Activation of the STING-IRF3 pathway involved in psoriasis with diabetes mellitus.

Psoriasis and type 2 diabetes mellitus (T2DM) share similar inflammatory pathways in their pathogenesis. The stimulator of interferon genes (STING)-interferon regulatory factor 3 (IRF3) pathway has recently been shown to play an important role in immune and metabolic diseases. In this study, we investigated the activation of the STING-IRF3 pathway in human immortalized keratinocytes (HaCaT) cells treated with palmitic acid (PA) and imiquimod (IMQ). Additionally, we detected the STING-IRF3 pathway in diabetic mice with imiquimod (IMQ)-induced psoriasis and assessed the potential of STING inhibitor C-176. Furthermore, skin samples from patients with psoriasis and diabetes were collected for immunohistochemical analysis. The results indicated that the STING-IRF3 pathway was activated in HaCaT cells. Moreover, the STING pathway was also found to be induced in the skin tissue of diabetic mice with psoriasis; the inflammatory responses were ameliorated by treatment with C-176. In the skin tissue samples of patients with psoriasis and diabetes, immunohistochemistry showed that the expression levels of STING and phosphorylated IRF3 were also significantly increased. Thus, we conclude that the STING-IRF3 pathway is involved in the inflammatory response in the manifestation of psoriasis with T2DM. Inhibition of the activation of the STING pathway can ameliorate the development of psoriasis in diabetes and could be targeted for the development of therapeutic agents for these conditions.

Vascularization of pancreatic decellularized scaffold with endothelial progenitor cells.

Vascularization remains a large obstacle for creating a functional pancreas-tissue equivalent for transplantation. In this study, a pre-vascularized pancreatic decellularized scaffold was prepared through endothelializing with endothelial progenitor cells (EPCs) in a bioreactor, and the ability to regenerate new blood vessels was detected in vivo. Initially, pancreases of Sprague-Dawley (SD) rats were perfused with 1% Triton X-100 and 0.1% ammonium hydroxide to remove the cellular components while the intact vascular network was preserved. Then, the decellularized scaffold was reseed with EPCs, which were primarily characterized by dual staining for dil-labeled acetylated low-density lipoprotein (Dil-acLDL) and fluorescein isothiocyanate labeled ulex europaeus agglutinin 1 (FITC-UEA-1), to reconstruct the vascular network. Thus, a scaffold covered with EPCs in the vessel structure was created. After that, the scaffold was transplanted into the rat in vivo to observe the anastomosis with the host vascular network. The results showed that EPCs can be located around the blood vessel wall, and re-endothelialized scaffold connected with the host through new blood vessel formation earlier than the control group (p < 0.05). These findings all indicated that the pancreatic decellularized scaffold endothelialized with EPCs may be further applied to solve the problem of blood supply and support the function of insulin-secreting cells after in vivo transplantation.

Effect of lit-moxa stimulation of Guanyuan (CV 4) acupoint on levels of lactic acid and superoxide dismutase in skeletal muscle of rats.

OBJECTIVE: To observe the effect of lit-moxa stimu- lating acupoint Guanyuan (CV 4) on lactic acid and super-oxide dismutase (SOD) in skeletal muscle after exercise exhaustion. METHODS: Twenty-eight adult male Sprague-Dawley rats were randomly divided into normal control group, exhausted control group, exercise group and moxibustion group using exercise training and mild heating with lit-moxa stick as treatment methods. The exhausted control group, moxibustion group and exercise group received an exhaustive swimming after 20 days of intervention. Swimming exhausted times were recorded. Lactic acid and SOD concentration in soleus muscle were detected and compared between every two groups. RESULTS: The swimming exhausted times of the moxibustion group and the exercise group were significantly increased compare to the exhausted control group (P < 0.05). The lactic acid of the exhausted control group was significantly increased comparing with the normal control group (P < 0.05), and the lactic acid of the moxibustion group and the exercise group were significantly lower than that of the exhausted control group (P < 0.05). The SOD level of the exhausted control group was significantly decreased comparing with the normal control group (P < 0.05), and the SOD level of the moxibustion group and the exercise group were significantly higher than that of the exhausted control group (both, P < 0.05). There was no statistical difference between the moxibustion group and the exercise group. CONCLUSION: With lit moxa stick, heat stimulating acupoint of Guanyuan (CV 4) decreased the levels of lactic acid and SOD in rat's skeletal muscle.

Improved outcome of haploidentical transplantation in severe aplastic anemia using reduced-intensity fludarabine-based conditioning.

