Objective:To investigate the role and underlying mechanism of parthanatos death in neonatal SD rats with bilirubin encephalopathy(BE).Methods:Eighty 3-day-old neonatal SD rats were selected and randomly divided into control group and BE group.The BE model was established by intraperitoneal injection of bilirubin solution,and the pathological changes in the hippocampus were observed by hematoxylin-eosin(HE)staining and Nissl staining.The protein expressions of the phosphorylation of the core histone protein H2AX(termed gamma H2AX),poly ADP-ribose polymerasw-1(PARP-1)and apoptosis-inducing factor(AIF)in hippocampus were detected by Western blot.Immuno-fluorescence staining was used to detect the expression and distribution of AIF in hippocampus.Results:Compared with the control group,neonatal SD rats developed jaundice 12 hours after bilirubin injection,accompanied by slow weight gain.HE staining and Nissl staining showed that the hippocampus in BE group were damaged and the content of Nissl bodies was decreased.Western blot results showed that the expression of γ-H2AX protein in hippocampus began to increase at 72 h after modeling(P＜0.05),and the levels of PARP-1 and AIF protein in hippocampus increased signif-icantly at 72 h after modeling(P＜0.05).Immunofluorescence staining showed increased AIF expression and nuclear translocation.Conclusion:Intraperitoneal injection of bilirubin can induce DNA damage in hippocampal neurons of neonatal SD rats and activate the PARP-1/AIF pathway to cause parthanatos death of hippocampal neurons.

Objective:To investigate the role and underlying mechanism of parthanatos death in neonatal SD rats with bilirubin encephalopathy(BE).Methods:Eighty 3-day-old neonatal SD rats were selected and randomly divided into control group and BE group.The BE model was established by intraperitoneal injection of bilirubin solution,and the pathological changes in the hippocampus were observed by hematoxylin-eosin(HE)staining and Nissl staining.The protein expressions of the phosphorylation of the core histone protein H2AX(termed gamma H2AX),poly ADP-ribose polymerasw-1(PARP-1)and apoptosis-inducing factor(AIF)in hippocampus were detected by Western blot.Immuno-fluorescence staining was used to detect the expression and distribution of AIF in hippocampus.Results:Compared with the control group,neonatal SD rats developed jaundice 12 hours after bilirubin injection,accompanied by slow weight gain.HE staining and Nissl staining showed that the hippocampus in BE group were damaged and the content of Nissl bodies was decreased.Western blot results showed that the expression of γ-H2AX protein in hippocampus began to increase at 72 h after modeling(P＜0.05),and the levels of PARP-1 and AIF protein in hippocampus increased signif-icantly at 72 h after modeling(P＜0.05).Immunofluorescence staining showed increased AIF expression and nuclear translocation.Conclusion:Intraperitoneal injection of bilirubin can induce DNA damage in hippocampal neurons of neonatal SD rats and activate the PARP-1/AIF pathway to cause parthanatos death of hippocampal neurons.

