1.Pharmacodynamic Substances and Mechanisms of Da Chengqitang in Treating Stroke: A Review
Yizhi YAN ; Xinyi LIU ; Yang DUAN ; Miaoqing LONG ; Chaoya LI ; Qiang LI ; Yi'an CHEN ; Shasha YANG ; Yue ZHANG ; Peng ZENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):297-306
Stroke is the main cause of death and disability among adults in China and is characterized by high incidence, disability, mortality, and recurrence rates. The combination of traditional Chinese and Western medicine has great potential in treating stroke and its sequelae. The classic traditional Chinese medicine prescription Da Chengqitang (DCQT) has a long history and proven efficacy in treating stroke. Clinically, DCQT is often used to treat stroke and its sequelae. However, the number and quality of clinical trials of DCQT in treating stroke need to be improved. Because of the insufficient basic research, the active ingredients and multi-target mechanism of action of DCQT remain unclear. Our research group has previously confirmed that DCQT can effectively reverse neurological damage, reduce iron deposition, and downregulate the levels of pro-inflammatory cytokines in the rat model of hemorrhagic stroke. The treatment mechanism is related to the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated signaling pathway and p38 mitogen-activated protein kinase (MAPK) signaling-mediated microglia activation. To clarify the pharmacodynamic basis and anti-stroke mechanism of DCQT, this article reviews the research progress in the treatment of stroke with DCQT in terms of clinical trials, pharmacodynamic material basis, safety evaluation, and mechanisms of absorbed components. This article summarizes 45 major phytochemical components of DCQT, 11 of which are currently confirmed absorbed components. Among them, emodin, rhein, chrysophanol, aloe-emodin, synephrine, hesperidin, naringin, magnolol, and honokiol can be used as quality markers (Q-markers) of DCQT. The mechanism of DCQT in treating stroke is complex, involving regulation of inflammatory responses, neuronal damage, oxidative stress, blood-brain barrier, brain-derived neurotrophic factor, and anti-platelet aggregation. This article helps to deeply understand the pharmacodynamic basis and mechanism of DCQT in treating stroke and provides a theoretical basis for the clinical application of DCQT in treating stroke and the development of stroke drugs.
2.Effects of acupuncture on serotonin, histamine, substance P, and tryptase levels at sensitized points in model rats with knee osteoarthritis
Jiayi Yang ; Zidong Wang ; Jing Jiang ; Huiling Tian ; Shun Wang ; Yizhi Liu ; Zumao Cao ; Changqing Joseph Yang ; Zhigang Li
Journal of Traditional Chinese Medical Sciences 2024;11(4):500-512
Objective:
To elucidate the differences in manual acupuncture effectiveness at sensitized points by investigating the mechanisms of local skin action at different sensitization points in rats with knee osteoarthritis (KOA).
Methods:
Forty Sprague–Dawley rats were equally divided into control, model (1 mg of monoiodoacetate into the right knee joint cavity), sham operation, manual acupuncture at right Tianjing acupoint (MAR-SJ 10), and left SJ 10 groups. Safranine-O and fast green staining were used to assess the modeling. The morphological and functional changes in mast cells (MCs) were assessed during acupoint sensitization using toluidine blue and immunofluorescence staining. The levels of serotonin, histamine, substance P (SP), and tryptase at skin acupoints and serum levels of IL-β, IL-6, and TNF-α were detected using ELISA.
Results:
After 14 days of treatment, the number of MCs and their degranulation rates were statistically higher in the model group than in the control group (both P < .001). After applying acupuncture, the levels of 5-HT, HA, and SP at skin acupoints were lower than those in the model group (all P < .05), and tryptase level was higher (both P < .05). Tryptase level was higher on the skin at the MAL-SJ 10 acupoint than that on the MAR-SJ 10 acupoint (P = .004). Compared with the model group, the serum levels of IL-1β, IL-6, and TNF-α in the MAR-SJ 10 and MAL-SJ 10 groups were lower (all P < .05).
Conclusion
Acupuncture at KOA-sensitized acupoints mitigates joint injury in KOA rats and may bidirectionally regulate local MCs of these acupoints. This finding not only enhances the reference value of sensitizing points in clinical diagnosis and treatment, but also contributes to the understanding of the biological mechanisms underlying acupuncture intervention at sensitizing points.
