The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates gene expression in a range of cells, including immune and epithelial cells. AhR signaling plays important roles in the immune system in both health and disease states. Tapinarof is a first-in-class small-molecule topical therapeutic AhR modulating agent launched for the treatment of psoriasis. To improve the activity and chemical stability of Tapinarof, a series of 2-phenylchromen-4-one derivatives were designed, synthesized and evaluated as novel AhR agonists. Compounds 5a, 5c, 5e and 5f potently activated AhR with an EC₅₀ value of 7, 9, 6 and 6 nmol·L^-1, respectively, which are 10-14 fold more potent than Tapinarof. Compounds 5a and 5e exhibit comparable inhibitory effects on IFN-γ production as Tapinarof. Furthermore, compounds 5a-5f exhibited favorable photochemical stability compared to Tapinarof. The compounds may eventually serve as lead compounds for the development of new AhR agonists.

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.

A new device that allows noninvasive measurement of venous pressure has been invented in our laboratory and tested for its feasibility and validity. The device consists of four parts: 1. the air infusion system; 2. the pressure sensor gauge; 3. signal transducer and data processing system 4. the fixing apparatus. The correlation between noninvasive pressure and invasive pressure has been studied in vitro test on a saphenous vein model and in vitro test on dog's portal venous system. In vitro and vivo study, an excellent correlation between noninvasive pressure and invasive pressure was obtained(r = 0.99, P < 0.0005; r = 0.97, P < 0.005). These data suggest that the new device allows a noninvasive measurement of venous pressure especially for the large veins such as vena cava, venae pulmonales and esophageal varices.
Animals ; Blood Pressure Determination ; instrumentation ; Dogs ; Equipment Design ; In Vitro Techniques ; Venous Pressure ; physiology

OBJECTIVETo study the relationship of bodyweight gain and the occurrence of gestational diabetes mellitus (GDM) during pregnancy, and analyze the effect of the nutritional therapy on the outcome of GDM.

METHODSWe collected 265 pregnant women who were diagnosed to be GDM and 571 pregnant women as the control group in the Xiamen Maternal and Child Health Hospital during 2007 - 2009. The general information of the subjects were collected. The bodyweight of the subjects were measured before the 20(th) week of pregnancy, 26 - 27(th) week (mid-gestation), 35 - 36(th) week (late-gestation) of pregnancy and prior to delivery. The bodyweight gain of different pregnancy weeks of the two groups and the effect of bodyweight on GMD occurrence before 28(th) week of pregnancy were analyzed by ages (< 25, 25-, 30-, ≥ 35). Meanwhile, we prescribed the nutrition therapy to the GDM pregnant woman and the effect of the blood sugar control on the outcome of the pregnancy were evaluated.

RESULTSThe bodyweight gain of 25-, 30-, older than 35 year-old subjects of the GDM group were (16.9 ± 6.3), (16.8 ± 6.1), (16.5 ± 6.0) kg, respectively, the bodyweight gain of the control group were (13.9 ± 3.0), (13.8 ± 2.7), (13.3 ± 2.7) kg (t = 6.259, 5.885, 3.533, respectively, all P values < 0.05). During the 20(th) to 27(th) week of the pregnancy, the bodyweight gain of the subjects younger than 25, 25-, 30-year-old in GDM group were (5.2 ± 1.0), (5.4 ± 1.7), (4.8 ± 1.3) kg, respectively, the bodyweight gain of the control group were (3.3 ± 1.3), (3.7 ± 1.6) and (3.5 ± 0.7) kg (t = 5.026, 9.659, 11.19, respectively, all P values < 0.05). During the period between 26(th) to 36(th) week, the bodyweight gain of subjects older than 35 year-old in GDP group was (3.6 ± 2.0) kg which was less than the control group ((4.0 ± 0.9) kg, t = -2.449, P < 0.05). 41.22% (54/131) and 44.94% (40/89) of 25-, 30-year-old subjects in GDM group showed bodyweight gain more than 13 kg, but 30.04% (76/253) and 26.07% (55/211) in the control group (OR values were 1.633 and 2.315, both P values < 0.05). The rate of the abnormal birth weight of the GDM group with blood sugar controlled and the control group were 6.6% (12/182) and 9.4% (54/571) which was lower than the GDP group with blood sugar control failure (20.5% (17/83)) (χ(2) values were 11.460, 9.119, respectively, both P values < 0.0125). The rate of premature delivery was 21.7%(18/83), higher than the control group (10.8%, 62/571) (χ(2) = 7.945, P < 0.0125). The rate of the cesarean in the control group was 25.4%(145/571) which was lower than the two GDM groups, including the group which the blood sugar was well controlled (46.7%, 85/182) and not well controlled (65.0%, 54/83) (χ(2) values were 29.540, 53.860, respectively, both P values < 0.0125).

