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In recent years， the role of quantitative pharmacological models in applicable population of drugs and dose optimization has been widely recognized. In order to improve the efficiency of clinical development and optimize clinical rational drug use， quantitative pharmacological models are being gradually introduced into the research of traditional Chinese medicine （TCM）. There are various types of quantitative pharmacological models， among which the following three models are commonly used：①Population pharmacokinetic （PPK） model， which is mainly used to explore the pharmacokinetic characteristics in different populations.②Pharmacokinetic-pharmacodynamic （PK-PD） model， which is used to reveal the internal relationship among dose， time and efficacy. ③PPK-PD model， which integrates both the characteristics of PPK model and PK-PD model. The paper summarizes the application of the above three models in TCM， and extracts the main ideas and methods of TCM model research， in order to provide reference for clinical research and rational use of TCM.
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Traditionally, it is believed that atopic dermatitis (AD) usually starts in infancy or childhood. However, adult-onset AD (adult-onset AD) occurring at the age of ≥ 18 years is not uncommon, but has not received due attention. There are overlaps and differences between adult-onset AD and childhood-onset AD in terms of genetic factors, triggers, pathogenesis, clinical manifestations, etc. It is undoubtedly of great practical significance to understand and accept the concept of adult-onset AD in clinical practice. However, there are many problems to be solved, especially the establishment of special diagnostic criteria and management models of adult-onset AD.
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OBJECTIVE@#To investigate the expression changes of the epigenetic regulator enhancer of zeste homolog 2 (EZH2) during pulp inflammation and the effect of EZH2 on macrophages migration.@*METHODS@#Rat dental pulp was stimulated with 10 g/L lipopolysaccharide (LPS) to establish a model of rat pulpitis at different stages of inflammation. Immunohistochemical staining was used to detect the expression changes of EZH2 during the progression of pulp inflammation. Immunofluorescence double staining was used to detect the expression of EZH2, CD68 and their colocalization. To screen the appropriate concentration of EZH2 recombinant protein to stimulate hDPCs and human leukaemia-derived monocytic cell line (THP-1) cells, the effects of different concentrations (1, 10, 20, 40, and 100 μg/L) of EZH2 recombinant protein on proliferation of human dental pulp cells (hDPCs) and human monocyte cell line THP-1 were detected by cell counting kit-8 (CCK-8). Transwell migration assay was used to detect the effect of supernatants of hDPCs treated with EZH2 recombinant protein on the migration of THP-1 cells.@*RESULTS@#HE staining results showed that in the model of rat pulp inflammation induced by LPS, with the prolongation of LPS stimulation, the inflammation response of pulp gradually increased. Immunohistochemical results showed that EZH2 expression decreased within 8 h of LPS-induced dental pulp inflammation; but after 1, 3, and 7 d of stimulation, EZH2 expression gradually increased with the extension of the stimulation time. As for the normal rat dental pulp tissue, the positive expression of EZH2 was scattered in the odontoblast cell layer and the pulp proper. Compared with the control group, LPS stimulated the expression of EZH2 and CD68 in the infected dental pulp, and the colocalization of EZH2 and CD68 could be detected in macrophages. The results of CCK-8 suggested that the appropriate concentration of EZH2 recombinant protein to stimulate hDPCs and THP-1 cells was 20 μg/L. Transwell cell migration assay confirmed that compared with the supernatant of EZH2 untreated HDPCs group, the supernatant of EZH2treated hDPCs significantly promoted macrophage chemotaxis.@*CONCLUSION@#EZH2 is involved in the development of pulpitis and promotes the chemotaxis of macrophages, which suggests that EZH2 may play an important regulatory role in the development of pulp inflammation.
Subject(s)
Animals , Humans , Rats , Cells, Cultured , Chemotaxis , Dental Pulp , Enhancer of Zeste Homolog 2 Protein , Inflammation , MacrophagesABSTRACT
Objective@#To investigate the incidence, mortality and clinical characteristics of neonatal necroti-zing enterocolitis(NEC) in Shanghai.@*Methods@#A retrospective study was conducted in 623 cases of NEC from January 2010 to December 2015 at Children′s Hospital of Fudan University.All analysis were performed by using the statistical software package Stata 12.0.@*Results@#Six hundred and twenty-three NEC neonates were included in the study, and 485 of them were preterm infants, including 304 cases of stage 1, 176 cases of stage 2 and 143 cases of stage 3.The gestational age was (33.2±3.9) weeks, and the birth weight was (1 979.7±813.5) g. The incidence of NEC in Children′s Hospital of Fudan University was 1.29% (410/31 662 cases), and that of the stage 2 and stage 3 was 1.01% (319/31 662 cases). The gestational age was smaller and birth weight was less in the stage 2 and stage 3 group than that in the stage 1 group (all P<0.001). The percentage of cases received breast milk feeding was 7%.The rate of prophylactic antibiotics within 3 days of their life and ibuprofen for patent ductus arteriosus prior to NEC in stage 1 group was lower than that in stage-2 and stage 3 groups (all P<0.05). The most common clinical presentations were abdominal distension(71.75%, 447/623 cases), decreased bowel sounds(56.02%, 143/623 cases), looked sick (45.43%, 283/623 cases) and bloody stools(40.45%, 252/623 cases). The bowel perforation rate of the preterm and the term infants was 17.73%(86/485 cases)and 13.04%(18/138 cases), respectively.The patients who received surgical management took up 25.36%.The neonates were most commonly complicated with post-NEC stenosis (10.27%) and a culture-proven sepsis(7.87%). The count of white blood cell (WBC)<4×109/L and platelet<100×109/L raising level in stage 2 and stage 3 were higher than those in stage 1(all P<0.05). The antibiotics used for NEC were metronidazole (69.34%), carbapenems (65.65%), cephalosporins(61.16%) and penicillins(58.59%). The prognosis of NEC showed that cure cases occupied 65.49%, discharged cases with a better condition 19.58%, and death cases occupied 14.93%.The mortality of stage 3 accounted for 45.46%.@*Conclusions@#Newborn NEC mainly had gestational age of 28-34 weeks and birth weight of 1 000-1 999 g, respectively.The incidence of NEC 1.29% and it is decreasing year by year, while that of very-low-birth weight(VLBW) is still as high as 11.82%.The mortality of NEC occupies 14.93%, while that of stage 3 reaches as high as 45.46%.