3.Comparative Study on the Pharmacodynamics of Xiangzhu Fanggan Formula (香术防感方) by Sniffing and Nasal Drops for Prevention of Influenza A H1N1 Virus Infection in Mice
Yue ZHANG ; Yizhi DONG ; Haoyue LI ; Xinxin WU ; Xiaolei LI ; Jing ZHAO
Journal of Traditional Chinese Medicine 2024;65(12):1279-1286
ObjectiveTo compare the effectiveness and mechanism of Xiangzhu Fanggan Formula (香术防感方) by sniffing and nasal drops for preventing influenza A H1N1flu. MethodsFifty-six BALB/c mice were randomly divided into normal group, model group, zanamivir group, high-concentration sachet group, low-concentration sachet group, high-concentration nasal drops group, and low-concentration nasal drops group, with 8 mice in each group. In the low- and high-concentration sachet groups, 15 g and 30 g of Xiangzhu Fanggan Formula sachet were used for sniffing for 24 h per day; while in the low- and high-concentration nasal drops groups, nasal drops of Xiangzhu Fanggan Formula were given at a concentration of 0.11 and 0.22 g/ml, 20 μl each time, twice a day; in the zanamivir group, zanamivir was given at a concentration of 1.025 mg/ml of 20 μl each time, twice a day; in the normal group and the model group, nasal drops of normal saline were given at 20 μl each time, twice a day. Each group was given prophylactic intervention for 5 days. On day 5, 1 h after the administration of the drug, the mice in all groups except the normal group received 35 μl of 50 LD50 A/PR/8/34/H1N1 viral solution as nasal drops to prepare influenza A H1N1 model mice. The body mass of the mice was recorded and the rate of change of body mass was calculated daily from day 5 to day 9 of the experiment, and the general status was observed. The mice were sampled on day 9, and the lung index and the inhibition rate of lung index were calculated; HE staining was used to detect pathological changes in lung tissues and to score lung tissue lesions; RT-qPCR was used to detect viral load in lung tissues; and ELISA was used to detect secretory immunoglobulin A (sIgA) and serum tumour necrosis factor α (TNF-α) and interleukin 2 (IL-2), interleukin 6 (IL-6), and interferon γ (IFN-γ) in the lavage fluid of the upper respiratory tract. ResultsOn days 7, 8 and 9 of the experiment, the rate of change in body mass of mice in the model group significantly lower than that in the normal group at the same time points (P<0.05 or P<0.01). On days 8 and 9 of the experiment, the rate of change in body mass of mice in the zanamivir group and the high-concentration nasal drops group increased when compared with the model group (P<0.05 or P<0.01). Compared with the normal group, mice in the model group had significantly higher lung index, lung tissue lesion score, lung tissue viral load, significantly higher serum TNF-α, IL-6, IL-2, IFN-γ levels, and significantly lower sIgA levels in the upper respiratory lavage fluid (P<0.01). Compared with the model group, the lung index and lung tissue viral load reduced, serum IFN-γ, TNF-α, IL-2, IL-6 levels reduced, and sIgA levels increased in the zanamivir group and the high-concentration nosal drops group (P<0.05 or P<0.01); except for low-concentration sachet group, lung tissue lesion scores of the drug intervention groups reduced compared with those of the model group (P<0.01). Compared with the zanamivir group, the lung index increased in the low-concentration sachet group and the low- and high-concentration nasal drops groups, and the serum TNF-α and IL-2 levels increased in all Xiangzhu Fanggan Formula intervention groups (P<0.05 or P<0.01). Compared with high-concentration nasal drops group, serum TNF-α and IFN-γ levels elevated in the high-concentration increased group, and lung tissue viral load elevated in the low-concentration nasal drops group (P<0.05 or P<0.01). The lung index inhibition rate was 80.84% in the zanamivir group, 41.61% and 17.90% in the high- and low-concentration sachet groups, and 35.40% and 25.40% in the high- and low-concentration nasal drops groups, respectively. HE staining showed that the lung tissues of the model group showed thickening of alveolar septa, alveolar collapse, and infiltration of inflammatory cells; whereas, in each drug intervention group, the inflammation of the lung tissues of the mice and the damage reduced, and the most obvious improvement was in the zanamivir group and the high-concentration nasal drops group. ConclusionXiangzhu Fanggan Formula by sniffing and nasal drops could both prevent influenza A H1N1 virus infection, with antiviral and anti-inflammatory effects, also could improve the pathological damage of lung tissue, and improve the immunity of respiratory mucosa. The nasal drops may be better than sachets in inhibiting inflammatory response, especially the high-concentration nasal drops showed more effective.
