Autism Spectrum Disorders (ASDs) are reported as a group of neurodevelopmental disorders. The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes, but the underlying mechanisms are not fully understood. Here, we report that deletion of Trio, a high-susceptibility gene of ASDs, causes a postnatal dentate gyrus (DG) hypoplasia with a zigzagged suprapyramidal blade, and the Trio-deficient mice display autism-like behaviors. The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells (GCs), which further results in a migration deficit of neural progenitors. Furthermore, we reveal that Trio plays different roles in various excitatory neural cells by spatial transcriptomic sequencing, especially the role of regulating the migration of postmitotic GCs. In summary, our findings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.
Animals ; Dentate Gyrus/metabolism* ; Mice ; Morphogenesis/physiology* ; Neurons/pathology* ; Cell Movement ; Mice, Inbred C57BL ; Autism Spectrum Disorder/pathology* ; Mice, Knockout ; Neural Stem Cells ; Male ; Neurogenesis ; Autistic Disorder/genetics*

Objective:To investigate the in vitro inhibitory effect of methylene blue mediated photodynamic therapy (PDT) combined with berberine on Porphyromonas gingivalis (P.g). Methods:P.g was cultured until the middle to late log phase, and methylene blue was added to P.g suspension at different mass concentrations for 5 min, and a laser (wavelength 660 nm, power 140 mW/cm 2) was irradiated for 2 min to find the optimal concentration of methylene blue combined with the laser for in vitro inhibition of P.g. The effect of methylene blue mediated PDT on the in vitro inhibition of P.g and the effect of berberine on the growth curve of P.g were observed. The inhibitory effect of methylene blue mediated PDT and berberine on P.g was investigated by successive combined applications. The effect of methylene blue mediated PDT on P.g morphology was observed by scanning electron microscopy. The absorption peaks of each component were measured by ultraviolet spectrophotometer. Results:The best inhibition was achieved at a methylene blue mass concentration of 24.414 1 μg/ml under 660 nm laser excitation. The differences were statistically significant in both the methylene blue and PDT groups compared with the control group (all P<0.001). 0.05 mg/ml berberine had an inhibitory effect on the planktonic bacteria of P.g. After P.g was treated with methylene blue mediated PDT, the bacterial cell walls were crumpled into clusters. Compared with the control group, the number of colonies was reduced in the 0.05 mg/ml berberine group, and the difference was statistically significant ( P<0.01). The difference between the 0.05 mg/ml berberine + light group and the control group was not statistically significant ( P>0.05). When PDT was combined with berberine, there was a synergistic inhibitory effect on P.g. PDT followed by berberine shows a better inhibitory effect on bacteria, and the differences were statistically significant (all P<0.01). After the berberine treatment, the bacterial surface became smooth, and the length of the bacterial body increased compared with the control group. Conclusions:Methylene blue mediated PDT has an inhibitory effect on P.g. When combined with berberine, it has a synergistic inhibitory effect on P.g., and the inhibition effect is better when PDT is applied first and then berberine is applied in combination.

Objective: To investigate the effect of perioperative fluid therapy on early postoperative pulmonary complication (PPC) after orthotopic liver transplantation (OLT). Methods: The clinical data of 132 patients who underwent OLT in the First Affiliated Hospital of Xi′an Jiaotong University from April 2016 to December 2017 were analyzed retrospectively. These patients included 96 males and 36 females, aged (47.3±9.6) years (range: 24-69 years). Based on the clinical manifestations, laboratory and imaging findings of patients in ICU and PPC occurrence within 7 days after OLT surgery, the patients were divided into 2 groups: non-PPC group and PPC group. Univariate and multivariate logistic regression analyses were used to evaluate the association between perioperative variables and PPC. The Kaplan-Meier method was used to estimate cumulative survival of recipients with or without PPC within 2-years. Results: During the follow-up, 11 patients (8.3%) died and 72 patients (54.5%) developed PPC after operation. There were 34 cases, 6 cases, 3 cases, 4 cases, 15 cases, 6 cases and 4 cases of only pleural effusion, only pulmonary edema, only pneumonia, pleural effusion with pneumonia, pleural effusion with pulmonary edema, pleural effusion with atelectasis, and pleural effusion with pneumonia and pneumonia in PPC, respectively. Univariate analysis showed that the preoperative factors (model for end-stage liver disease score), the intra-operative factors (duration of surgery, total infusion volume, total blood products) and the postoperative cumulative fluid balance within the first 24 h, 48 h, and 72 h were the prognosis factors of PPC (P<0.05). At least two out of the first three postoperative days with a fluid balance of ≤-500 ml was a protective factor. Using multivariate analysis by Logistic regression, only the red blood units >10 U (OR=3.55, 95% CI: 1.35-9.26, P=0.010) and the cumulative fluid intake >12 L (OR=2.98, 95% CI: 1.14-7.80, P=0.026) within the first 72 h after operation were independent prognosis factors of PPC after OLT. Kaplan-Meier analysis showed that the cumulative survival rate was lower in PPC group than that in non-PPC group (χ²=6.590, P=0.01). Conclusion Massive red blood cell transfusion and the cumulative fluid volume >12 L during perioperative 72 hours are independent prognosis factors of PPC after OLT.