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.

Objective: To investigate the influencing factors for myopia among primary and secondary school students in Suzhou, so as to provide basis for myopia prevention and control. Methods: The students in Grade 4-12 were recruited by stratified cluster random sampling method. Gender, grade, parents＇ myopia history, outdoor activity time and video display terminal time were collected through the questionnaire of National Surveillance Program of Influencing Factors for Common Diseases and Health in Students. Uncorrected visual acuity and cycloplegic refraction were tested. Multivariate logistic regression analysis was performed to explore myopia-related factors. Results: A total of 990 questionnaires were distributed, and 882 valid questionnaires were recovered, with an effective rate of 89.09%. The prevalence rate of myopia was 78.23% ( 690 cases ). Multivariate logistic regression analysis showed that females ( OR=1.703, 95%CI: 1.173-2.474 ) , middle school students ( OR:5.597-11.949, 95%CI: 3.573-28.349 ) , both parents＇myopia ( OR=2.445, 95%CI: 1.597-3.742 ) , video display terminal time over 3 hours per day ( OR=2.026, 95%CI: 1.235-3.325 ) were risk factors for myopia; outdoor activity time over 2 hours per day ( OR: 0.493-0.510, 95%CI: 0.273-0.943 ) was a protective factor for myopia. Conclusion The prevalence of myopia among primary and secondary school students in Suzhou is 78.23%. Gender, grade, parents＇ myopia history, outdoor activity time and video display terminal time are influencing factors for myopia.

Amorphous solid dispersion (ASD) is one of the most effective formulation approaches to enhance the water solubility and oral bioavailability of poorly water-soluble drugs. However, maintenance of physical stability of amorphous drug is one of the main challenges in the development of ASD. Crystallization is a process of nucleation and crystal growth. The nucleation is the key factor that influences the physical stability of the ASD. However, a theoretical framework to describe the way to inhibit the nucleation of amorphous drug is not yet available. We reviewed the methods and theories of nucleation for amorphous drug. Meanwhile, we also summarized the research progress on the mechanism of additives influence on nucleation and environmental factors on nucleation. This review aims to enhance the better understanding mechanism of nucleation of amorphous drug and controlling over the crystal nucleation during the ASD formulation development.

OBJECTIVETo investigate the changes in the expression of aquaporin 1 (AQP-1) in edematous small intestinal tissues of rats after severe burn and the effect of early enteral feeding on its expression.

METHODSNinety normal adult Wistar rats were randomly divided into normal control group (n=6), burn model group (n=42, with 30% TBSA III degrees) and early feeding group (n=42). Dry weight method, ELSIA and immunohistochemistry were used to observe and detect the water content and expression of AQP-1 in the intestinal tissue at 1, 4, 8, 12, 24, 48, and 72 h after the burns.

RESULTSIn the burn model group, the water content in the intestinal tissue increased at 4 h after the injury, reaching the peak level at 48 h; AQP-1 expression decreased at 8 h after severe burn and reached the lowest level at 48 h. AQP-1 expression level showed a significant inverse correlation to the water content (P<0.01). Compared with the burn model group, the rats in the early feeding group showed increased AQP-l expression and lessened edema in the small intestines, also demonstrating an inverse correlation between water content and AQP-l expression (P<0.01).

CONCLUSIONIntestinal AQP-1 expression gradually decreased and edema worsened in rats early after severe burn, reaching the lowest or the peak levels 48 h after the injury with an inverse correlation between them. Early enteral feeding can increase the expression of AQP-l in the small intestine to ameliorate the intestinal edema in rats with severe burn injury.

Animals ; Aquaporin 1 ; metabolism ; Burns ; diet therapy ; metabolism ; Edema ; metabolism ; Enteral Nutrition ; Female ; Intestine, Small ; metabolism ; pathology ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Time Factors

OBJECTIVETo investigate the influence of sea water immersion on inflammation and healing of the wounds in scalded rats.

METHODSOne hundred and forty-four male Wistar rats with 10% TBSA superficial partial-thickness scald were randomly divided into A (n=72, with scald) and B (n=72, with seawater immersion for 4hrs immediately after scald) groups. The serum contents of K+, Na+, Cl- were determined at 0 post-scald hour (PSH), 6PSH, 12PSH and 24 PSH with electrocyte analysis apparatus, and the changes in serum interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha) levels were determined at 0 PSH, 6PSH and 12 PSH with enzyme-linked immunosorbent assay (ELISA). The histopathological changes in the rats of the two groups were observed, and wound healing time was respectively calculated.

RESULTSThe serum contents of K+, Na+, Cl- in B group were obviously higher than those in A group. And the serum content of TNF-alpha and IL-6 in B group at 6 PSH [(140 +/- 22) ng/L, (160 +/- 41) ng/L] were significantly higher than those before scald [(29 +/- 15) ng/L, (62 +/- 17)] ng/L and in A group [(120 +/- 12) ng/L, (124 +/- 22) ng/L, ( P < 0.05)]. Compared with A group, re-epithelization of the wound differentiation in all layers of epidermis were delayed in B group, with more severe wound swelling, exudation, and topical inflammatory response. The wound healing time in B group was (16.3 +/- 1.6) d, which was obviously longer than that in A group [(14.1 +/- 1.8) d, P < 0.05)].

CONCLUSIONSea water immersion combined with scald injury can aggravate the inflammatory response of the wound and delay the wound healing process.