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Objective To investigate the incidence,mortality and clinical characteristics of neonatal necrotizing enterocolitis (NEC) in Shanghai.Methods A retrospective study was conducted in 623 cases of NEC from January 2010 to December 2015 at Children's Hospital of Fudan University.All analysis were performed by using the statistical software package Stata 12.0.Results Six hundred and twenty-three NEC neonates were included in the study,and 485 of them were preterm infants,including 304 cases of stage 1,176 cases of stage 2 and 143 cases of stage 3.The gestational age was (33.2 ± 3.9) weeks,and the birth weight was (1 979.7 ± 813.5) g.The incidence of NEC in Children's Hospital of Fudan University was 1.29％ (410/31 662 cases),and that of the stage 2 and stage 3 was 1.01％ (319/31 662 cases).The gestational age was smaller and birth weight was less in the stage 2 and stage 3 group than that in the stage 1 group (all P ＜ 0.001).The percentage of cases received breast milk feeding was 7％.The rate of prophylactic antibiotics within 3 days of their life and ibuprofen for patent ductus arteriosus prior to NEC in stage 1 group was lower than that in stage-2 and stage 3 groups (all P ＜ 0.05).The most common clinical presentations were abdominal distension (71.75％,447/623 cases),decreased bowel sounds (56.02％,143/623 cases),looked sick (45.43％,283/623 cases) and bloody stools(40.45％,252/623 cases).The bowel perforation rate of the preterm and the term infants was 17.73％ (86/485 cases)and 13.04％ (18/138 cases),respectively.The patients who received surgical management took up 25.36％.The neonates were most commonly complicated with post-NEC stenosis (10.27％) and a culture-proven sepsis (7.87％).The count of white blood cell (WBC) ＜ 4 × 109/L and platelet ＜ 100 × 109/L raising level in stage 2 and stage 3 were higher than those in stage 1 (all P ＜ 0.05).The antibiotics used for NEC were metronidazole (69.34％),carbapenems (65.65 ％),cephalosporins (61.16％) and penicillins (58.59％).The prognosis of NEC showed that cure cases occupied 65.49％,discharged cases with a better condition 19.58％,and death cases occupied 14.93％.The mortality of stage 3 accounted for 45.46％.Conclusions Newborn NEC mainly had gestational age of 28-34 weeks and birth weight of 1 000-1 999 g,respectively.The incidence of NEC 1.29％ and it is decreasing year by year,while that of very-low-birth weight (VLBW) is still as high as 11.82％.The mortality of NEC occupies 14.93 ％,while that of stage 3 reaches as high as 45.46％.
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Objective To study the correlation of necrotizing enterocolitis (NEC) and encephalopathy of prematurity (EOP) in premature infants with gestational age (GA) ＜ 32 weeks.Method From January 2009 to December 2014,clinical data of preterm infants (GA ＜ 32 weeks) admitted to department of neonatology of Children's Hospital of Fudan University and received brain magnetic resonance imaging (MRI) at corrected GA of full term or near full term were collected.NEC patients were assigned into the NEC group.At the same time,patients with similar GA and birth weight without NEC were assigned into the control group.The incidence and MRI characteristics of EOP were studied using Chi-square method.Result A total of312 preterm infants were included in our study,104 in the NEC group,and 208 in the control group.The incidence of EOP in the NEC group was higher than the control group (27.9％ vs.17.3％).The difference between the two groups were statistically significant (P =0.030).The incidence of non-cystic EOP in the NEC group was significantly higher than the control group (89.7％ vs.63.9％,P =0.017).Conclusion NEC and EOP may be correlated in preterm infants with GA ＜32 weeks.Most of EOP were non-cystic injury.
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Both bone morphogenetic protein 2 (BMP2) and the wingless-type MMTV integration site (WNT)/β-catenin signalling pathway play important roles in odontoblast differentiation and dentinogenesis. Cross-talk between BMP2 and WNT/β-catenin in osteoblast differentiation and bone formation has been identified. However, the roles and mechanisms of the canonical WNT pathway in the regulation of BMP2 in dental pulp injury and repair remain largely unknown. Here, we demonstrate that BMP2 promotes the differentiation of human dental pulp cells (HDPCs) by activating WNT/β-catenin signalling, which is further mediated by p38 mitogen-activated protein kinase (MAPK) in vitro. BMP2 stimulation upregulated the expression of β-catenin in HDPCs, which was abolished by SB203580 but not by Noggin or LDN193189. Furthermore, BMP2 enhanced cell differentiation, which was not fully inhibited by Noggin or LDN193189. Instead, SB203580 partially blocked BMP2-induced β-catenin expression and cell differentiation. Taken together, these data suggest a possible mechanism by which the elevation of β-catenin resulting from BMP2 stimulation is mediated by the p38 MAPK pathway, which sheds light on the molecular mechanisms of BMP2-mediated pulp reparative dentin formation.