Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), is a common hepatic manifestation of metabolic syndrome. However, there are no effective therapy to treat this devastating disease. Accumulating evidence suggests that the generation of elastin-derived peptides (EDPs) and the inhibition of adiponectin receptors (AdipoR)1/2 plays essential roles in hepatic lipid metabolism and liver fibrosis. We recently reported that the AdipoR1/2 dual agonist JT003 significantly degraded the extracellular matrix (ECM) and ameliorated liver fibrosis. However, the degradation of the ECM lead to the generation of EDPs, which could further alter liver homeostasis negatively. Thus, in this study, we successfully combined AdipoR1/2 agonist JT003 with V14, which acted as an inhibitor of EDPs-EBP interaction to overcome the defect of ECM degradation. We found that combination of JT003 and V14 possessed excellent synergistic benefits on ameliorating NASH and liver fibrosis than either alone since they compensate the shortage of each other. These effects are induced by the enhancement of the mitochondrial antioxidant capacity, mitophagy, and mitochondrial biogenesis via AMPK pathway. Furthermore, specific suppression of AMPK could block the effects of the combination of JT003 and V14 on reduced oxidative stress, increased mitophagy and mitochondrial biogenesis. These positive results suggested that this administration of combination of AdipoR1/2 dual agonist and inhibitor of EDPs-EBP interaction can be recommended alternatively for an effective and promising therapeutic strategy for the treatment of NAFLD and NASH related fibrosis.

Currently, there is still no effective curative treatment for the development of late-stage liver fibrosis. Here, we have illustrated that TB001, a dual glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) agonist with higher affinity towards GCGR, could retard the progression of liver fibrosis in various rodent models, with remarkable potency, selectivity, extended half-life and low toxicity. Four types of liver fibrosis animal models which were induced by CCl₄, α-naphthyl-isothiocyanate (ANIT), bile duct ligation (BDL) and Schistosoma japonicum were used in our study. We found that TB001 treatment dose-dependently significantly attenuated liver injury and collagen accumulation in these animal models. In addition to decreased levels of extracellular matrix (ECM) accumulation during hepatic injury, activation of hepatic stellate cells was also inhibited via suppression of TGF-β expression as well as downstream Smad signaling pathways particularly in CCl₄-and S. japonicum-induced liver fibrosis. Moreover, TB001 attenuated liver fibrosis through blocking downstream activation of pro-inflammatory nuclear factor kappa B/NF-kappa-B inhibitor alpha (NFκB/IKBα) pathways as well as c-Jun N-terminal kinase (JNK)-dependent induction of hepatocyte apoptosis. Furthermore, GLP-1R and/or GCGR knock-down results represented GCGR played an important role in ameliorating CCl₄-induced hepatic fibrosis. Therefore, TB001 can be used as a promising therapeutic candidate for the treatment of multiple causes of hepatic fibrosis demonstrated by our extensive pre-clinical evaluation of TB001.

The antimicrobial peptide APKGVQGPNG (named YD), a natural peptide originating from Bacillus amyloliquefaciens CBSYD1, exhibited excellent antibacterial and antioxidant properties in vitro. These characteristics are closely related to inflammatory responses which is the central trigger for liver fibrosis. However, the therapeutic effects of YD against hepatic fibrosis and the underlying mechanisms are rarely studied. In this study, we show that YD improved liver function and inhibited the progression of liver fibrosis by measuring the serum transaminase activity and the expression of α-smooth muscle actin and collagen I in carbon tetrachloride-induced mice. Then we found that YD inhibited the level of miR-155, which plays an important role in inflammation and liver fibrosis. Bioinformatics analysis and luciferase reporter assay indicate that Casp12 is a new target of miR-155. We demonstrate that YD significantly decreases the contents of inflammatory cytokines and suppresses the NF-κB signaling pathway. Further studies show that transfection of the miR-155 mimic in RAW264.7 cells partially reversed the YD-mediated CASP12 upregulation, the downregulated levels of inflammatory cytokines, and the inactivation of the NF-κB pathways. Collectively, our study indicates that YD reduces inflammation through the miR-155–Casp12–NF-κB axis during liver fibrosis and provides a promising therapeutic candidate for hepatic fibrosis.

