1.Molecular targeted therapy of triple-negative breast cancer
Journal of International Oncology 2014;(9):662-665
Treatment options are limited for triple negative breast cancer (TNBC)since endocrinother-apy and targeted therapy that aims directly at human epidermal growth factor receptor-2 (HER-2)are ineffec-tive.As such,in addition to surgical treatment,the mainstay of treatment of TNBC is systemic cytotoxic chemo-therapy.The targeted therapy of TNBC is becoming a research hotspot because of traditional chemotherapy cura-tive effect is not good enough.A large number of clinical trials have found that patients with TNBC can get ben-efits from targeted molecular strategies including poly-adenosine diphosphate glucose pyrophospheralase-ribose polymerase-1 (PARP-1 )inhibitor and epidermal growth factor receptor (EGFR)inhibitor.
2.Genetic abnormalities and their relationship with the clinical features in pediatric Burkitt lymphoma
Miao WANG ; Liya SU ; Wenping YANG ; Beibei LYU ; Liping GONG
Journal of Leukemia & Lymphoma 2013;22(4):197-201
Objective To analyze the molecular cytogenetic abnormalities and pathogenesis of pediatric Burkitt lymphoma (BL) by array comparative genomic hybridization (aCGH).Methods First,immunophenotype,molecular genetics and EB virus (EBV) infection status were detected using immunohistochemistry and fluorescence in situ hybridization in 21 pediatric BL patients.Second,in addition to detecting genome-wide genetic gain/deletion status,aCGH results with EBV infection status were also correlated.Results aCGH results showed genetic alterations in 19 cases (90.5 %).Generally,frequency of chromosomal gain was higher than chromosomal deletion.The regions of frequently-occurring small DNA genomic fragment gains (≥40 % cases) were 3q21.1,5p13.2,19q13.32,12q23.1,14q32.33,6q27,20p13 and 20p11.21.Large DNA fragment gains and deletions could be detected in 42.9 % (9/21) cases in the 14q24.2 and 14q32.33 regions.There was no significant difference in genetic alterations between EBV (+) and EBV (-) BL cases (P≥0.05).Conclusion aCGH results show that BL cases have complex genetic alterations,which have no significant difference between EBV(+) and EBV(-) cases.Most BL cases show large DNA segment deletion or acquisition of 14q,indicating that 14q gene alteration plays an important role in the pathogenesis of BL.
3.Cost-minimization Analysis of Four Kinds of Premixed Insulin in the Therapy for Newly Diagnosed Type 2 Diabetes
Guofei REN ; Liya GONG ; Jiaping SUN ; Lingdi ZHANG
China Pharmacist 2017;20(3):503-505
Objective:To evaluate the short-term economic effects of four kinds of premixed insulin in newly diagnosed type 2 dia-betes mellitus. Methods:A total of 120 newly diagnosed patients with type 2 diabetes mellitus were divided into four groups according to the kind of premixed insulin, group A was treated with insulin aspart 30 injection, group B was treated with insulin lispro 25 injec-tion, group C was treated with isophane protamine biosynthetic human insulin injection and group D was treated with protamine zinc re-combinant human insulin injection. The course of treatment was three months. The therapy efficacy was assessed by the remission rate in three months. The short-term economic effect was evaluated by the cost-minimization analysis method. Results:The remission rate of group A, B, C and D respectively was 48. 39%, 48. 28%, 51. 61% and 51. 72% without significant difference (P>0. 05). The average cost per person of the four groups was 1195. 52, 1202. 41, 1220. 69 and 1258. 84 yuan, and the average medicine cost per person was 750. 52, 689. 41, 754. 69 and 764. 34 yuan, respectively. There was no significant difference in cost among the four groups (P >0. 05). Conclusion:All the four kinds of premixed insulin can be used for the starting treatment with the similar total cost, and in relative terms, aspart 30 injection and insulin lispro 25 injection are better for the initial treatment of diabetes.
4.Recombinant human glucagon-like peptide-1 (7-36) enhances insulin release and insulin mRNA expression in INS-1 cells
Qiuhong GONG ; Jinning LOU ; Liya YE ; Guangwei LI
Chinese Journal of Endocrinology and Metabolism 2000;0(06):-
In INS-1 cells, the insulin secretion was investigated by radioimmunoassay (RIA) after 4 h incubation in medium containing different concentrations of glucose and recombinant human glucagon-like peptide-1 (rhGLP-1) (7-36). Insulin mRNA level in INS-1 cells was assessed by a semi-quantitative RT-PCR method. rhGLP-1 (7-36) is not only a powerful insulin secretagogue, but also can increase insulin gene expression in INS-1 cells.