CONCLUSIONThe bodyweight gain in the mid-gestation could affect the occurrence of GDM. The bodyweight gain should be less than 13 kg before 28(th) week of the pregnancy whose age was 25-year-old. Nutritional therapy and blood sugar control in GDM pregnant women could improve the pregnancy outcome.

Adult ; Blood Glucose ; Case-Control Studies ; Diabetes, Gestational ; diet therapy ; Female ; Humans ; Nutrition Therapy ; Pregnancy ; Pregnancy Outcome ; Treatment Outcome ; Weight Gain

OBJECTIVETo study the mechanism of microelement including Cu and Zn on the accumulation of three danshinones in Salviae miltiorrhizae root and build a theory basis for its good quality and high yield.

METHODSand culture experiments were conducted to study the effect of Cu and Zn on the accumulation of three danshinones and oxidase including peroxidase and polyphenol oxidase activity in the plant root. The correlation between available Cu and Zn contents in matrix and oxidase activity in the plant root and, the correlation between available Cu and Zn contents in matrix and contents of tanshinones in the root were discussed.

RESULTContents of danshinones in the root increased with the increasing of Cu and Zn concentration. Dynamic monitoring on contents of dan-shinones of the plant roots growing in the pots with different Cu and Zn concentration in the whole growing season showed that the contents of danshinones for 60 days were the lowest, for 120 days the highest and then dropped for 150 days. In addition, among available Cu and Zn contents of matrix, oxidase including peroxidase and polyphenol oxidase activity and contents of tanshinones in the root,the correlation between two factors were significant difference (P < 0.05 or P < 0.01).

CONCLUSIONThe mechanism of Cu and Zn on the accumulation of danshinones may be that Cu and Zn improve the activity of peroxidase and polyphenol oxidase, which promote transformation of phenolic compounds to terpenes and therefore to increase contents of danshinones.

Catechol Oxidase ; metabolism ; Copper ; metabolism ; Diterpenes, Abietane ; Drugs, Chinese Herbal ; analysis ; metabolism ; Peroxidase ; metabolism ; Phenanthrenes ; metabolism ; Plant Proteins ; metabolism ; Salvia miltiorrhiza ; enzymology ; metabolism ; Zinc ; metabolism

Objective To investigate the CT findings of Madelung's disease in the head and neck region,and to evaluate the value of CT in demonstrating the Madelung's disease in the head and neck region.Methods CT findings of Madelung's disease in the head and neck region in 7 cases were analyzed retrospectively.All were males,with the age from 36 to 60 years,mean 51 years.All patients were underwent CT native scan,and enhanced CT scan was performed on 3 of them.Results CT images in the neck of all patients showed accumulation of nonencapsulated fat within the subcutaneous tissue and(or) deep to the platysma,and(or)within the spaces between the muscles.The fat deposits were ill-defined and symmetrical.In most cases the fat deposits involved the anterior part of the neck(infrahyoid and suprahyoid),submandibular region,the subcutaneous tissue of the nape and deep to the stenomastoid muscles.Conclusions Madelung's disease in the head and neck region have characteristic CT findings,and CT has great value in qualitative and quantitative diagnosis in Madelung's disease.

Objective To study the influence on the tumor after percutaneous intra-tumor injection of ~(32)P-GMS in liver cancer as well as its suitable dose.Methods 24 New Zealand rabbits were used to establish the animal model of VX-2 liver cancer,and divided into A,B,C and D groups with individually 37,74,111 and 148 MBq of ~(32)P-GMS being injected,respectively;and then pathological changes of tumor were observed by light and electron microscope respectively.Result The dose of ~(32)P-GMS was obviously correlated with the radioactivity damage of tumor cells.In the A and B groups,the tumor cells were not observed to disappear completely after injection of ~(32)P-GMS,but in C group,tumor cells were almost completely disappeared and surrounded by a lot of connective tissue.Although the tumor cells were found to disappear completely in D group,normal liver tissues were also involved.Conclusion Percutaneous intra-tumor injection of ~(32)P-GMS with suitable dose that may induce the tumor tissue to be maximally damaged and may also provide some significances to prevent the tumor metastasis.

OBJECTIVETo investigate the diagnostic accuracy of flexirigid thoracoscopy for pleural diseases and the patients' compliance.

METHODSForty-seven patients with pleural effusion and thickening of unknown etiology underwent examinations with flexirigid thoracoscopy with subsequent pathological examination, and the diagnostic accuracy and the patients' compliance were observed.

RESULTSThoracoscopy identified lesions in the pleural and/or diaphragm in 42 patients and no lesions in 5 patients. Malignancy was confirmed in 21 (44.7%), tuberculosis in 17 (36.2%), idiopathic hypereosinophilic syndrome in 1 (2.1%), nocardiasis in 1 (2.1%), constrictive pericarditis in 1 (2.1%), chronic empyema in 2 (4.3%), splenic artery embolization in 1 (2.1%), and negative result in 3 (6.4%) of the cases. The diagnostic accuracy rate of flexirigid thoracoscopy reached 93.6%, and no serious complications in relation to the examination was found.