Animals ; Burns ; pathology ; Disease Models, Animal ; Inflammation ; Interleukin-6 ; analysis ; Male ; Rats ; Rats, Wistar ; Seawater ; adverse effects ; Tumor Necrosis Factor-alpha ; analysis ; Wound Healing

Female ; Humans ; Lymphoma, T-Cell ; diagnosis ; Middle Aged ; Multiple Myeloma ; diagnosis

Carotid Artery, Internal/surgery* ; Carotid Stenosis/surgery* ; Endarterectomy, Carotid ; Humans ; Treatment Outcome

BACKGROUNDFew studies have investigated perioperative major adverse cardiac events (MACEs) in elderly Chinese patients with coronary heart disease (CHD) undergoing noncardiac surgery. This study examined the incidence and risk factors for perioperative MACE in elderly patients who underwent noncardiac surgery, and established a risk stratification system.

METHODSThis retrospective observational clinical study included 482 patients aged ≥60 years with CHD who underwent elective major noncardiac surgery at the Peking Union Medical College Hospital. The primary outcome was MACE within 30 days after surgery. Risk factors were evaluated using multivariate Logistic regression analysis.

RESULTSPerioperative MACE occurred in 61(12.66%) of the study patients. Five independent risk factors for perioperative MACE were identified: history of heart failure, preoperative arrhythmia, preoperative diastolic blood pressure ≤75 mmHg, American Society of Anesthesiologists grade 3 or higher, and intraoperative blood transfusion. The area under the receiver operating characteristic curve for the risk-index score was 0.710±0.037. Analysis of the risk stratification system showed that the incidence of perioperative MACE increased significantly with increasing levels of risk.

CONCLUSIONSElderly Chinese patients with CHD who undergo noncardiac surgery have a high risk of perioperative MACE. Five independent risk factors for perioperative MACE were identified. Our risk stratification system may be useful for assessing perioperative cardiac risk in elderly patients undergoing noncardiac surgery.

Aged ; Aged, 80 and over ; Coronary Disease ; complications ; Elective Surgical Procedures ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Postoperative Complications ; Retrospective Studies ; Risk Assessment

OBJECTIVETo evaluate the feasibility and usability of multi-slice computed tomography (MSCT) in congenital inner ear malformations.

METHODSFourty-four patients with sensorineural hearing loss (SNHL) were examined by a Somatom Sensation 16 (siemens, Germany) CT scanner with following parameters: 120 kV, 100 mAs, 0.75 mm collimation, 1 mm reconstruction increment, a pitch factor of 1 and a field of view of 100 mm. The axial images of interested ears were reconstructed with 0.1 mm reconstruction increment, and a field of view of 50 mm. The 3D reconstructions were done with volume rendering technique (VRT) on the workstation (3D Virtuoso and Wizard,siemens).

RESULTSTwenty-five patients were normal and 19 patients (36 ears) were congenital inner ear malformations among 44 patients scanned with MSCT. Of the malformations, all the axial, MPR and VRT images can display the site and degree in 33 ears. VRT images were superior to the axial images in displaying the malformations in 3 ears with the small lateral semicircular canal malformations. The malformations were Michel deformity (1 ear), common cavity deformity (3 ears), incomplete partition I (3 ears), incomplete partition II (Mondini deformity, 5 ears), vestibular and semicircular canal malformations( 14 ears), vestibular aqueduct dilate( 16 ears, of which 6 ears accompanied by other malformations), the internal auditory canal malformation(8 ears, all accompanied by other malformations).

CONCLUSIONMSCT allows a comprehensively assessing various congenital ear malformations through high quality MPR and VRT reconstructions. VRT images can display the site and degree of the malformations three-dimensionally and intuitionisticly. It is very useful to the cochlear implantation.

Adolescent ; Adult ; Case-Control Studies ; Child ; Child, Preschool ; Congenital Abnormalities ; diagnostic imaging ; Ear, Inner ; abnormalities ; diagnostic imaging ; Female ; Humans ; Male ; Tomography, Spiral Computed ; Young Adult

OBJECTIVETo investigate the changes in the myocardial expression of aquaporin-1 (AQP1) protein and its association with myocardial edema in rats with severe burns.

METHODSForty-eight healthy adult Wistar rats were randomly divided into normal control group (n=6) and burn injury group with third degree burn of 30% total body surface area, and the latter group was further divided into 2, 4, 8, 12, 24, 48 and 72 h groups. The changes of myocardial water content were investigated by dry-wet weight methods. Enzyme-linked immunosorbent assay was used to detect the changes in AQP1 expression at different time points after sever burns.

RESULTSThe myocardial water content and AQP1 expression increased significantly 2 h after the burn injury, reaching the peak levels at 12 h and remaining higher than the normal level at 48 h. A significant positive correlation was found between myocardial water content and AQP1 expression in the rats (r=0.868, P<0.01).

CONCLUSIONThe severity of myocardial edema after severe burn is correlated to the expression level of AQPl protein, suggesting the important role of AQPl protein in pathological progression of myocardial edema.

Animals ; Aquaporin 1 ; genetics ; metabolism ; Burns ; metabolism ; pathology ; Edema ; metabolism ; Female ; Male ; Myocardium ; metabolism ; pathology ; Random Allocation ; Rats ; Rats, Wistar