Correlation between arterial lactic acid level and complications within 30 days postoperatively in elderly patients undergoing pancreaticoduodenectomy / 中华老年医学杂志

Objective:To evaluate the association between arterial lactate levels and complications within 30 days postoperatively in elderly patients undergoing pancreaticoduodenectomy.Methods:Elderly patients undergoing pancreaticoduodenectomy under selective general anesthesia in Beijing Hospital from July 2019 to December 2021 were enrolled.According to whether complications occurred within 30 days after operation, the patients were divided into complication group(C Group)and no complication group(N Group). General clinical data and lactic acid level before and after surgery were compared between the two groups.And the association between lactic acid level and complications within 30 days postoperatively was evaluated.Results:A total of 70 elderly patients were included in this study, of whom 22 patients had complications with proportion of 31.4%(22/70), including 2 cases of hemorrhage(2.9%, 2/70), one case of infection(1.4%, 1/70), 1 case of pneumonedema(1.4%, 1/70), 13 cases of pancreatic fistula(18.6%, 13/70), 5 cases of all-cause death postoperatively(7.1%, 5/70). There was no significant difference in baseline of arterial lactate level between two groups[0.70(0.50, 0.80)mmol/L vs.0.70(0.50, 1.20)mmol/L, Z=-1.150, P=0.250], while the lactate level at the end of the surgery was significantly higher in group C[1.60(0.90, 2.25)mmol/L]than in group N[1.00(0.80, 1.38)mmol/L]( Z=-2.396, P=0.017). The arterial lactate level at the end of the surgery was a risk factor for postoperative complications by multivariate analyses( OR=2.501, 95% CI: 1.154~5.418, P=0.020). Conclusions:Lactate level at the end of the surgery is related to early postoperative complications(within 30 days postoperatively)in elderly patients undergoing pancreaticoduodenectomy.Paying great attention to lactate monitoring at the end of the surgery may reduce the occurrence of perioperative complications in elderly patients undergoing pancreaticoduodenectomy.

Co-editing PINK1 and DJ-1 Genes Via Adeno-Associated Virus-Delivered CRISPR/Cas9 System in Adult Monkey Brain Elicits Classical Parkinsonian Phenotype / 神经科学通报·英文版

Whether direct manipulation of Parkinson's disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6-10 months), and thus provides a practical transgenic monkey model for future PD studies.

Co-editing PINK1 and DJ-1 Genes Via Adeno-Associated Virus-Delivered CRISPR/Cas9 System in Adult Monkey Brain Elicits Classical Parkinsonian Phenotype / 神经科学通报·英文版

Whether direct manipulation of Parkinson’s disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6–10 months), and thus provides a practical transgenic monkey model for future PD studies.

PD-1/PD-L1 Expressed on T Cell and Bladder Cancer Cell / 中山大学学报(医学科学版)

[Objective] To investigate the characteristics of PD-1/PD-L1 expressed on T cell and bladder cancer cell and clinical significance.[Methods] 64 patients with primary bladder cancer were into experiment group and 10 normal people were into control group.Peripheral bloods were used to test the PD-1 expressed on CD8+ T lymphocytes by flow cytometry.Immunohistochemistry staining was used to detect the PD-L1 expression in tumor and normal specimen.[Results] PD-1 expressed on CD8+T lymphocytes was (2.25 ± 0.60)％ in experiment group and (0.68 ± 0.17)％ in control group,respectively (P ＜ 0.001).And the PD-1 expression on T cell in invasive bladder cancer patient was significant higher than superficial bladder cancer patients [(3.04 ± 0.46)％ vs (0.68± 0.17)％,P ＜ 0.001].The expression of PD-L1 in experiment group was higher than control group,(26/64 vs 0/15,P ＜ 0.001).But there was no different between invasive and superficial bladder cancer patients,(41.3％ vs 38.8％,P ＞ 0.01).[Conclusions] Expression of negative stimulatory molecule PD-1 in CD8+T lymphocytes of peripheral blood is significantly correlated with bladder cancer advanced.Bladder cancer cell was strongly expressed PD-L1,and this expression is not related to cancer advanced.