4.Effect of Yiqi Huoxue Prescription on cAMP/Epac1/Rap1 Signaling Pathway in Coronary Heart Disease Rats with Qi Deficiency and Blood Stasis Syndrome
Huaying WU ; Kai DENG ; Jing LI ; Yizhi MAO ; Liang LI ; Qinghua PENG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):107-116
ObjectiveBased on cyclic adenosine monophosphate (cAMP)/cAMP-regulated guanine nucleotide exchange factor 1 (Epac1)/Ras-homologous protein 1 (Rap1) signaling pathway to explore the myocardial protective mechanism of Yiqi Huoxue prescription on coronary heart disease (CHD) rats with Qi deficiency and blood stasis syndrome. MethodEighty-eight specific-pathogen-free (SPF) grade male Sprague-Dawley (SD) rats were divided into a sham operation group (n=12) and an experimental group (n=76) according to the random number table. The experimental group underwent a restricted diet and exhaustive swimming combined with left anterior descending (LAD) coronary artery ligation to construct a model of CHD with Qi deficiency and blood stasis syndrome, and electrocardiograms (ECGs) of rats before and after the LAD operation were collected. After the model was successfully established, the rats were randomly divided into model group, Yiqi Huoxue prescription low-dose group (4.28 g·kg-1), medium-dose group (8.55 g·kg-1), high-dose group (17.1 g·kg-1), and Western medicine group (isosorbide mononitrate tablets, 3.6 mg·kg-1). Rats were intragastrically administered assigned drugs for 4 weeks consecutively, while the sham operation group and the model group were administered with equal volumes of double distilled water. Twenty-four hours after the final administration, the rats were anesthetized with isoflurane to detect the left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular fractional shortening (FS, %), and ejection fraction (EF, %) by echocardiography. Blood samples were collected from the abdominal aorta for hemorheological measurements, and plasma cAMP levels were determined using enzyme-linked immunosorbent assay (ELISA). Myocardial tissue was collected for hematoxylin-eosin (HE) staining and Masson staining to observe myocardial pathological damage, and a transmission electron microscope was used to observe ultrastructural changes of myocardial tissue, fluorescent quantitative real-time polymerase chain reaction (Real-time PCR) was used to detect the expressions of myocardial Epac1, Rap1 GTPase activating protein (Rap1GAP) and Rap1 mRNA, and Western blot was used to detect the expressions of myocardial Epac1, Rap1GAP and Rap1 protein. ResultCompared with those in the sham operation group, LVEDD and LVISD of rats in the model group significantly increased (P<0.01), and the ratios of EF and FS significantly decreased (P<0.01), indicating symptoms of heart function decline, referred to as "heart Qi deficiency". The viscosity of whole blood and plasma significantly increased (P<0.01), and the content of cAMP significant increased (P<0.01). In addition, there was a significant proliferation of collagen fibers in myocardial tissue (P<0.01), and the ultrastructure of the myocardial tissue was severely damaged, indicating pathological changes consistent with "blood stasis". Real-time PCR results showed that Epac1 and Rap1 mRNA levels in the model group were significantly reduced (P<0.01), while Rap1GAP mRNA levels were significantly increased (P<0.01). Western blot analysis showed a significant decrease in Epac1 protein expression (P<0.01) and a significant increase in Rap1GAP protein expression (P<0.05). Compared with the model group, Yiqi Huoxue prescription improved cardiac function, reduced blood viscosity, lowered plasma cAMP levels, decreased collagen fiber proliferation, and improved myocardial ultrastructure damage in CHD rats with Qi deficiency and blood stasis syndrome. The high-dose group showed the most significant effects. In the high-dose group, Epac1 mRNA and protein expression levels significantly increased (P<0.01), Rap1 mRNA expression significantly increased (P<0.01), and Rap1GAP mRNA and Rap1GAP/Rap1 protein expression levels significantly decreased (P<0.05, P<0.01). ConclusionYiqi Huoxue prescription can improve cardiac function, reduce blood viscosity and plasma cAMP levels, improve myocardial damage, and reduce collagen fiber proliferation in CHD rats with Qi deficiency and blood stasis syndrome. The myocardial protection mechanism may be related to the regulation of the cAMP/Epac1/Rap1 signaling pathway.
