OBJECTIVE: To develop colon-targeting multi-dosage oral delivery system (mini tablet) using chitosan as the material for treatment of colon cancer. METHODS: Indomethacin (IN) was chosen as a model drug. Firstly, IN solid dispersion was prepared, then Eudragit-chitosan bilayer coated colon targeting mini tablets were prepared by direct compression method and coating technology. The release profiles of the targeting mini tablets in different release media were studied. Small animal in vivo fluorescence imaging investigation was used to sudy the transport and absorption in rats. Beagle dogs were used as animal model to study the pharmacokinetics and bioavailability of the mini tablets. RESULTS: The Eugragit-chitosan bilayer coated mini tablets maintained complete form when passing through the stomach and small intestine of rats, and targeted to the colon. The pharmacokinetic data in Beagle dogs showed that the mini tablets had delayed release and preserved steady absorption. CONCLUSION: The prepared Eudragit-chitosan bilayer coated multi dosage oral colon mini tablets showed good colon targeting effect and sustained release, which can provide important reference for the treatment of colon diseases.

Developmental changes in children can affect drug disposition and clinical effects. A physiologically-based pharmacokinetic (PBPK) model is a mathematical model that can be used to predict blood drug concentrations in children and gain insight into age-dependent physiological differences in drug disposition impact. Pediatric PBPK (P-PBPK) models have attracted attention over the past decade. With the concerted efforts of academia, pharmaceutical companies, and regulatory agencies, there are more and more examples of pediatric clinical studies using PBPK models. Nevertheless, the number of P-PBPK models and their predictive performance still lag behind adult models. By referring to the literature, we study the process of children adapting to adult absorption, distribution, metabolism, and excretion (ADME) parameters and analyze the general principles of P-PBPK model establishment. In addition, we summarize the functions and application examples of commonly used P-PBPK modeling software to provide a basis for the rational application of modeling software.

OBJECTIVE: To investigate the eliminating ability of catechin to eliminate O2-* and *OH. METHODS: The ability of catechin to clear away O2-* and *OH was respectively measured by faintness chemiluminescence and spin trapping assay. RESULTS: IC50 that catechin eliminated O2-* and *OH was 6.16, 0.59 g/mL respectively, and the eliminating ability of catechin was much stronger than that of the extract from liquorice, rosemary, grape pip, giant knotweed and ginkgo leaf. CONCLUSION Compared with several important natural plants of antioxidants, the eliminating ability of cathechin is the best.
Antioxidants ; pharmacology ; Catechin ; pharmacology ; Free Radical Scavengers ; pharmacology ; Hydroxyl Radical ; metabolism ; Luminescent Measurements ; Superoxides ; metabolism

BACKGROUND: Acetabulum anterior column shape is complex, and closed to femoral artery, and femoral nerve. Fixed screws easily went into the acetabulum. Currently, there was less data on quantitative anatomy data of pelvic acetabulum fracture with anterior column plate internal fixation. OBJECTIVE: To compare the pelvis gender differences by analyzing digital anatomical features of normal adult acetabulum anterior column section through digital three-dimensional reconstruction and measurement. METHODS: Totally 30 normal adults (half male and half female) received pelvic CT scans, and data were obtained. Using Materialise Mimics Innovation Suite 16.0 software, the boundary of the pelvis was used as reference line for sectioning. The obturator groove, iliopubic eminence, anterior inferior iliac spine, and the anterior superior iliac spine were used as a reference mark. In 15 males and 15 females (30 sides), the corresponding boundary line from obturator groove to the anterior superior iliac spine of acetabular anterior column was sliced into 5 mm-thick sections. The tangent line was vertical to the boundary line. The tangent plane was vertical to the upper plane of the anterior column. The angle and length of each section 5, 10, 15 mm points from the boundary line to the acetabulum, and the perpendicular distance from anterior and posterior edges of the acetabulum to anterior inferior iliac spine, iliopubic eminence and the pubic tubercle. RESULTS AND CONCLUSION: (1) Acetabular anterior column from the obturator groove to the anterior superior iliac spine section was not significantly different (P > 0.05). (2) No matter in males or females, the tangent angle of the fifth layer section was minimum, and the tangent length of the sixth layer section was longest. The length and angle of the second slice at 5 mm point were not significantly different between males and females. However, above indexes in others were significantly larger in females than in males (P < 0.05). (3) Results indicated that in different fracture ranges and different fixation plate positions, the angle and length of pedicle screws are dynamic, so we only selected in accordance with above range, but cannot fix in a certain value. The design of the most accurate and effective placement angle and length should be aimed at nailing design parameters for each individual patient. The use of Mimics software can be used for three-dimensional reconstruction of CT data of adult acetabular anterior column fracture, and can measure the number of indexes, and provide a theoretical reference for the clinical diagnosis and treatment of acetabular anterior column fracture.

