Hematology ; (6): 1033-1037, 2018.
Article in Chinese | WPRIM | ID: wpr-689533

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the therapeutic safety and efficacy of VDMP re-induction regimen in Chinese children with relapsed acute lymphoblastic leukemia (ALL).</p><p><b>METHODS</b>Forty-one patients with relapsed ALL were prospectively enrolled in this study. All the patients were distributed in 3 children's hospitals and treated with VDMP regimen as the first re-induction chemotherapy. Therapeutic efficacy and side-effects were analyzed.</p><p><b>RESULTS</b>The ratio of male to female was 27:14. The median age was 7.9 (2.2-15.4) years old. Patients relapsed at very early, early, and late stage were 7 cases, 11 cases, and 23 cases, respectively.The immunophenotype analysis showed that 38 cases were B-ALL, and 3 cases were T-ALL. All patients suffered from grade 4 of neutropenia and forty(97.6%) cases got infection, of them one case died. Thirty-nine(95.1%) cases had nonhematologic adverse event at least one organ involved grade 3 in 38 out of 41 cases, the VDMP therapy was completed, 34(89.5%) cases achieved a complete remission (CR), 1 case achieved partial remission(PR), and 3 cases didn't get remission. Follow-up data of 38 cases with completing VDMP chemotherapy were obtained, only one case was lost. Among 37 cases available for evaluation, 16 cases received allo-hematopoietic stem cell transplantation(allo-HSCT) after chemotherapy, and 13 patients survived, while 21 cases did not receive allo-HSCT(treated with chemotherapy only), and 8 patients survived.The overall survival rate of allo-HSCT group was significantly higher than that of those treated with chemotherapy only(P<0.05).</p><p><b>CONCLUSION</b>VDMP re-induction regimen is effective and well tolerable for pafients in the treated children with relapsed ALL. After remission, allo-HSCT is recommended with the aim of long survival.</p>


Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Male , Antineoplastic Combined Chemotherapy Protocols , Hematopoietic Stem Cell Transplantation , Induction Chemotherapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Remission Induction , Treatment Outcome
14.
Chinese Medical Equipment Journal ; (6): 61-64, 2018.
Article in Chinese | WPRIM | ID: wpr-699993

ABSTRACT

Objective To investigate the feasibility of combined CT angiography(CTA)of head,neck and aorta in acute type A aortic dissection (ATAAD) and whether the incremental craniocervical information benefits the surgeon and leads to improved clinical outcomes.Methods One hundred and twenty ATAAD patients in a CAC group underwent combined aortic CTA and 123 ATAAD patients in a control group underwent conventional aortic CTA.In the CAC group,the image quality was analyzed and critical CTA findings in craniocervical arteries were determined for further surgery procedure.The radiation dose,intraoperative cerebral protection method,and postoperative intensive care units(ICU)time,in-hospital time,neurologic dysfunction(ND)and all-cause mortality were compared between the two groups.Results The CAC group had all the carotid and cerebral arteries diagnosed successfully. There were 13 patients replaced conventional unilateral antegrade selective cerebral perfusion with bilateral one according to the head and neck CTA images in the CAC group. The CAC group had effective radiation dose,postoperative ND,ICU time and in-hospital time significantly lower than those of the control group (P<0.05).There were no statistical differences between the all-cause morbidities of the two groups (P>0.05).Conclusion A combined CTA of head, neck and aorta in ATAAD is feasible. The incremental craniocervical information may lead to improved clinical outcomes.

15.
Journal of Practical Radiology ; (12): 537-541, 2017.
Article in Chinese | WPRIM | ID: wpr-513778

ABSTRACT

Objective To probe the value of 3.0T MRI in the preoperative assessment of rectal carcinoma.Methods The study recruited 41 patients who were confirmed by biopsy of rectal carcinoma and underwent conventional MRI, high-resolution MRI and diffusion weighted imaging(DWI), the distance from the inferior part of tumor to transitional skin and the percentage of circumferential invasion were measured, the tumor's T staging, N staging,and the status of circumferential resection margin(CRM) and extramural vascular invasion(EMVI) were assessed.MRI findings were compared with endoscope and postoperative pathological results.Results MRI could accurately show the distance from the inferior part of tumor to transitional skin(P>0.05);The mean percentage of circumferential invasion for the tumor with T1-T2 and T3 were 61%,83% respectively (P>0.05);The total accuracy of T,N staging diagnose were 80.5%,75.6% respectively, which had a better consistent with pathological T,N staging(Kappa=0.564,0.634);The total accuracy of CRM and EMVI diagnose were 90.2%,73.2% respectively,which had a better or moderate consistent with pathological diagnose(Kappa=0.765,0.461).Conclusion 3.0T MRI has the unique application in the preoperative assessment of rectal carcinoma, which can provide more comprehensive information for clinic.