Objective:To observe the effect of astragaloside Ⅳ on lysophosphatidic acid(LPA)- induced neurite retraction of N1E-115 cells and its potential mechanism.Methods:N1E-115 cells were divided into blank group, model group, the low, medium and high dose groups of astragaloside Ⅳ. The blank group and model group was not intervened by astragaloside; while the low, medium and high dose groups were treated with 20,40 and 80 μg/ml astragaloside Ⅳ for 24 h. Each group was cultured with serum-free medium for 12 h. The model group and astragaloside Ⅳ groups were intervened by 40 μmol/L LPA for 10 min. Each group was observed and photographed with the inverted microscope, and the number of neurites in N1E-115 cells was counted by Image J software. The fluorescence expression of recombinant ras homolog gene family member A (RhoA), rho associated coiledcoil protein kinase 2 (ROCK2), phospho-rho associated coiledcoil protein kinase 2 (p-ROCK2) and phospho-myosin light chain 2 (p-MLC2) proteins was detected by immunohistochemistry. Real-time fluorescent quantitative polymerase chain reaction was used to detect the mRNA expression levels of RhoA and ROCK2 ; the protein expression levels of RhoA, ROCK2, p-MLC2 and myosin light chain 2 (MLC2) were detected by Western blotting.Results:Compared with 20 μg/ml astragaloside Ⅳ group, the inhibition rate of neurite retraction in 40 and 80 μg/ml astragalosideⅣ groups increased ( P<0.05). Compared with model group, the average fluorescence intensity of RhoA, p-ROCK2, p-MLC2 in 20, 40, 80 μg/ml astragaloside Ⅳ groups and the ROCK2 average fluorescence intensity in 40 μg/ml astragaloside Ⅳ group were decreased ( P<0.05, P<0.01); the expression of RhoA mRNA (0.89±0.09, 0.41±0.01, 0.09±0.03 vs. 1.50±0.01) and ROCK2 mRNA (0.89±0.09, 0.14±0.01, 0.20±0.01 vs. 1.62±0.17) decreased in 20, 40, 80 μg/ml astragaloside Ⅳ groups ( P<0.05, P<0.01); the ROCK2 protein (0.75±0.06, 0.57±0.02, 0.66±0.01 vs. 1.08±0.02), p-MLC2 protein (1.72±0.03, 1.40±0.04, 1.29±0.03 vs. 2.19±0.11), MLC2 protein (1.13±0.02, 0.68±0.03, 0.75±0.03 vs. 1.60±0.03) in 20, 40, 80 μg/ml astragaloside Ⅳ groups and the RhoA protein (0.35±0.01, 0.40±0.03 vs. 0.57±0.08) in 20, 40 μg/ml astragaloside Ⅳ groups were decreased ( P<0.05, P<0.01). Conclusion:Astragaloside Ⅳ can prevent LPA-induced neurite retraction and promote damaged nerve regeneration. The mechanism may down-regulae the protein expression levels of RhoA, ROCK2, p-ROCK2, p-MLC2 and MLC2 in RhoA-ROCK2 signaling pathway, and inhibite nerve growth cone collapse.

Background::Endoscopic ultrasound (EUS)-guided transmural drainage for pancreatic fluid collections (PFCs) has become the first-line treatment with quicker recovery and more minor injury compared with surgery and percutaneous drainage. The efficacy of stents implantation and drainage for different PFCs remains controversial, especially lumen-apposing metal stents (LAMS). This study aimed to compare the efficacy and safety of LAMS drainage for pancreatic pseudocysts (PPC) and walled-off necrosis (WON).Methods::A meta-analysis was performed for LAMS drainage for WON and PPC by systematically searching PubMed, Cochrane, and Embase databases from January 2010 to January 2020. From 2017 to 2019, 12 patients who were treated with LAMS drainage for PFCs in our medical center were also reviewed and included in this study.Results::Combining 11 copies of documents with the data from our medical center, a total of 585 patients with PFCs were enrolled in this meta-analysis, including 343 patients with WON and 242 with PPC. The technical success rate in WON is not significantly different from that of PPC ( P = 0.08 > 0.05). The clinical success of LAMS placement was achieved in 99% vs 89% in PPC and WON, respectively (RR = 0.92, 95% CI: 0.86-0.98, P = 0.01 < 0.05). The further intervention of direct endoscopic necrosectomy was required by 60% of patients in WON group. There was no significant difference in the incidence of adverse events, including infection, bleeding, stent migration and stent occlusion, after LAMS placement between WON and PPC. Conclusions::Endoscopic ultrasound-guided LAMS for PFCs are feasible, effective with preferable technical and clinical success rates. The clinical effect of LAMS on PPC is slightly better than that of WON, but its adverse reactions still need to be verified in a large-sample prospective study.