OBJECTIVETo explore the status of glucometabolic abnormalities in cardiological outpatients without previous diabetes diagnosis and with coronary artery disease (CAD) and hypertension.

METHODSPatients without previous diagnosis of diabetes but with hypertension and CAD aged 18 years or above were recruited from cardiology departments of 11 general hospitals in China. Demographic data, disease diagnosis and medical history were collected. Physical examination and questionnaire survey were performed after the random blood glucose test. Oral glucose tolerance test (OGTT) examination was made for patients with fasting blood glucose ≥ 6.1 mmol/L or postprandial random glucose ≥ 7.8 mmol/L. Adjusted prevalence rates were used in the study.

RESULTSA total of 7778 patients were included in 11 centers. After preliminary screening by fasting blood glucose and random blood glucose tests, 3861 patients were required to take OGTT, and 3019 (78.2%) patients actually took the test. 1287 out of 3019 patients screened with OGTT were diagnosed with diabetes, and the adjusted diabetes prevalence rate was 18.64% (1287/6904). The prevalence rate of diabetes was 19.87% (95/478), 9.22% (352/3819) and 14.81% (153/1033) in patients with CAD, hypertension, and CAD combined with hypertension, respectively. A total of 996 patients were diagnosed with impaired glucose tolerance (IGT) and its prevalence was 14.43% (996/6904). Of the enrolled population, 153 patients with random blood glucose lower than 7.8 mmol/L were also screened with OGTT test, 26.14% (40/153) patients met the diagnostic criteria of diabetes.

CONCLUSIONA high prevalence of diabetes is found in patients without previous diagnosis of diabetes and with hypertension and CAD consulting at cardiology departments. We thus suggest to perform OGTT in this patient cohort to improve the early diagnosis of IGT and diabetes, and prevent missed detection of type 2 diabetes mellitus or IGT in cardiovascular patients with normal fasting blood glucose. Our results indicate that it was feasible to use OGTT as a screening tool for detecting diabetes in these patients and the patient compliance is satisfactory.

Blood Glucose ; metabolism ; Coronary Disease ; complications ; Diabetes Mellitus, Type 2 ; complications ; diagnosis ; Female ; Glucose Tolerance Test ; Humans ; Hypertension ; complications ; Male ; Mass Screening ; Outpatients

ObjectiveTo investigate the clinical features of systemic lupus erythematosus (SLE) patients with fever and find out the related factors.MethodsData was collected by the same methods in the past ten years in fifteen hospitals in Jiangsu province and then the data wereretrospectively analyzed.The potentially possible risk factors of fever in SLE were selected and then analyzed by chi-square test,Wilcoxon rank sum test and Logistic regression analysis.ResultsAll 1762 patients were investigated.Seven hundred and twenty-nine had active fever.Age at hospitalization,initially treated patients,photosensitivity,serositis,nervous system involvement,generalized lymphadenopathy/hepatosplenomegaly,white blood cell count (WBC),haemoglobin (HB),erythrocyte sedimentation rate (ESR),C-reaction protein (CRP),alanine aminotransferase(ALT),albumin(ALB),serum creatinine (Scr),complement C3,anti-dsDNA antibodies positive rate,anti-Sm antibodies positive rate,SLEDAI score and past therapies were factors associatedwith SLE fever.Logistic regression analysis showed that abnormal WBC count (OR=1.396,95％CI 1.114-1.711,P=0.004),CRP(OR=1.005,95％CI 1.002-1.009,P=0.002),ALT(OR=1.003,95％CI 1.001-1.005,P=0.005),Scr (OR=0.997,95％CI0.995-0.999,P=0.007),HB (OR=0.986,95％CI 0.981-0.992,P=0.000),age (OR =0.984,95％ CI 0.974-0.993,P=0.001 ) and past usage of cyclophosphamide (CTX) (OR =0.557,95％CI 0.382-0.813,P=0.002) were correlated with SLE fever.ConclusionFever is one of the most common clinical manifestations of SLE patients.Leucopenia,elevated CRP levels,liver function abnormalities,anemia,younger age are risk factors for SLE fever,while renal impairment and past usage of CTX are protective factors.

