1.Evaluation of age-adjusted Charlson comorbidity index on prognosis and application timing of Shenfu injection in elderly patients with septic shock
Fuyao NAN ; CaiJun WU ; Jiahui SU ; Junxi LIU ; Linqin MA
Chinese Journal of Emergency Medicine 2023;32(4):546-551
Objective:To evaluate the value of age-adjusted Charlson comorbidity index (aCCI) in the clinical prognosis of sepsis and septic shock in the elderly, and to further explore the role of aCCI in evaluating the timing of Shenfu injection in elderly patients with septic shock.Methods:Clinical data of elderly patients with sepsis and septic shock in Dongzhimen Hospital of Beijing University of Chinese Medicine from January 1, 2019 to January 1, 2022 were retrospectively analyzed. With the median aCCI score of all samples as the cutoff value, the patients were divided into the low aCCI score group and high aCCI score group. The prognosis of elderly patients with septic shock and the application timing of Shenfu injection with aCCI score and sequential organ failure assessment (SOFA) were compared.Results:A total of 61 patients were included, including 31 patients in the high aCCI score group. The proportion of septic shock in elderly sepsis patients was lower in the low aCCI score group ( P < 0.05). The aCCI score (95% CI: 1.229-2.615; P< 0.01) was more valuable than SOFA score (95% CI: 1.035-1.607; P< 0.05) in predicting septic shock in elderly patients with sepsis. The 28-day survival rate in the low aCCI score group was higher than that in the high aCCI score group ( P < 0.05). Both the SOFA score (95% CI: 1.010-1.364) and the aCCI score (95% CI: 1.072-10.501) were independent factors affecting the 28-day survival rate. The use of Shenfu injection was associated with 28-day survival outcome in elderly patients with septic shock (95% CI: 0.012-0.788; P < 0.05). Conclusions:aCCI score is more effective than SOFA score in assessing the risk of shock in elderly patients with septic shock, and has a certain predictive value for the survival and prognosis of elderly patients with sepsis. Shenfu injection may be beneficial to the survival and prognosis of elderly patients with septic shock, but it needs to be further verified by large-scale prospective studies.
2.Study on the mechanism of Danpi-Chishao in the treatment of sepsis based on network pharmacology
Jiahui SU ; Caijun WU ; Fuyao NAN ; Huan XIA ; Yang REN ; Linqin MA
Journal of Chinese Physician 2023;25(2):178-185
Objective:To analyze the mechanism of Danpi-Chishao in treatment of sepsis based on network pharmacology.Methods:The corresponding targets of Danpi-Chishao and sepsis were carried out through TCMSP database, OMIM database and Genecards database. Cystoscope 3.8.2 software was used to construct the " Chinese medicine-active components-target-disease" network diagram. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were carried out by DAVID database. Weisheng cloud platform was used to draw bubble map.Results:A total of 36 effective components of Danpi-Chishao was obtained, mainly including quercetin, kaempferol, baicalin, β-sitosterol, stigmasterol, paeoniflorin and so on. There were 96 potential common key targets between Danpi-Chishao and sepsis, such as prostaglandin-endoperoxide synthase 2 (PTGS2), transcription factor p65 (RELA), phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG), B-cell lymphoma 2 (BCL-2)-associated X (BAX), BCL-2, Caspase-3 (CASP3) with a degree value>4.9. The result of protein-protein interaction (PPI) network analysis showed that there were 10 important target proteins, including alpha serine/threonine-protein kinase (AKT1), interleukin-6 (IL-6), tumor necrosis factor (TNF), interleukin-1β (IL-1β), vascular endothelial growth factor A (VEGFA), cellular tumor antigen p53 (TP53), matrix metalloproteinase-9 (MMP9), CASP3, PTGS2, C-C motif chemokine ligand 2 (CCL2). The pathways obtained by GO and KEGG enrichment analysis included atherosclerosis pathway, advanced glycation end products (AGE)-receptor for advanced glycation end products (RAGE) signal pathway, cancer pathway, tumor necrosis factor signal pathway, hypoxia-inducible factor (HIF) signal pathway, IL-17 signal pathway and other pathway.Conclusions:The mechanism of the intervention effect of Danpi-Chishao on sepsis may be that the active components such as quercetin, kaempferol, paeoniflorin act on target proteins such as PTGS2, RELA, PIK3CG, BAX, BCL2, CASP3, and through TNF-related signal pathway, HIF-1 signal pathway, IL-17 signal pathway, etc. Nonetheless, the conclusion needs further experimental verification.