5.CACNA1C rs58619945 genotype influences the cortical thickness of attention network among patients with Bipolar Ⅰ disorder
Xiaofei ZHANG ; Xiaoyu LIANG ; Xiaofang CHENG ; Jianshan CHEN ; Wenhao DENG ; Yizhi ZHANG ; Liqian CUI ; Xiongchao CHENG ; Xuan LI ; Chanjuan YANG ; Biyu YE ; Liping CAO
Chinese Journal of Medical Genetics 2024;41(9):1045-1052
Objective:To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). Methods:From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. This study was approved by the Medical Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University(Ethics No. 2023-056). Results:Compared with the HC group, the BD-Ⅰ patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex( P<0.05). A significant interaction between the CACNA1C genotype and the cortical thickness(HC vs.BD) of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted( P<0.05). Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex( P<0.05), and right superior temporal cortex predominantly among carriers of the BD-Ⅰ G allele. Conclusion:The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.
6.Differential diagnosis of post-thrombectomy high-density shadow within the brain parenchyma displayed on early plain CT scan in patients with ischemic stroke
Yuan MA ; Peicheng LI ; Qingsong LI ; Huijuan SHI ; Yizhi LIU ; Long CHEN
Journal of Interventional Radiology 2024;33(8):829-833
Objective To differentiate cerebral parenchymal hemorrhage from contrast extravasation based on the imaging characteristics of a high-density shadow within the brain parenchyma,which is demonstrated on early(within 24 hours)plain CT scan in patients with acute ischemic stroke after receiving mechanical thrombectomy(MT).Methods The clinical data of 77 patients with ischemic stroke caused by acute large-vessel occlusion,who received MT and whose early plain CT scan(performed within 24 hours after MT)showed a high-density shadow within the brain parenchyma,were retrospectively analyzed.According to the results of CT reexamination performed at 24-48 hours after treatment,the patients were divided into parenchymal hemorrhage group(n=38,43 sites)and pure contrast extravasation group(n=39,47 sites).The direct signs(including location distribution,maximum CT value,volume,mixed density sign)and the indirect signs(including local space-occupying effect,intraventricular high density,subarachnoid high density)of the post-thrombectomy intraparenchymal high-density(PTIH)shadow displayed on early CT images after MT were analyzed.The differences in imaging characteristics between the two groups were analyzed by using t-test,Mann-Whitney rank sum test,chi-square test,Fisher exact test and multivariate logistic regression analysis.Results The space-occupying effect(28/38 versus 9/39,P=0.003)and intraventricular high density lesion(5/38 versus 0/39,P=0.025)were more likely to occur in the parenchymal hemorrhage group than in the pure contrast extravasation group.The newly-developed 90 PTIH lesions included 43 parenchymal hemorrhage foci and 47 contrast extravasation foci.Multivariate logistic regression analysis showed that the differences in the PTIH volume and mixed density sign between the two groups were statistically significant(both P<0.05,OR=2.93 and OR=9.24 respectively).The optimal critical value of PTIH volume for diagnosing cerebral parenchymal hemorrhage was 9.3 cm3.Conclusion The space-occupying effect and intraventricular high density are the indirect signs for judging a newly-developed PTIH to be a cerebral parenchymal hemorrhage.PTIH volume ≥9.3 cm3 and mixed density sign are the direct signs for judging a newly-developed PTIH to be a cerebral parenchymal hemorrhage.