OBJECTIVETo investigate the correlation of MDR1 and ABCG2 genetic polymorphisms with the efficacy and adverse events of irinotecan chemotherapy in patients with colorectal cancer (CRC).

METHODSClinical data of CRC patients treated with irinotecan-based chemotherapy in the Peking University Cancer Hospital between January 1996 and December 2011 were collected, and their blood samples were collected accordingly. Genomic DNA was extracted from blood samples. The following SNP detection of MDR1 and ABCG2 genes was conducted by direct sequencing method. The correlation of genetic SNPs with efficacy and toxicity of irinotecan treatment was further analyzed.

RESULTSAllele frequencies of MDR1 2677 G>T/A, ABCG2 421 C>A, 34 G>A, 376 C>T were comparable with previous studies. Genetic SNPs results from peripheral blood samples and tumor tissues were highly consistent. Patients carrying MDR1 2677 wild type had higher clinical benefit than those carrying mutant genotype, while the differences were not significant. The progression-free survival (PFS) was longer in wild-type patients as compared to mutant-type patients in second-line chemotherapy (P=0.012). There were no significant correlations between ABCG2 421 C>A, 34 G>A, 376 C>T and chemotherapy efficacy. No significant correlations were observed between MDR1 2677 G>T/A, ABCG2 421 C>A, ABCG2 34 G>A, ABCG2 376 C>T and irinotecan-related grade 3 and 4 neutropenia or diarrhea.

CONCLUSIONMDR1 2677 G>T/A may be served as a biomarker in predicting the efficacy of irinotecan chemotherapy in patients with colorectal cancer.

ATP Binding Cassette Transporter, Sub-Family B ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; genetics ; ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; Adult ; Aged ; Camptothecin ; analogs & derivatives ; therapeutic use ; Colorectal Neoplasms ; drug therapy ; genetics ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Proteins ; genetics ; Polymorphism, Single Nucleotide ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVE: To explore the effect and possible mechanism of catechin microcapsulation on the repair of DNA damage in glumreular mesangial cells (GMCs) induced by H2O2. METHODS: According to H2O2 concentration, the experiment GMCs were divided into 6 groups: a control group, 50 micromol/L group, 100 micromol/L group, 150 micromol/L group, 200 micromol/L group and 250 micromol/L group. Each group was sub-divided into 3 groups: 6 h group, 12 h group and 24 h group, in order to determining the optimum dose and the best time of detecting the DNA damage in GMCs. The cultured cells were divided into 8 groups as follows: the NS control group, the H2O2 group, the catechin groups (the final concentrations were 10.0, 15.0, and 20.0 mg/L respectively) and the various catechin microcapsulation groups (the final concentrations were 10.0, 15.0, and 20.0 mg/L respectively). At the end of the experiment, hydroxy radical (OH), malonydialdehyde (MDA) and total superoxide dismutase (tSOD) concentration of supernadant in GMCs were determined by biochemistry assay, the repair of DNA damage in GMCs were detected by single cell gel electrophoresis assay. RESULTS: (1)At 6th h, H2O2 of 100 micromoL/L could cause the DNA damage of GMCs, and H2O2 of 150 micromol/L could result in DNA damage significantly. (2) No difference was found in the comet span of GMCs DNA in the catechin group and catechin microcapsulation group of different concentrations, while the DNA comet tail-long in the catechin microcapsulation group was shorter than that of the catechin group(all P(s)<0.05), and the fluorescence intensity of tail in the catechin microcapsulation group was lower than that of the catechin group(all P(s)<0.01). (3)When the concentration of catechin was 10.0 mg/L, no statistical significance was obtained in the concentration of dOH-, MDA and tSOD between the catechin microcapsulation group and the catechin group; while dOH- and MDA concentrations were lower, and the tSOD was higher in the catechin microcapsulation group than that in the catechin group when the concentration of catechin was 15.0 mg/L and 20.0 mg/L(all P(s)<0.05). CONCLUSION Catechin microcapsulation can enhance the GMCs ability of repairing DNA damage,which may be due to elevating the capacity of its anti-oxidation by catechin microcapsulation.
Animals ; Capsules ; Catechin ; pharmacology ; Cells, Cultured ; Comet Assay ; DNA Damage ; drug effects ; DNA Repair ; drug effects ; Dose-Response Relationship, Drug ; Hydrogen Peroxide ; toxicity ; Hydroxyl Radical ; metabolism ; Malondialdehyde ; metabolism ; Mesangial Cells ; drug effects ; metabolism ; pathology ; Rats ; Superoxide Dismutase ; metabolism