Objective To evaluate the application value of automatic tube current modulation (ATCM) in low dose chest scaning with 64-slices spiral dual-resource CT. Methods Randomly selected healthy people to participate in our hospital from March 2014 to July 2014 in subjects with chest CT examination were 200, 100,received low dose spiral CT examination,as the A group;the other 100 underwent routine CT plain scan,as the B group,All CT images were analyzed by two radiologists with double blind method.Image quality scores (IQS)of lung apex,middle lung and lower lung were made,the image standard deviation(SD)was measured,and the CTDIvol was also recorded,and the statistical analysis was performed. Results SD values in lung apex,middle and lower lungs was (34.34±2.17),(30.63±0.74),(30.74±1.21)in group A,and (36.82±2.51)、(34.15±1.98),(31.69±1.93 )in group B,as well as the corresponding IQS of these three sites were(1.83±0.36),(1.59±0.38),(1.64±0.34)in group A,and(2.31±0.47),(1.68±0.42),(1.73±0.48)in group B,respectively. SD value and IQS of group A were lower than those of group B in lung apex(P<0.05). Conclu-sion The application of ATCM in low dose chest CT scanning plus noise suppression can provide more homogeneous images with better image quality.

Objective To analyze the effect of bifrontal decompressive craniectomy on patients with refractory diffusing of brain swelling after severe traumatic brain injury.Methods The clinical data of 68 patients with refractory diffusing of brain swelling after severe traumatic brain injury were analyzed retrospectively.Thirty-five patients were performed with bifrontal decompressive craniectomy as observed group,continued intracranial pressure monitoring after surgery.Thirty-three patients were treated conservatively to reduce intracranial pressure as control group,continued intracranial pressure monitoring.The Glasgow outcome scale after discharge 6 months were assessed.The efficacy,the incidence of complications were observed in observed group.Results The admission intracranial pressure in observed group was significantly higher than that after surgery [(35.9 ±6.9) mmHg (1 mmHg =0.133 kPa) vs.(17.5 ±5.2) mmHg,P ＜0.05].The admission intracranial pressure in control group was (34.2 ± 8.6) mmHg,after admission 10.5 h was (32.0 ±4.8) mmHg (P ＜0.05),difference was no statistically significant (P＞ 0.05).The intracranial pressure after admission 10.5 h in control group was significantly higher than that in observed group after surgery (P ＜0.05).Two cases of subdural effusion,1 case of postoperative hydrocephalus in observed group.The better prognosis rate in observed group was significantly higher than that in control group [45.7％ (16/35) vs.18.2％ (6/33),P ＜ 0.05].Conclusions Bifrontal decompressive craniectomy is a suitable measure to decrease the intracranial pressure in the patients with refractory diffusing of brain swelling.If carried out early,it could provide better outcome for these patients.

Objective To investigate the CT features and the diagnostic value in invasive mole. Methods Eleven cases (age, 30 to 53 years, mean 40 years)with invasive mole proved by operation and pathology were studied, including 3 cases during peri menopausal period of eight months, ten months and twelve months respectively. All cases were scanned by CT and enhanced study was done. Results All cases showed enlargement of uterus of varying degrees. On CT, the density of uterine cavity was similar to that of water, intermingled with spotty patchy and hazzy circular isodense shadows. High density stripe like bleeding foci were found in 3 cases.The outline of uterine cavity was locally disrupted in all case and the muscle layer was thickened in 3 cases. On enhanced CT scan, the lesions in the uterine cavity appeared markedly hyperdense, just like “the crater” and the “mole sign” .The muscle layers at the site of disruption showed inhomogeneous enhancement after contrast injection. Conclusion The CT features of invasive mole are characteristic, with important diagnostic value, especially for those during peri menopausal period.