As a depot drug delivery system, injectable polylactide-polyglycolide (PLGA) sustained-release microspheres have been successfully used to treat many diseases since the first microsphere product Lupron depot was approved for marketing in the United States in 1989. It has the ability of long-term release in the body for several days to several months, which can not only reduce the times of administration, but also reduce the drug blood concentration fluctuations, significantly improve the safety and patient compliance. In vitro-in vivo correlation (IVIVC) makes the development of microspheres more possible. It can describe the dynamic information of drug release in vivo through the in vitro release behavior of microspheres, and can reduce the workload of each stage and shorten the time span while characterizing the performance of microspheres. IVIVC can provide guidance or support for drug development, production changes, supervision and management. This article summarizes the release mechanism of injectable PLGA sustained-release microspheres, common measurement methods and theories of in vitro and in vivo release. And we also focus on the establishment and application of IVIVC, especially A level IVIVC in the field of microsphere preparations, to provide a reference for further study on in vitro-in vivo correlation of microspheres.

Objective To provide a basis for specific intervention by dynamic observation of the households'related health life behavior and the children fluorosis change trend caused by the coal-burning-borne endemic fluorosis in Pu'an County.Methods Three villages were chosen using simple random sampling method in 2011-2013 for continuous monitoring.Every monitoring year in each monitoring village,according to the principle of every household survey,10 households were selected to survey related health life behavior;,and in the monitoring village all the children aged 8-12 years old were selected for Diagnosis of Dental Fluorosis (WS/T 208-2001),and in each age group,10 urine samples (half male half female) were collected,the fluoride content was determined by the ion selective electrode method (WS/T 89-1996).Results In 2011-2013,the households stoves qualified rate,stoves correct usage rate and the corn or chili correct drying rate were all 100.00％ (30/30).The dental fluorosis incidences of 8-12 years old children were 63.60％ (332/522),25.44％ (173/680) and 14.29％ (80/560),respectively,decreased year by year (x2 =324.67,P ＜ 0.05).In 2011-2013,children urinary fluoride levels were 0.83,0.84 and 0.68 mg/L,respectively.The difference between years was statistically significant (x2 =26.89,P ＜ 0.05),and the level in 2013 was significantly lower than those of 2011 and 2012 (all P ＜ 0.01).Conclusion In 2011-2013,the residents in Pu'an have good health life behavior,and the condition of children's dental fluorosis is decreased year by year.

ObjectiveTo explore the effect of blocking the JAK/STAT signal pathway on the activity of Caspase-3 in the synovial tissue of rheumatoid arthritis rats.MethodsFifty rat models of collageninduced arthritis,which had arthritis index more than 2 were divided into the model group,the low dosage of AG490 group,the medium dosage of AG490 group and high dosage of AG490 group.Inaddition,6 rats were treated as normal control group.Normal saline,AG490 1,5,10 mg·kg-1 ·d-1 were given by intraperitoneal injection.Then the volume claws and pathologic scores of the rat models were recorded and the activity of Caspase-3 in the synovial tissue were compared.The results were analyzed by one-way ANOVA and LSD-t or Tamhane's T2 test.ResultsThe arthritis of the CIA models progressed fast,the volume of the claws and the pathological score of them were significantly higher than those of the control group.At the same time,no Caspase-3 positive express could be detected in the control group,whilethe model group had slightly increased expression.After different dosages of AG490 were applied,the swollen of joints was significantly improved compared with the model group.The histopathological score of the medium AG490 dosage of group and high dosage group(2.7±0.8,1.8+0.9) were remarkably decreased than those of the model group(4.3+1.2),the differences were statistically significant (P＜0.01).In addition,the Caspase-3 expression in the low,medium and high AG490 dosage group ( 1.90±0.15,3.13±0.33,3.56+0.34) was significantly higher than that of the model group(1.48±0.18)(P＜0.05 or P＜0.01 ).ConclusionBlocking JAK/STAT signal pathway can increase the activity of Caspase-3,reduce the excessive proliferation of synovial tissue,and improve arthritis symptoms.

Objective To analyze the clinical features and common etiology of lung nodules in children. Methods The etiology, diagnosis, radiological features from 98 hospitalized children of lung nodules were analyzed. Results Of them, 58 were male and 40 were female aged from 0.2 years old to 14.8 years old. Pulmonary infection were found in 41 cases (41.8%) including tuberculosis in 15 cases (15.3%), pulmonary fungal infection in 13 cases (13.3%), pneumonia in 11 cases (11.2%), lung trematode in 2 cases (2.0%). Pulmonary metastases were found in 28 cases (28.6%), multiple pulmonary arteriovenous fistula in 1 case (1.0%), and pulmonary contusion in 1 case (1.0%) and unknown etiology in 27 cases (27.6%). Conclusions The etiology of lung nodules is complicated, in which infectious diseases are the most commonly seen, followed by pulmonary metastases. Biopsy is the golden standard of diagnosis.