Objective:To evaluate the effect of early hyperbaric oxygen therapy (HBOT) on neurological function recovery of basal ganglia hemorrhage patients who didn’t receive hematoma evacuation.Methods:A total of 41 basal ganglia hemorrhage patients treated in Nanjing Zijin Hospital and PLA Air Force Hospital of The Eastern Theater Command from January 2015 to January 2020 were included in this study. They did not undergo hematoma evacuation surgery due to small hematoma volume, 18 of whom received early HBOT (treatment group), and the remaining 23 patients received the same HBOT two weeks after hemorrhage (control group). The hematoma volume and the changes of perihematomal edema (PHE) were observed using regular head CT scan, and the incidences of PHE expansion in the two groups were compared on the 10th day after the hemorrhage. All the 41 patients’ neurological functions were assessed by the National Institutes of Health stroke scale (NIHSS) and Glasgow outcome scale (GOS) upon their admission and three months after admission.Results:No re-hemorrhage was found in any patient on the head CT scan. On the 10th day after admission, the incidence of PHE expansion was 16.7% in the treatment group and 91.3% in the control group, respectively, the difference was statistically significant ( P<0.01). After three months of treatment, the NIHSS scores of both groups were decreased, and the GOS scores of both groups were increased. The NIHSS score of the treatment group was lower than that of the control group, while the GOS score in the treatment group was higher than that of the control group, both with statistically significant differences ( P<0.05). Conclusion:Early HBOT is a safe treatment for basal ganglia hemorrhage patients without hematoma evacuation, and it can reduce the occurrence of PHE and improve the prognosis of patients.

Background::Endoscopic ultrasound (EUS)-guided transmural drainage for pancreatic fluid collections (PFCs) has become the first-line treatment with quicker recovery and more minor injury compared with surgery and percutaneous drainage. The efficacy of stents implantation and drainage for different PFCs remains controversial, especially lumen-apposing metal stents (LAMS). This study aimed to compare the efficacy and safety of LAMS drainage for pancreatic pseudocysts (PPC) and walled-off necrosis (WON).Methods::A meta-analysis was performed for LAMS drainage for WON and PPC by systematically searching PubMed, Cochrane, and Embase databases from January 2010 to January 2020. From 2017 to 2019, 12 patients who were treated with LAMS drainage for PFCs in our medical center were also reviewed and included in this study.Results::Combining 11 copies of documents with the data from our medical center, a total of 585 patients with PFCs were enrolled in this meta-analysis, including 343 patients with WON and 242 with PPC. The technical success rate in WON is not significantly different from that of PPC ( P = 0.08 > 0.05). The clinical success of LAMS placement was achieved in 99% vs 89% in PPC and WON, respectively (RR = 0.92, 95% CI: 0.86-0.98, P = 0.01 < 0.05). The further intervention of direct endoscopic necrosectomy was required by 60% of patients in WON group. There was no significant difference in the incidence of adverse events, including infection, bleeding, stent migration and stent occlusion, after LAMS placement between WON and PPC. Conclusions::Endoscopic ultrasound-guided LAMS for PFCs are feasible, effective with preferable technical and clinical success rates. The clinical effect of LAMS on PPC is slightly better than that of WON, but its adverse reactions still need to be verified in a large-sample prospective study.

Objective:To evaluate the effect of early hyperbaric oxygen therapy (HBOT) on neurological function recovery of basal ganglia hemorrhage patients who didn’t receive hematoma evacuation.Methods:A total of 41 basal ganglia hemorrhage patients treated in Nanjing Zijin Hospital and PLA Air Force Hospital of The Eastern Theater Command from January 2015 to January 2020 were included in this study. They did not undergo hematoma evacuation surgery due to small hematoma volume, 18 of whom received early HBOT (treatment group), and the remaining 23 patients received the same HBOT two weeks after hemorrhage (control group). The hematoma volume and the changes of perihematomal edema (PHE) were observed using regular head CT scan, and the incidences of PHE expansion in the two groups were compared on the 10th day after the hemorrhage. All the 41 patients’ neurological functions were assessed by the National Institutes of Health stroke scale (NIHSS) and Glasgow outcome scale (GOS) upon their admission and three months after admission.Results:No re-hemorrhage was found in any patient on the head CT scan. On the 10th day after admission, the incidence of PHE expansion was 16.7% in the treatment group and 91.3% in the control group, respectively, the difference was statistically significant ( P<0.01). After three months of treatment, the NIHSS scores of both groups were decreased, and the GOS scores of both groups were increased. The NIHSS score of the treatment group was lower than that of the control group, while the GOS score in the treatment group was higher than that of the control group, both with statistically significant differences ( P<0.05). Conclusion:Early HBOT is a safe treatment for basal ganglia hemorrhage patients without hematoma evacuation, and it can reduce the occurrence of PHE and improve the prognosis of patients.