7.Correlation between the growth speed of cerebral infarction and the symptomatic intracranial hemorrhage occurring in patients with acute anterior circulation large vessel occlusion after mechanical thrombectomy
Xusen YANG ; Peicheng LI ; Long CHEN ; Bo LI ; Yizhi LIU ; Chen YUAN ; Wanci LI ; Yun DING
Journal of Interventional Radiology 2024;33(11):1170-1174
Objective To evaluate the impact of the growth speed of cerebral infarction on the occurrence of symptomatic intracranial hemorrhage(sICH)in patients with acute anterior circulation ischemic stroke after mechanical thrombectomy.Methods The clinical data of patients with acute ischemic stroke(AIS),who received mechanical thrombectomy at the First Affiliated Hospital of Soochow University of China from June 2016 to December 2022,were retrospectively analyzed.After thrombectomy,the patients were divided into sICH group and non-sICH group according to Heidelberg criteria.The clinical data and imaging findings were compared between the two groups.Multivariate logistic regression analysis was used to identify the independent risk factors for sICH after thrombectomy,and the area under the receiver operating characteristic curve(AUC)was used to evaluate the efficacy of the growth speed of cerebral infarction in predicting sICH.Results A total of 218 patients were enrolled in this study,sICH group had 23 patients and non-sICH group had 195 patients.The differences in NIHSS score,collateral circulation status,core infarction volume,and growth speed of cerebral infarction between the two groups were statistically significant(all P<0.05).Multivariate logistic regression analysis showed that rapid growth speed of cerebral infarction was an independent risk factor for sICH occurring after mechanical thrombectomy.For predicting sICH,the sensitivity and specificity of the growth speed of cerebral infarction were 78.3%and 69.7%respectively,with an AUC of 0.751 and a predicted value of 7.6 mL/h.Conclusion The rapid growth speed of cerebral infarction is a predictive factor for sICH occurring after mechanical thrombectomy in patients with acute anterior circulation ischemic stroke.The risk of sICH becomes higher after mechanical thrombectomy when the growth speed of cerebral infarction is faster than 7.6 mL/h.
8.Effects of cerium oxide nanoenzyme-gelatin methacrylate anhydride hydrogel in the repair of infected full-thickness skin defect wounds in mice
Ya'nan GU ; Xianghao XU ; Yanping WANG ; Yutao LI ; Zhen LIANG ; Zhou YU ; Yizhi PENG ; Baoqiang SONG
Chinese Journal of Burns 2024;40(2):131-140
Objective:To investigate the effects of cerium oxide nanoenzyme-gelatin methacrylate anhydride (GelMA) hydrogel (hereinafter referred to as composite hydrogel) in the repair of infected full-thickness skin defect wounds in mice.Methods:This study was an experimental study. Cerium oxide nanoenzyme with a particle size of (116±9) nm was prepared by hydrothermal method, and GelMA hydrogel with porous network structure and good gelling performance was also prepared. The 25 μg/mL cerium oxide nanoenzyme which could significantly promote the proliferation of human skin fibroblasts and had high superoxide dismutase activity was screened out. It was added to GelMA hydrogel to prepare composite hydrogel. The percentage of cerium oxide nanoenzyme released from the composite hydrogel was calculated after immersing it in phosphate buffer solution (PBS) for 3 and 7 d. The red blood cell suspension of mice was divided into PBS group, Triton X-100 group, cerium oxide nanoenzyme group, GelMA hydrogel group, and composite hydrogel group, which were treated with corresponding solution. The hemolysis of red blood cells was detected by microplate reader after 1 h of treatment. The bacterial concentrations of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli were determined after being cultured with PBS, cerium oxide nanoenzyme, GelMA hydrogel, and composite hydrogel for 2 h. The sample size in all above experiments was 3. Twenty-four 8-week-old male BALB/c mice were taken, and a full-thickness skin defect wound was prepared in the symmetrical position on the back and infected with MRSA. The mice were divided into control group without any drug intervention, and cerium oxide nanoenzyme group, GelMA hydrogel group, and composite hydrogel group applied with corresponding solution, with 6 mice in each group. The wound healing was observed on 3, 7, and 14 d after injury, and the remaining wound areas on 3 and 7 d after injury were measured (the sample size was 5). The concentration of MRSA in the wound exudation of mice on 3 d after injury was measured (the sample size was 3), and the blood flow perfusion in the wound of mice on 5 d after injury was observed using a laser speckle flow imaging system (the sample size was 6). On 14 d after injury, the wound tissue of mice was collected for hematoxylin-eosin staining to observe the newly formed epithelium and for Masson staining to observe the collagen situation (the sample size was both 3). Results:After immersion for 3 and 7 d, the release percentages of cerium oxide nanoenzyme in the composite hydrogel