Background and Objectives: Chronic inflammation of bone tissue often results in bone defects and hazards to tissue repair and regeneration. Cannabidiol (CBD) is a natural cannabinoid with multiple biological activities, including anti-inflammatory and osteogenic potential. This study aimed to investigate the efficacy and mechanisms of CBD in the promotion of bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation in the inflammatory microenvironment. Methods: and Results: BMSCs isolated from C57BL/6 mice, expressed stem cell characteristic surface markers and pre-sented multidirectional differentiation potential. The CCK-8 assay was applied to evaluate the effects of CBD on BMSCs’ vitality, and demonstrating the safety of CBD on BMSCs. Then, BMSCs were stimulated with lipopolysaccharide (LPS) to induce inflammatory microenvironment. We found that CBD intervention down-regulated mRNA expression levels of inflammatory cytokines and promoted cells proliferation in LPS-treated BMSCs, also reversed the protein and mRNA levels downregulation of osteogenic markers caused by LPS treatment. Moreover, CBD intervention activated the cannabinoid receptor 2 (CB2) and the p38 mitogen-activated protein kinase (MAPK) signaling pathway. While AM630, a selective CB2 inhibitor, reduced phosphorylated (p)-p38 levels. In addition, AM630 and SB530689, a selective p38 MAPK inhibitor, attenuated the enhancement of osteogenic markers expression levels by CBD in inflammatory microenvironment, respectively. Conclusions CBD promoted osteogenic differentiation of BMSCs via the CB2/p38 MAPK signaling pathway in the inflammatory microenvironment.

ObjectiveTo observe the clinical efficacy of Tongfu Xiezhuo enema in treating stage 3-4 chronic kidney disease （CKD） and the effect of the therapy on the neutrophil-to-lymphocyte ratio （NLR） as an inflammation marker. MethodSixty patients diagnosed with stage 3-4 CKD who visited the Nephrology Department of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from December 2022 to June 2023 were included and randomly assigned into observation and control groups in a ratio of 1∶1. The control group received conventional therapy plus Shenkang suppositories， while the observation group received conventional therapy plus Tongfu Xiezhuo enema. After 8 weeks of treatment， the clinical efficacy was assessed based on the changes in traditional Chinese medicine （TCM） symptom scores， renal function indicators， and NLR. Result① Both groups showed decreases in TCM symptom scores after treatment （P<0.01）， and the decreases were more significant in the observation group than in the control group （P<0.05）. The total response rate of TCM symptoms in the observation group was 79.31% （23/29）， which was higher than that （62.96%， 17/27） in the control group （Z=0.604，P<0.05）. ② After treatment， the observation group showed declined serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， and cystatin C （Cys C） and increased glomerular filtration rate （GFR） （P<0.01）， and the control group showed lowered SCr level and increased GFR （P<0.05）. The observation group had lower SCr level and higher GFR than the control group after treatment （P<0.05）. The total response rate of renal function in the observation group was 79.31% （23/29）， which was higher than that （55.56%， 15/27） in the control group （Z=1.127，P<0.01）. ③ The NLR in the observation group decreased after treatment （P<0.05）， and it was lower than that in the control group （P<0.05）. ④ There were no significant differences in safety indicators between the two groups before and after treatment. ConclusionTongfu Xiezhuo enema ameliorated symptoms and improved renal function indicators in the patients with stage 3-4 CKD by reducing the NLR and inhibiting inflammation.