5.Ketoacidosis in newly-onset type 1 diabetes mellitus in children and adolescents from 2010 to 2012
Liya WEI ; Chunxiu GONG ; Di WU ; Yi WANG ; Fengting LI ; Rui WANG
Chinese Journal of Endocrinology and Metabolism 2015;(9):752-757
Objective To investigate the incidence of newly-onset type 1 diabetes mellitus ( T1DM ) complicated with ketoacidosis(DKA) and its relevant factors in pediatrics. Methods Hospital records of 317 T1DM children below 18 years of age, diagnosed from 2010 to 2012 were reviewed. By using retrospectively analyzed data of inpatients with newly-diagnosed T1DM, the incidence of DKA was calculated. In this study, the influential factors of DKA included gender, age, residence, family history of diabetes mellitus, duration of symptoms, misdiagnosis or missed diagnosis, and delayed treatment. Patients were divided into two groups:group 1, aged<5 year and group 2, aged>5 year. Results Of all patients diagnosed with T1DM, 175 ( 55. 2%) presented with DKA, and mild, moderate, and severe DKA accounted for 26. 5%, 23. 9%, 49. 6%, respectively. The incidences of DKA in group 1 andgroup2were67.5% and48.0% (P=0.001),withthehighestfrequency(70.3%)inpatientsaged<2 years. The proportion of severe DKA in group 1 was significantly higher than that of group 2 (60. 0% vs 41. 3%, P=0. 048). The rates of misdiagnosis and missed diagnosis in the two groups were respectively 27. 4% and 12. 0%(P=0. 001), being 37. 8% in children<2 years. The HbA1C level of group 1 was lower than group 2 (11. 50% vs 12.54%,P=0.001). Intheacutemetabolicandhoneymoonperiod,Cpeptidelevelsofgroup1werebothlowerthan those of group 2 [(0. 36 vs 0. 55) ng/ml, P=0. 001;(0. 40 vs 0. 61) ng/ml, P=0. 02]. The DKA incidence of patients with misdiagnosis or missed diagnosis was significantly increased(83. 9% vs 49. 0%, P=0. 000). Compared with those without DKA, C peptide level of patients with DKA was lower in the acute metabolic period[(0. 56 vs 0.40)ng/ml,P<0. 01], but no difference in honeymoon period[(0. 67 vs 0. 59)ng/ml,P=0. 22]. Logistic regression showed that age, misdiagnosis or missed diagnosis were associated with the presence of DKA. The possibility of the occurrence of DKA in patients aged>5 years was half of patients aged<5 years ( OR=0. 448, P=0. 003), and the risk of DKA in patients with misdiagnosis or missed diagnosis was higher (OR=5. 640, P=0. 005). Conclusion DKA in patients with newly-onset T1DM is frequent and often severe. Multivariate analysis revealed that patients aged <5 years and those with misdiagnosis or missed diagnosis are encountered high risk of DKA.
6.Effect of hyperbaric oxygen therapy on serum PCT, WBC and hs-CRP levels in children with acute necrotizing fasciitis and its efficacy
Huizhong NIU ; Liya WANG ; Yanqing DONG ; Feng LIU ; Pengju ZHANG ; Yingxin GONG
Chinese Journal of Biochemical Pharmaceutics 2015;35(10):32-34
Objective To investigate the effect of hyperbaric oxygen therapy on serum procalcitonin (PCT), white blood cells(WBC) and high-sensitivity C-reactive protein (hs-CRP) levels in children with necrotising fasciitis (NF) and its efficacy, and explore the diagnosis value of above indicators.Methods From March 2011 to June 2014,50 cases children with acute necrotic fasciitis treated in Children's Hospital of Hebei Province as study group,which were randomly divided into hyperbaric oxygen group (n =25) and routine group (n =25) .The routine group received the routine therapy of incision and drainage to clear the lesion, hyperbaric oxygen group received hyperbaric oxygen therapy on the basis of routine group,while 50 healthy children were selected as control group.The serum PCT, WBC, hs-CRP levels, efficacy, complications, death and hospitalization time were observed and compared.Results The serum PCT, WBC and hs-CRP levels pre-treatment in study group were higher than those in control group(P<0.05).The area under the ROC curve of PCT and hs-CRP was 1.000,respectively, and WBC was 0.804, there were significant difference between PCT and WBC (Z=5.250,P=0.000), between hs-CRP and WBC (Z=5.037,P=0.000).After treatment, the wounds of 23 case patients (92.00%) were cured in hyperbaric oxygen group, and 21 cases in routine group (84.00%) , there were no significant difference in cure rate between two groups.There were six cases(24.00%) of complications and one case (4.00%) of death in hyperbaric oxygen group,while nine cases (36.00%) of complications and two cases (8.00%) of death, there were no significant difference in complications rate and death rate between two groups.The hospitalization time in hyperbaric oxygen group was (39.17 ±6.73) d, which was significantly lower than (52.13 ±4.28) d in routine group(P<0.05).Conclusion PCT and hs-CRP have certain value in diagnosis of children with acute necrotizing fasciitis; incision and drainage combined with hyperbaric oxygen therapy has a better clinical effect in the treatment of children with acute necrotizing fasciitis.