Significant improvements in hematopoietic stem cell transplantation (HSCT) with haploidentical family donors (HFD) have confirmed its therapeutic role in severe aplastic anemia (SAA) and led to the evolution of treatment algorithms. However, the optimal conditioning regimen for HFD-HSCT remains undefined, especially the dosage of cyclophosphamide (Cy). A total of 77 patients with SAA from two research centers, who received HFD-HSCT with reduced-intensity fludarabine + cyclophosphamide + thymoglobulin ± busulfan conditioning regimen plus third-party cells infusion were included in this study, of which 67 pairs had 4-5 loci mismatched. We were particularly interested in whether the dosage of Cy significantly impacted graft failure (GF) and overall survival (OS). All patients showed sustained hematopoietic engraftment without any increase in severe aGVHD and transplantation-related mortality (TRM). The incidences of grade II-IV aGVHD, grade III-IV aGVHD and extensive cGVHD were 18%, 10% and 7%, respectively. The probabilities of 1-year and 5-year OS were 93.1% and 87.9%, respectively. Furthermore, patient age <15 years, MNC cells >8×108/kg and donor age <45 years were associated with better survival (P=0.043, P=0.023, and P=0.037, respectively) and engraftment (P=0.019, P=0.008, and P=0.001, respectively). Our findings indicated that SAA patients lack MSD benefited the most if HFD-HSCT was performed with reduced-intensity fludarabine-based conditioning regimen. Improved outcomes with HFD-HSCT may lead to a salvaged therapy and an expanded direct role for SAA in the future.

CT perfusion imaging of the stomach: a quantitative analysis according to different degrees of adenocarcinoma cell differentiation.

OBJECTIVES: To evaluate clinical usefulness of computed tomography perfusion imaging (CTPI) in gastric cancer. MATERIALS AND METHODS: Twenty subjects without gastric diseases (control group) and fifty patients with gastric cancer were studied prospectively using CTPI examinations. Four perfusion parameter values, i.e., blood flow (BF), blood volume (BV), mean transit time, and permeability surface (PS), were calculated. The gastric cancer group was divided into three groups: well differentiated, moderately differentiated, and poorly differentiated gastric adenocarcinoma. RESULTS: Comparing the three groups, differences between the well-differentiated group and the moderately differentiated group or the poorly differentiated group were all statistically significant for BF, BV, and PS. CONCLUSION: The BF, BV, and PS values could serve as indicators of the degree of malignancy of gastric cancer.

Porcine model of congenital heart defect with decreased pulmonary blood flow.

A porcine model was produced to study the pathophysiology of congenital heart defect (CHD) with decreased pulmonary blood flow. Twenty piglets (1-2 months) were randomly divided as mild to moderate stenosis/T(1) group (n = 7) in which artificial atrial septal defect (ASD) with pulmonary artery banding generated a systolic pressure gradient of 20-30 mmHg; severe stenosis/T group (n = 7) group with a systolic pressure gradient of ≥30-50 mmHg; and controls/C group (n = 6) underwent sham surgery. At 1 month postoperatively, 64-slice computed tomography (CT) was performed. At 2 months, left-chest surgery was performed to measure ASD diameter, arterial blood gas, hemoglobin, and Trans-PABP. Our data show successful establishment of porcine CHD model. ASDs in T(1)/T(2) groups were 8.0 ± 0.5/8.9 ± 1.4 mm, respectively. Trans-PABP showed that the pressure increase in T(2) was higher (P < 0.01) than in T(1) group. Arterial blood PaO(2) and SaO(2) of T(1/)T(2) groups were significantly lower than controls. AoD was significantly lower in T(1) than in C group. Balloon dilation was significantly lower than AoD in T(1)/T(2) groups. Besides, one animal in T(1), two animals in T(2) ,and one animal in C group died. We conclude that ASD with pulmonary artery banding is a successful intervention to establish such a model, and our findings may influence the treatment of patients with similar heart disease.

Computational study of imidazole derivative as high energetic materials.

Density functional theory (DFT) calculations were performed for a series of imidazole derivatives. B3LYP and B3P86 functionals with 6-31G** basis set were used. Heats of formation (HOFs) were predicted through designed isodesmic reactions. Calculated results show that the HOFs relate to the number and the position of nitro groups. The HOFs increase with the augment of the number of the NO(2) group for the direct imidazole derivatives and decrease with the augment of the number of the NO(2) group for 1-picrylimidazole derivatives. Thermal stabilities were evaluated via bond dissociation energies (BDEs). The result shows that the increase of nitro group number on imidazole ring reduces the stability of the molecule. Further, the correlation was developed between impact sensitivity h(50) and the ratio (BDE/E) of the weakest bond BDE to the total energy E. The detonation performance data were also calculated.

A study on rural-urban differences in neonatal mortality rate in China, 1996-2006.

OBJECTIVE: This study examined the differences in neonatal mortality rates between urban and rural areas in China. METHODS AND RESULTS: Data were taken from a database collected by the Chinese surveillance network for mortality of children under 5 years of age. The risk ratio of neonatal mortality for rural versus urban areas was between 2.2 and 2.7 for 1996-2006 and it declined to 2.0 in 2005-6. Pneumonia, birth asphyxia and preterm birth or low birth weight were the major contributors to the urban-rural differences in neonatal mortality, together with a relatively high proportion of home delivery and a relatively lower proportion of hospital treatment in rural areas. CONCLUSION: The urban-rural differences reflect the gap between the developed and the underdeveloped regions in China at that period. The neonatal mortality rate in China's rural areas could decrease further if continuous efforts are successful to increase the rates of hospital delivery in rural areas.