CONCLUSIONFlexirigid thoracoscopy is efficient and relatively safe for diagnosis of pleural diseases with or without hydrothorax.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Pleural Diseases ; diagnosis ; pathology ; Thoracoscopy ; adverse effects ; methods ; Young Adult

OBJECTIVETo explore the efficacy and safety of endoscopic submucosal enucleation (ESE) for gastric submucosal tumors (SMTs) originated from muscularis propria.

METHODSA total of 116 patients with gastric SMT originated from muscularis propria underwent ESE in Department of Gastroenterology of the Taizhou Hospital between July 2006 and March 2011. The occurrence of intra-operative and post-operative complications and corresponding treatment were recorded. After the treatment of ESE, the patients were followed up endoscopically.

RESULTSThe success rate of operation was 96.6%. The mean time of the procedure was (51.9±16.3) min. Complications included intra-operative bleeding (n=9, 7.8%), perforation (n=20, 17.2%), and post-operative bleeding (n=3, 2.6%). Among them, 5 cases (4.3%) required surgical intervention. None of patient had other complications such as peritoneal abscess or peritonitis. The mean hospitalization time after ESE was 6.1 days. The median follow-up period was 12 months (range, 3-48 months) and there was no residual tumor or recurrence.

CONCLUSIONESE is a safe and feasible treatment for patients with gastric SMT originated from muscularis propria.

Adult ; Female ; Follow-Up Studies ; Gastrectomy ; methods ; Gastroscopy ; methods ; Humans ; Male ; Middle Aged ; Stomach Neoplasms ; surgery ; Treatment Outcome

OBJECTIVETo investigate the molecular mechanism of adiponectin inhibiting activation of hepatic stellate cells in non-alcoholic fatty liver fibrosis.

METHODSThe rat models of non-alcoholic fatty liver fibrosis were successfully established by fat-rich diet administration. The expression of adiponectin mRNA and protein were respectively detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. LX-2 cells were cultured in an adipogenic differentiation mixture to induce quiescent adipocytic phenotypes, and then they were treated with TGFβ1, adiponectin and TGFβ1 + adiponectin, respectively. RT-PCR and Western blot were used to determine the expressions of mRNAs and proteins of a-smooth muscle actin (a-SMA), Collagen, adenosine monophosphate-activated protein kinase (AMPK), inducible nitric oxide synthase (iNOS), and endothelial NOS (eNOS). The results were analyzed using one-way ANOVA, Student-Newman-Keuls test, and linear correlation analysis. A P value of less than 0.05 was considered as statistically significant.

RESULTSIn vivo, with the progress of non-alcoholic fatty liver fibrosis, the model rats gradually showed hepatic steatosis, inflammation, necrosis and fibrosis. Compared with the control group, the level of serum adiponectin (2.49 ± 0.86 vs 5.81 ± 0.87, P < 0.05) and hepatic expressions of adiponectin mRNA and protein (0.26 ± 0.04 vs 0.72 ± 0.08; 0.64 ± 0.07 vs 0.21 ± 0.07, all P < 0.05) were all decreased in the 24th week group, and were negatively correlated with the level of Collagen which increased gradually. In vitro, TGFβ1 could activate quiescent LX-2 cells by decreasing mRNA and protein expression of eNOS (0.30 ± 0.10 vs 0.44 ± 0.08; 0.30 ± 0.09 vs 0.46 ± 0.07, all P < 0.05) and increasing the expression of iNOS (0.53 ± 0.07 vs 0.37 ± 0.04; 0.55 ± 0.07 vs 0.39 ± 0.05, all P < 0.05). Recombinant adiponectin not only maintained the quiescent phenotype of LX-2 cells but also inhibited LX-2 cells activation due to TGFβ1 by increasing the expression of eNOS (0.43 ± 0.08 vs 0.30 ± 0.10; 0.42 ± 0.07 vs 0.30 ± 0.09, all P < 0.05) and phosphorylation of AMPK (0.43 ± 0.07 vs 0.24 ± 0.04, P < 0.05) and decreasing the expression of iNOS (0.44 ± 0.05 vs 0.53 ± 0.07; 0.46 ± 0.07 vs 0.55 ± 0.07, all P < 0.05).

CONCLUSIONSData suggested that adiponectin could play a protective role on the pathogenesis of non-alcoholic fatty liver fibrosis by inhibiting the activation of hepatic stellate cells via up-regulating the expression of eNOS, which might associate with increased phosphorylation of AMPK.

Adiponectin ; metabolism ; pharmacology ; Animals ; Disease Models, Animal ; Fatty Liver ; metabolism ; Hepatic Stellate Cells ; metabolism ; Liver Cirrhosis ; metabolism ; pathology ; Nitric Oxide Synthase Type III ; metabolism ; Non-alcoholic Fatty Liver Disease ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Transforming Growth Factor beta1 ; metabolism ; pharmacology