7.Clinical, endoscopic and histopathological features of eosinophilic gastroenteritis in 76 children
Sufang YANG ; Min YANG ; Lanlan GENG ; Peiyu CHEN ; Gaoyang DUAN ; Hongli WANG ; Liya XIONG ; Sitang GONG
Chinese Journal of Digestive Endoscopy 2017;34(2):94-98
Objective To analyze the clinical, endoscopic and histopathological features of eosinophilic gastroenteritis ( EG) in children. Methods A retrospective study of 76 children with EG was performed to analyze clinical symptoms, laboratory and imaging results, endoscopic and pathological features, status of Helicobacter pylori ( H. pylori) infection, treatment and outcomes. Results The main clinical symptoms were abdominal pain in 55. 3%(42/76) cases, vomiting in 39. 5% (30/76) cases and hematochezia in 38. 2% cases( 29/76) . The hemoglobin level decreased significantly in 34 cases ( 44. 7%, 34/76). Peripheral blood eosinophil (EOS) count increased significantly in 9 cases (11. 8%,9/76) and EOS percentage increased significantly in 13 cases(17. 1%,13/76). Total serum IgE elevated in 32 cases ( 54. 2%, 32/59 ) . There were also 18 cases ( 36. 7%, 18/49 ) positive in serum allergen?specific immunoglobulin E ( sIgE) test and 25 cases ( 32. 9%,25/76) positive in fecal occult blood test. Among 51 cases of abdominal ultrasound examination, there were 7 cases of ascites, 4 cases of pelvis fluid and 3 cases of intestinal wall change. Endoscopic examination in 76 cases showed 63 cases ( 82. 9%) of mucosal hyperemia/edema,20 cases ( 26. 3%) of ulceration, 17 cases ( 22. 4%) of erosion, 11 cases ( 14. 5%) of nodularity or hyperplasia and 9 cases ( 11. 8%) of normal mucosa. The pathological examination showed mucosal inflammation with a large number of EOS infiltration(≥20 per HPF).There were 12 cases(15. 8%, 12/76) of H. pylori infection. Among the 76 cases, clinical symptoms improved significantly in 74 patients after treatment with dietary allergen avoidance, anti?allergy medications, antacids, montelukast and corticosteroid, and the total efficacy was 97. 4%. The efficacy of dietary allergen avoidance, anti?allergy medications, antacids and montelukast was 93. 8%( 61/65 ) . The efficacy of corticosteroid was 86. 7%(13/15). Conclusion The clinical manifestations and endoscopic characteristics of EG in children lack specificity. In terms of diagnosis, the elevated total serum IgE and the positive sIgE test may be taken as reference for the diagnosis of EG. The definite diagnosis is based on pathological examination ( EOS infiltration≥20 per HPF).While in terms of treatment, dietary allergen exclusion, anti?allergy medications, antacids and montelukast are highly effective, which can be taken as the first option. There is no need of corticosteroid as routine therapy.
8.Multicenter analysis of influence of Helicobacter pylori eradication on chronic gastritis
Jun FANG ; Yiqi DU ; Zhiqiang SONG ; Liya ZHOU ; Sanren LIN ; Xiaohua HOU ; Sanping XU ; Minhu CHEN ; Lishou XIONG ; Yanfang GONG ; Huagao ZHANG ; Li GAO ; Zhaoshen LI
Chinese Journal of Digestive Endoscopy 2011;28(8):433-437
Objective To evaluate the influence of Helicobacter pylori (Hp) eradication on clinical manifestations, endoscopic features and pathological findings of chronic gastritis. Methods This was a multiple-center, prospective and randomized cohort study. Patients with non-atrophy chronic gastritis from January 2009 to December 2010 were randomized into 3 groups as Hp positive group with eradication, Hp positive group without eradication and Hp negative group. Clinical manifestations, endoscopic findings and pathologic changes of inflammation were compared before and after administration of gastric mucosal protective agent for 8 weeks. Results A total of 211 patients were recruited. Changes of symptom score, endoscopic erosion and mucosal inflammation were significantly different before and after treatment in 3 groups. The decrease in symptom scores of eradication group was ( 3.56 ± 1.37 ), which was significantly higher than that of non-eradication group (2. 80 ± 1.30, P <0. 01 ). The decrease of mucosal inflammation and inflammatory activity scores in eradicate group was 1.08 ± 1.34 and 1.42 ± 1.09, respectively, which were also significantly higher than those of the eradication group (0. 49 ± 1.47 and 0. 61 ± 1.34, P <0. 01 ). But the improvement of endoscopic erosion in 2 groups showed no significant difference. There were no significant differences in these variables between non-eradication group and Hp-negative group ( P > 0. 05 ). Conclusion For chronic non-atrophic gastritis patients with positive Hp infection, combination of mucosal protective agents and Hp eradication can achieve better improvement in symptoms and gastric inflammation repair.