were about 39% and 75%, respectively. After 1 h of treatment, compared with that in Triton X-100 group, the hemolysis of red blood cells in PBS group, GelMA hydrogel group, cerium oxide nanoenzyme group, and composite hydrogel group was significantly decreased ( P<0.05). Compared with that cultured with PBS, the concentrations of MRSA and Escherichia coli cultured with cerium oxide nanoenzyme, GelMA hydrogel, and composite hydrogel for 2 h were significantly decreased ( P<0.05). The wounds of mice in the four groups were gradually healed from 3 to 14 d after injury, and the wounds of mice in composite hydrogel group were all healed on 14 d after injury. On 3 and 7 d after injury, the remaining wound areas of mice in composite hydrogel group were (29±3) and (13±5) mm 2, respectively, which were significantly smaller than (56±12) and (46±10) mm 2 in control group and (51±7) and (38±8) mm 2 in cerium oxide nanoenzyme group (with P values all <0.05), but was similar to (41±5) and (24±9) mm 2 in GelMA hydrogel group (with P values both >0.05). On 3 d after injury, the concentration of MRSA on the wound of mice in composite hydrogel group was significantly lower than that in control group, cerium oxide nanoenzyme group, and GelMA hydrogel group, respectively (with P values all <0.05). On 5 d after injury, the volume of blood perfusion in the wound of mice in composite hydrogel group was significantly higher than that in control group, cerium oxide nanoenzyme group, and GelMA hydrogel group, respectively ( P<0.05). On 14 d after injury, the wound of mice in composite hydrogel group basically completed epithelization, and the epithelization was significantly better than that in the other three groups. Compared with that in the other three groups, the content of collagen in the wound of mice in composite hydrogel group was significantly increased, and the arrangement was also more orderly. Conclusions:The composite hydrogel has good biocompatibility and antibacterial effect in vivo and in vitro. It can continuously sustained release cerium oxide nanoenzyme, improve wound blood perfusion in the early stage, and promote wound re-epithelialization and collagen synthesis, therefore promoting the healing of infected full-thickness skin defect wounds in mice.
9.Analysis of effects and influencing factors of continuous renal replacement therapy in severe burn patients complicated with acute kidney injury
Xue HENG ; Changmin LI ; Wei LIU ; Ning LI ; Zhiqiang YUAN ; Yizhi PENG ; Haisheng LI ; Gaoxing LUO
Chinese Journal of Burns 2024;40(5):468-475
Objective:To preliminarily evaluate the effects and analyze the influencing factors of continuous renal replacement therapy (CRRT) in severe burn patients complicated with acute kidney injury (AKI).Methods:This study was a retrospective case series study. From January 2010 to December 2020, 79 severe burn patients complicated with AKI who received CRRT and met the inclusion criteria were admitted to the First Affiliated Hospital of Army Medical University (the Third Military Medical University). The general data (the same below) of all patients were collected, including gender, age, body mass index, burn area, burn index, cause of injury, whether combined with inhalation injury, acute physiology and chronic health status evaluation Ⅱ (APACHE Ⅱ) score and sepsis-related organ failure assessment (SOFA) score on admission, admission time after burn, and time of AKI after admission. The total efficacy of CRRT, including overall effective rate, complete effective rate, partial effective rate, ineffective rate, and deterioration rate, creatinine, urea, cystatin C, and fluid overload rate before and after treatment, in-hospital mortality, predictive mortality based on Baux scoring model, the most common cause of death, and length of hospital stay were recorded. According to the effect of CRRT, the patients were divided into effective group (42 patients) and ineffective group (37 patients). The general information of patients, the time to initiate CRRT after the occurrence of AKI, the duration of CRRT, etiology of AKI, AKI stage before CRRT initiation, CRRT mode, anticoagulant type, and in-hospital mortality were compared between the two groups of patients. The independent influencing factors for CRRT in severe burn patients complicated with AKI were screened. According to the etiology of AKI, the patients were divided into prerenal group (22 patients) and renal group (57 patients). The general information of patients, the time to initiate CRRT after the occurrence of AKI, the duration of CRRT, and total efficacy of CRRT (except for the most common cause of death) were compared between the two groups of patients.Results:Among the 79 patients, 73 cases were male and 6 cases were female, with age of (46±14) years, body mass index of (24.0±2.9) kg/m 2, total burn area of (69±26)% total body surface area (TBSA), full-thickness burn area of (44±25)%TBSA, and burn index of 57 (36, 76). There were 36 cases of flame burns, 19 cases of electrical burns, 16 cases of hydrothermal burns, 6 cases of explosive burns, and 2 cases of chemical