OBJECTIVETo investigate the impact of cyclosporine A (CsA) on atrial expression change of L-type calcium channel alpha1c subunit in a canine model of atrial fibrillation (AF).

METHODSAF was induced by rapid atrial pacing (400 beats/min) for 8 weeks in adult male dogs and placebo (n = 6) or CsA (5 mg x kg(-1) x d(-1), n = 6) were orally administered to these animals. Sham operated animals served as normal controls (n = 6). The atrial electrophysiological parameters including P wave duration, atrial effective refractory period (AERP) were recorded and analyzed at baseline and 8 weeks later. Animals were scarified at 8 weeks post final electrophysiological examinations and atrial expressions of L-type calcium channel alpha1c subunit were determined by Western blot.

RESULTSCompared to sham group, the P wave duration was significantly prolonged while AERP was significantly decreased in AF and CsA groups (all P < 0.05). AERP was significantly longer in CsA group than that in AF group (P < 0.05). L-type calcium channel alpha1c subunit expression was significantly downregulated in AF group compared to sham group (P < 0.05) and CsA significantly attenuated this downregulation (P < 0.01 vs. AF group).

CONCLUSIONCsA could attenuate the downregulation of the L-type calcium channel alpha1c subunit expression and improve the atrial electrophysiological remodeling in this canine model of AF.

Animals ; Atrial Fibrillation ; drug therapy ; metabolism ; Calcium Channels, L-Type ; metabolism ; Cyclosporine ; pharmacology ; therapeutic use ; Dogs ; Heart Atria ; metabolism ; physiopathology ; Male

Actins ; metabolism ; Angiomyolipoma ; metabolism ; pathology ; surgery ; Desmin ; metabolism ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Perivascular Epithelioid Cell Neoplasms ; metabolism ; pathology ; S100 Proteins ; metabolism ; Skin Neoplasms ; metabolism ; pathology ; surgery

This paper aims to construct a Bayesian(BN) fault diagnosis model of traditional Chinese medicine dry granulation based on the failure model and effect analysis(FMEA), effectively control risk factors and ensure the quality of granules.Firstly, the risk ana-lysis of dry granulation process was carried out with FMEA, and the selected medium and high risk factors were taken as node variables to establish corresponding BN network with causality.According to the mathematical reasoning method of probability theory, the model was accurately inferred and verified by Netica, and the granule nonconformance was used as the evidence for reversed reasoning to determine the most likely cause of the failure that affected the granule quality.The BN fault diagnosis model of traditional Chinese medicine dry gra-nulation was established based on the medium and high risk factors of process, prescription and equipment screened out by FMEA, such as roller pressure, raw material viscosity, clearance between rollers in the paper.The fault diagnosis of traditional Chinese medicine dry granulation process was then carried out according to the model, and the posterior probability of each node under the premise of nonconforming granule quality was obtained.This method could provide strong support for operators to quickly eliminate faults and make decisions, so as to improve the efficiency and accuracy for fault diagnosis and prediction, with innovation in its application.
Bayes Theorem ; Medicine, Chinese Traditional ; Probability

Background Our previous study demonstrated that curcumin can induce the apoptosis of retinal pigment epithelial (RPE) cells and herein inhibit the proliferation of RPE cells,and it is proved that the intravitreous injection of 0.1mg curcumin has less adverse effect to ocular tissue, inferring a good applicative prospect in clinic. Objective The goal of this experiment was to evaluate the effectiveness of curcumin on the prevention and treatment of experimental proliferative vitreoretinopathy (PVR). Methods PVR models were induced by injection of 0.1ml RPE cells (containing 2×106 cells) into vitreous cavity in 40 eyes of 20 healthy and mature New Zealand albino rabbits.0. 1ml curcumin(0. 1 mg) was then injected into lateral eye of each model rabbit immediately following the injection of RPE cells,and the equal volume of normal saline solution containing 0. 5‰ DMSO was injected into the fellow eye of each model rabbit as controls. On 1,3,7,14,21 and 28 days after injection, the changes of cornea, aqueous humor, lens, vitreous and fundus were examined and recorded by slit lamp biomicroscope, indirect ophthalmoscope,fundus color camera and B-type ultrasonograph to evaluate the inflammatory response. The incidence rate of retinal detachment was calculated and compared between curcumin group and control group. Results The inflammatory reaction in anterior chamber and misty opacity in vitreous were found from 1 day through 3 days after injection, but no obvious proliferative strap and retinal detachment in all of the experimental eyes. On the 7th day after injection, inflammatory reaction was extinct in the anterior chamber of rabbit eyes, and proliferative strap occurred in 14 eyes(75% ) in the control group but only 2 eyes (10% ) in curcumin group,showing significant difference between these two groups (P<0. 01). No retinal detachment was seen in both the two groups. On 14,21 and 28 days after injection, the incidence rate of retinal detachment was 55% ,80% ,95% respectively in control group and that of curcumin group was 10% ,15% ,15% respectively,presenting considerably differences between two groups (P<0. 01, P<0. 01 ,P<0. 01 ). Conclusion Injection of curcumin into vitreous cavity can effectively inhibit the occurrence and development of PVR in rabbit.