9. One pedigree analysis of a familial hypocalciuric hypercalcemia caused by a new heterozygous mutation in calcium-sensing receptor gene
Liya XU ; Fei WANG ; Yan GONG ; Sheng GUO ; Yongfen LYN ; Pin LI
Chinese Journal of Endocrinology and Metabolism 2018;34(7):583-586
Medical history and physical examinations were performed to assess the clinical manifestations and growth of one patient with familial hypocalciuric hypercalcemia(FHH). Clinical data, including histories of his parents and 3 maternal relatives were collected. Serum parathyroid hormone(PTH), calcium, phosphorus, 24-hour urinary calcium, and 24-hour urinary calcium to creatinine ratio(UCCR)were measured or calculated. Meanwhile, after peripheral blood samples were collected and genomic DNA was extracted, the whole exome sequencing to detect gene mutations of the proband was performed. Further family screenings were also performed by Sanger sequencing to assess the relationship between genotype and phenotype. The results showed that the proband with motor developmental delays had severe hypercalcemia(4.20 mmol/L), while his mother without clinical symptoms had a higher blood calcium within the normal range(2.57 mmol/L). However, their urinary calcium levels were both low(UCCR< 0.01). The C→T heterozygous missense mutation was found by exome sequencing at nucleotide 1243 within exon 4 of calcium sensing receptor(CaSR)gene in the proband, which caused a substitution of Arginine to Tryptophan(R415W). Sanger sequencing confirmed the same mutation in his mother. There was no mutation in other family members. (
10.Cryptotanshinone promotes brown fat activity by AMPK activation to inhibit obesity
Jie NI ; Aili YE ; Liya GONG ; Xiafei ZHAO ; Sisi FU ; Jieya GUO
Nutrition Research and Practice 2024;18(4):479-497
BACKGROUND/OBJECTIVES:
Activating brown adipose tissue (BAT) and browning of white adipose tissue (WAT) can protect against obesity and obesity-related metabolic conditions.Cryptotanshinone (CT) regulates lipid metabolism and significantly ameliorates insulin resistance. Adenosine-5'-monophosphate (AMP)-activated protein kinase (AMPK), a receptor for cellular energy metabolism, is believed to regulate brown fat activity in humans.MATERIALS/METHODS: The in vivo study included high-fat-fed obese mice administered orally 200/400 mg/kg/d CT. They were evaluated through weight measurement, the intraperitoneal glucose tolerance test (IPGTT), intraperitoneal insulin tolerance test (IPITT), cold stimulation test, serum lipid (total cholesterol, triglycerides, and low-density lipoprotein) measurement, hematoxylin and eosin staining, and immunohistochemistry.Furthermore, the in vitro study investigated primary adipose mesenchymal stem cells (MSCs) with incubation of CT and AMPK agonists (acadesine)/inhibitor (Compound C).Cells were evaluated using Oil Red O staining, Alizarin red staining, flow cytometry, and immunofluorescence staining to identify and observe the osteogenic versus adipogenic differentiation. Quantitative real-time polymerase chain reaction and the Western blot were used to observe related gene expression.
RESULTS:
In the diet-induced obesity mouse model mice CT suppressed body weight, food intake, glucose levels in the IPGTT and IPTT, serum lipids, the volume of adipose tissue, and increased thermogenesis, uncoupling protein 1, and the AMPK pathway expression. In the in vitro study, CT prevented the formation of lipid droplets from MSCs while activating brown genes and the AMPK pathway. AMPK activator enhanced CT’s effects, while the AMPK inhibitor reversed the effects of CT.
CONCLUSION
CT promotes adipose tissue browning to increase body thermogenesis and reduce obesity by activating the AMPK pathway. This study provides an experimental foundation for the use of CT in obesity treatment.