16.
Acta Pharmaceutica Sinica ; (12): 1424-1431, 2017.
Article in Chinese | WPRIM | ID: wpr-779744

ABSTRACT

Recent studies indicate that insulin-sensitizing activity of TZDs occurs through the inhibition of PPARγ Ser273 phosphorylation mediated by cyclin-dependent kinase 5(Cdk5), which is resulted from the binding activity for PPARγ. While, the side effects of TZDs may be related to the agonistic potency for PPARγ. In this article, 15 target compounds were designed and synthesized based on the structure of PPAR γ partial agonist INT131, with the aim of maintaining the insulin-sensitizing activity and reducing the side effects of INT131. The structures of these compounds were confirmed by 1H NMR and ESI-MS, and their binding activities and agonistic potencies for PPARγ were measured. The binding activity of compound 15 is 88.47% of rosiglitazone, which is similar to INT131 (98.55%), but the agonistic potency of compound 15 is 1.41% of rosiglitazone, obviously lower than INT131 (15.18%).

17.
Acta Pharmaceutica Sinica B ; (6): 461-469, 2017.
Article in English | WPRIM | ID: wpr-256734

ABSTRACT

Refined-JQ (JQ-R) is a mixture of refined extracts from(Ranunculaceae),(Leguminosae) and(Caprifoliaceae), the three major herbs of JinQi-JiangTang tablet, a traditional Chinese medicine (TCM) formula. The mechanisms by which JQ-R regulates glucose metabolism and improves insulin sensitivity were studied in type 2 diabetic KKmice and insulin-resistant L6 myotubes. To investigate the mechanisms by which JQ-R improves insulin sensitivity, a model of insulin-resistant cells induced with palmitic acid (PA) was established in L6 myotubes. Glucose uptake and expression of factors involved in insulin signaling, stress, and inflammatory pathways were detected by immunoblotting. JQ-R showed beneficial effects on glucose homeostasis and insulin resistance in a euglycemic clamp experiment and decreased fasting insulin levels in diabetic KKmice. JQ-R also improved the plasma lipid profiles. JQ-R directly increased the activity of superoxide dismutase (SOD) and decreased malondialdehyde (MDA) as well as inducible nitric oxide synthase (iNOS) levels in insulin-resistant L6 cells, and elevated the insulin-stimulated glucose uptake with upregulated phosphorylation of AKT. The phosphorylation levels of nuclear factor kappa B (NF-B p65), inhibitor of NF-B (IB), c-Jun N-terminal kinase (JNK1/2) and extracellular-signal-regulated kinases (ERK1/2) were also changed after JQ-R treatment compared with the control group. Together these findings suggest that JQ-R improved glucose and lipid metabolism in diabetic KKmice. JQ-R directly enhanced insulin-stimulated glucose uptake in insulin-resistant myotubes with improved insulin signalling and inflammatory response and oxidative stress. JQ-R could be a candidate to achieve improved glucose metabolism and insulin sensitivity in type 2 diabetes mellitus.

18.
Journal of Experimental Hematology ; (6): 365-370, 2017.
Article in Chinese | WPRIM | ID: wpr-311537

ABSTRACT

<p><b>OBJECTIVE</b>To explore the clinical features and prognostic factors of pediatric acute lymphoblastic leukemia (ALL) in high-risk (HR) group.</p><p><b>METHODS</b>A total of 421 children with ALL in the Children's Hospital of Soochow University from August 2008 to March 2013 were diagnosed and treated according to the Chinese Children Leukemia Group (CCLG)-2008 Protocol. Among different risk-groups, 148 cases were stratified into the low-risk group and 191 cases were included in the moderate-risk group. Eight-two patients of the high-risk group were analyzed retrospectively for their clinical features, 5-year event-free survival (EFS) rate and overall survival (OS) rate.</p><p><b>RESULTS</b>The median follow-up times of 82 patients were 64 months(3.0-76.3 months), 55 patient achieved complete remission(CR) after 1 cycle of induction chemotherapy(CR rate 67.1%), 25 patients relapsed(30.5%) mainly in very early and early relapse phases, significantly different from the low-risk group (P=0.013), 27 pateitns died(32.9%). The 5-year pEFS and pOS were 57.20% and 58.5%, respectively. Phor BCR/ABLand MRD>10on the 33rd day in the high-risk group were 2 main factors influencing EFS and OS according to single factor analysis. Phor BCR/ABLwas an independent prognostic factor, however, the MRD value on the 33rd day was not statistically significant differente by virtue of COX regression analysis.</p><p><b>CONCLUSION</b>The clinical feature of children with ALL in high risk group display low induction CR rate, high recurrence rate and the lower 5-year pEFS. Phor BCR/ABLis regarded as an independent factor of poor prognosis.</p>