Objective To investigate the intelligence standard for diagnose the sub-cretin children and children with mental retardation of socio-cultural type.Methods The full intelligence quotient(IQ),verbal intelligence quotient(VIQ)and performance intelligence quotient(PIQ)was tested by Wechsler scale(C-WISC)for mild iodine deficiency disordem children,children living in abnormal socio-cultural condition and normal children aged 7～14 years old in Qinba mountain area.The test results had been compared between the groups.Results There were no significant difference between psychomotor functioning well children and children living normal sociocuhural condition in VIQ,PIQ and full IQ(89.24±18.44 vs 90.75±17.58,87.58±15.78 vs 88.95±15.56,87.42±17.84 vs 89.02±17.18,t=1.14,1.19 and 1.24,respectively,all P＞O.05).PIQ and full IQ were significantly lower in mild iodine deficiency disorders children than in children with abnormal socio-cultural background (65.81±10.22 vs 72.33±13.23,62.42±12.31 vs 68.13±14.54,t=3.26,2.55,P＜0.01 or＜0.05,respectively).But the VIQ was not significantly different between these two groups.The average difference of VIQ and PIQ among mild iodine deficiency disorders children wag-0.32 without significant difierence(t=0.28,P＞0.05),however it was-2.91 among children under abnormal socio-cultural condition with significant difierenee(t=-3.59,P＜0.01).Conclusions IQ for iodine deficiency disorders children is characterized by that VIQ is damaged in parallel with PIQ,while that in children under abnormal soeio-cuhural condition is marked by that VIQ is retarded more severely than PIQ,which ean be used as an intelligence standard for differentiating the sub-cretin children from children wjth socio-cuhural mental retardation.

Objective: To explore the effect of herb-partitioned moxibustion (HPM) on tight junctions (TJs) of intestinal epithelial cells in Crohn disease (CD) mediated by tumor necrosis factor-α (TNF-α)-nuclear factor kappa B (NF-κB)-myosin-light- chain kinase (MLCK) pathway. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into a normal control (NC) group, a model control (MC) group, an HPM group and a mesalazine (MESA) group, with 12 rats in each group. Trinitrobenzene sulfonic acid (TNBS) was administered to establish CD models. When the model was confirmed a success, the HPM group rats were treated with HPM at Tianshu (ST 25) and Qihai (CV 6), while the MESA group rats were given MESA solution by lavage. When the intervention finished, the colonic epithelial tissues were separated, purified and cultured in each group to establish the intestinal epithelial barrier model in vitro, and TNF-α was added (100 ng/mL) in the culture medium and maintained for 24 h to establish an increased epithelial permeability model. Transepithelial electrical resistance (TEER) was used to examine the permeability of the barrier; Western blot was used to observe the expressions of the proteins related to TJs of intestinal epithelial cells mediated by TNF-α-NF-κB-MLCK pathway; immunofluorescence staining was used to observe the expressions and distributions of tight junction proteins in the intestinal epithelium. Results: After TNF-α induction, compared with the MC+TNF-α group, the TEER value increased significantly in the HPM+TNF-α and MESA+TNF-α groups (both P<0.001); the expressions of nuclear factor kappa B (NF-κB) p65, MLCK, myosin light chain (MLC), tumor necrosis factor receptor-associated factor 6 (TRAF6) and receptor interaction protein-1 (RIP1) decreased significantly (P<0.01 or P<0.05), and the expression of zinc finger protein A20 (A20) increased significantly (P<0.01); the expressions of occludin, claudin-1, zonula occludens protein 1 (ZO-1) and F-actin also increased significantly (all P<0.01). Compared with the MESA+TNF-α group, the expressions of MLC, occludin, claudin-1, ZO-1 and F-actin increased significantly in the HPM+TNF-α group (P<0.01 or P<0.05). Conclusion: HPM can protect or repair the damage of intestinal epithelial barrier in CD rats, which may be achieved through modulating the abnormal TJs in intestinal epithelium mediated by TNF-α-NF-κB-MLCK pathway.