3.Exploration of animal model of sepsis caused by lung bacterial infection
Caijun WU ; Jun YAN ; Jin LIU ; Yi LIU ; Fuyao NAN ; Jiahui SU ; Linqin MA
Journal of Chinese Physician 2022;24(4):490-495
Objective:Animal models of sepsis are mainly established by cecal ligation and puncture which causes mixed bacterial infections in the abdominal cavity. However in internal clinic, sepsis is more common to be caused by respiratory bacterial infections. Therefore, it is necessary to establish animal models of sepsis caused by lung Infection.Methods:According to the concentration of Staphylococcus aureus (S. aureus) suspension and Pseudomonas aeruginosa (P. aeruginosa) suspension, Sprague Dawley (SD) rats were equally divided into 10 groups, including S-Cont group, S-0.75 group, S-1.5 group, S-3 group, S-6 group and P-Cont group, P-1 group, P-2 group, P-4 group, P-8 group. Rats in the control group were treated with normal saline nasal drip. Rats in each experimental group were infected by nasal dripping bacterial suspension with 0.75×10 8 CFU/ml, 1.5×10 8 CFU/ml, 3×10 8 CFU/ml, 6×10 8 CFU/ml of S. aureus suspension or 1×10 8 CFU/ml, 2×10 8 CFU/ml, 4×10 8 CFU/ml, 8×10 8CFU/ml P. aeruginosa suspension. Our study detected the body temperature (T), blood pressure (BP), heart rate (HR) of rats in each group before and after infection, as well as blood lactic acid (Lac) and procalcitonin (PCT) level after infection. The lung infections of rats in each group were observed by hematoxylin-eosin (HE) staining. Results:The blood pressure(BP) of S-1.5 group, S-3 group, S-6 group and P-8 group was lower than before infection (all P<0.05). The Lac and PCT of each S. aureus experimental group were higher than that of the S-Cont group (all P<0.01); and they showed an increasing trend with the increase of the bacterial suspension concentration ( P<0.05), except for the S-3 and S-6 group ( P>0.05). The Lac and PCT of each P. aeruginosa experimental group were higher than that of the P-Cont group (all P<0.01); and they showed an increasing trend with the increase of the bacterial suspension concentration (all P<0.05), except for the Lac in the P-4 group and P-8 group ( P>0.05). HE staining showed that different degrees of inflammatory infiltration can be seen in the lungs of the experimental rats in each group. Conclusions:Infection of rats by nasal dripping with 3×10 8 CFU/ml of S. aureus suspension or 4×10 8 CFU/ml of P. aeruginosa suspension could establish relatively stable rat sepsis model induced by lung bacterial infection, of which the former could also establish a relatively stable septic shock model.
4.Distribution and prognosis analysis of TCM syndromes elements in elderly patients with sepsis and septic shock
Fuyao NAN ; Caijun WU ; Junxi LIU ; Xiang JI ; Yuanzhen JIAN ; Lan LI ; Wei BI
International Journal of Traditional Chinese Medicine 2024;46(9):1113-1120
Objective:To analyze the distribution pattern of TCM syndrome elements in elderly patients with sepsis and septic shock, as well as the relationship between TCM syndrome elements, Sepsis Sequential Organ Failure Score (SOFA), Acute Physiology and Chronic Health Score Ⅱ (APACHE Ⅱ), and short-term mortality prognosis.Methods:A retrospective analysis was conducted on the clinical data of 58 patients treated in the Emergency Department and ICU of Dongzhimen Hospital of Beijing University of Chinese Medicine and the Third Affiliated Hospital of Beijing University of Chinese Medicine from January 1, 2021, to May 1, 2022. The patients were divided into a sepsis group of 38 cases and a septic shock group of 20 cases based on disease type. Basic information, TCM syndromes, SOFA score, and APACHE Ⅱ score of the two groups were collected. The survival and death statuses of the two groups within 28 days of admission were separately analyzed. Association rule analysis was used to investigate the distribution pattern of TCM syndromes in patients, and logistic regression analysis was performed to explore the relationship between TCM syndromes, SOFA score, APACHE Ⅱ score, and death prognosis.Results:In the sepsis group, the main TCM syndromes included yin deficiency, lung, phlegm, qi deficiency, blood stasis, heat, and yang deficiency; while in the septic shock group, the main TCM syndromes were yin deficiency, lung, yang deficiency, and qi deficiency. Multifactor logistic regression analysis showed that in the sepsis group, liver syndromes [ OR (95% CI)=0.080 (0.011, 0.578), P=0.012], meridians and collaterals [ OR (95% CI)=0.088 (0.011, 0.718), P=0.024], SOFA score [ OR (95% CI)=0.524 (0.310, 0.886), P=0.016], and APACHE Ⅱ score [ OR (95% CI)=0.426 (0.186, 0.977), P=0.044] were independent influencing factors for patient mortality prognosis. In the septic shock group, phlegm [ OR (95% CI)=0.014 (0.001, 0.267), P=0.005], meridians and collaterals [ OR (95% CI)=0.041 (0.003, 0.618), P=0.021], yang deficiency [ OR (95% CI)=0.028 (0.002, 0.427), P=0.010], SOFA score [ OR (95% CI)=0.543 (0.310, 0.950), P=0.032], and APACHE Ⅱ score [ OR (95% CI)=0.633 (0.408, 0.985), P=0.042] were independent influencing factors for patient mortality prognosis. Conclusions:The sepsis group mainly exhibits a mixture of deficiency and excess, while the septic shock group predominantly shows deficiency. Qi deficiency and yin deficiency are consistent throughout the disease progression. Meridians and collaterals, high SOFA score, and high APACHE Ⅱ score in elderly patients with sepsis and septic shock may indicate a poorer prognosis.