19.
International Eye Science ; (12): 2130-2133, 2017.
Article in Chinese | WPRIM | ID: wpr-669243

ABSTRACT

AIM:To compare the clinical outcome of anterior chamber intraocular lens (IOL) at Ⅰ stage versus sclerafixed IOL at Ⅱ stage in complicated cataract surgeries with inadequate capsular support.METHODS:Complicated cataract surgeries with anterior chamber IOL (ACIOL) or scleral-fixated IOL implantation from January 2003 to December 2014 when capsular support was inadequate were included and analyzed.Postoperative best-corrected visual acuity (BCVA) were compared.Postoperative complications were recorded and analyzed.RESULTS:Totally 84 eyes and 79 eyes were included in the ACIOL group and in the scleral-fixated IOL group,respectively.The mean postoperative logarithm of minimal angle of resolution (LogMAR) BCVA at 1a was 0.30±0.64 and 0.33±0.34 in the ACIOL group and the scleral-fixated IOL group,respectively (t=0.407,P=0.712).The mean latest LogMAR BCVA was 0.67±0.55 and 0.62 ± 0.50 in the primary ACIOL group and the secondary scleral-fixated IOL group,respectively (t=0.225,P=0.545).There were more early postoperative complications in the ACIOL group (x2 =14.613.P<0.001).No difference in late postoperative complications was found between the two groups (x2 =0.231,P=0.267).Regression analysis suggested that ACIOL and scleralfixated IOL implantation had similar latest postoperative LogMAR BCVA (t=0.397,P=0.957);however the existence of late complications were related with a worse final visual outcome (t=22.156,P<0.001).CONCLUSION:The long-term differences in the visual outcomes and complication profiles after ACIOL at Ⅰ stage or scleral-fixated IOL implantation at Ⅱ stage in a complicated cataract operation are not found when capsular support is inadequate.

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Chinese Journal of Medical Imaging ; (12): 658-661, 2017.
Article in Chinese | WPRIM | ID: wpr-706381

ABSTRACT

Purpose To explore the application of intra voxel incoherent motion diffusionweighted imaging (IVIM-DWI) quantitative parameters in evaluating the pathological stage of pancreatic cancer by comparing the manifestations of IVIM-DWI in patients with pancreatic cancer in different differentiaed degrees as there lacked effective screening instrument for the early diagnosis of pancreatic cancer.Materials and Methods Sixteen patients with pathologically proved pancreatic cancer (10 with high-moderation differentiation while 6 with low differentiation) were enrolled,and 3.0T MRI was used to conduct pancreatic DWI with multiple b values.IVIM double-exponential model was used to analyze the measurement parameters of DWI with multiple b values,so as to measure the slow apparent diffusion coefficient (ADCslow),fast apparent diffusion coefficient (ADCfast) and filling fraction (f).Results The ADCslow value was evidently lower in patients with high-moderate differentiated pancreatic cancer than those with low differentiated pancreatic cancer [(0.546± 0.041)× 10-3 mm2/s vs.(0.677± 0.120)× 10-3 mm2/s,P<0.05],and f value was notably higher in patients with high-moderate differentiated pancreatic cancer than those with low differentiated pancreatic cancer [(59.3 ± 8.8)% vs.(41.7±22.4)%,P<0.05].The area under the curve of ADCslow was higher than that of f when distinguishing high-moderate differentiated and low differentiated pancreatic cancer (0.850>0.750).The sensitivity and specificity were 100.00% and 83.33% when ADCslow ≤ 0.599×10-3 mm2/s,and were 100.00% and 66.67% when f>44.7% in distinguishing high-moderate differentiated and low differentiated pancreatic cancer,respectively.Conclusion ADCslow and f,as the quantitative parameters for IVIM-DWI,can distinguish high-moderate differentiated and low differentiated pancreatic cancer,and predict the pathological stage of pancreatic cancer before operation.Moreover,they also have high diagnostic efficacy in distinguishing high-moderate differentiated and low differentiated pancreatic cancer.

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