burns. Thirty-nine patients were complicated with inhalation injury. The APACHE Ⅱ score was 16 (12, 18) and the SOFA score was 11 (5, 13) on admission. The patients were admitted to the hospital on 0 (0, 2) d after burn, and AKI occurred on 0 (0, 6) d after admission. The overall effective rate of CRRT was 53.16% (42/79), the complete effective rate was 30.38% (24/79), the partial effective rate was 22.78% (18/79), the ineffective rate was 31.65% (25/79), and the deterioration rate was 15.19% (12/79). The creatinine and urea of patients after treatment were significantly lower than those before treatment (with Z values of -3.26 and -2.54, respectively, P<0.05); there were no statistically significant differences in the cystatin C and fluid overload rate of patients before and after treatment ( P>0.05). The in-hospital mortality of patients was 17.72% (14/79), and the predictive mortality based on Baux scoring model was 75.10% (18.94%, 91.84%). The most common cause of death was multiple organ failure, and the length of hospital stay was 39.43 (11.52, 110.58) d. There were statistically significant differences in the full-thickness burn area, the duration of CRRT, and etiology of AKI of patients between effective group and ineffective group (with Z values of -1.99 and -2.90, respectively, χ2=5.58, P<0.05). There were no statistically significant differences in the other indicators ( P>0.05). The etiology of AKI and full-thickness burn area were the independent influencing factors for CRRT in severe burn patients complicated with AKI (with odds ratios of 4.21 and 1.03, respectively, 95% confidence intervals of 1.20-14.80 and 1.00-1.05, respectively, P<0.05). There were statistically significant differences in the cause of injury, overall effective rate of CRRT, total burn area, burn index, admission time after burn, time of AKI after admission, the time to initiate CRRT after the occurrence of AKI, and predictive mortality based on Baux score model of patients between prerenal group and renal group (with χ2 values of 12.59 and 5.58, respectively, Z values of 2.46, 2.43, -2.43, -4.03, -3.01, and -2.31, respectively, P<0.05). Before treatment, urea and cystatin C of patients in renal group were significantly higher than those in prerenal group (with Z values of -2.98 and -2.77, respectively, P<0.05), and the liquid overload rate was significantly lower than that in prerenal group ( Z=-2.99, P<0.05); after treatment, the cystatin C of patients in renal group was significantly higher than that in prerenal group ( Z=-2.08, P<0.05); there were no statistically significant differences in the other indicators ( P>0.05). Conclusions:CRRT can significantly improve renal function, avoid fluid overload, and alleviate renal injury in severe burn patients complicated with AKI. Prerenal AKI is the main independent influencing factor leading to ineffective CRRT.
10.Relationship between the lowest hemoglobin value during hospitalization and the prognosis in patients with extensive burns
Fangqing ZUO ; Jiaqing SU ; Yang LI ; Lijuan ZHANG ; Yingying LAN ; Yu CHEN ; Yali GONG ; Yajie CHEN ; Junda LI ; Yizhi PENG ; Gaoxing LUO ; Zhiqiang YUAN
Chinese Journal of Burns 2024;40(6):543-550
Objective:To investigate the relationship between the lowest hemoglobin value during hospitalization and the prognosis in patients with extensive burns, in order to explore the hemoglobin warning threshold for blood transfusion in patients with extensive burns.Methods:The research was a retrospective observational study. From October 2012 to October 2022, 288 patients with extensive burns who met the inclusion criteria were admitted to the First Affiliated Hospital of Army Medical University (the Third Military Medical University), including 243 males and 45 females, aged 18 to 65 years. These patients were assigned to the death group ( n=54) and the survival group ( n=234) based on their final prognosis. The clinical data including gender, age, body mass index, total burn area, full-thickness burn area, time of first operation after injury, preoperative prothrombin time (PT) and activated partial thromboplastin time (APTT) and hemoglobin level of the first surgery, complication of inhalation injury, number of surgeries, total surgical area, total surgical time, total length of hospital stay, and highest procalcitonin value, lowest platelet count and hemoglobin values, and occurrence of sepsis during hospitalization were compared between the two groups of patients. According to the lowest hemoglobin value during hospitalization, the patients were assigned to <65 g/L group, ≥65 g/L and <75 g/L group, ≥75 g/L and <85 g/L group, and ≥85 g/L group. The total length of hospital stay, mortality and incidence of sepsis during hospitalization, and mortality within 90 days after injury were compared among the four groups of patients. The relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns was analyzed using a restricted cubic spline model before and after adjusting covariates. A logistic regression model was adopted to analyze the relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns after adjusting covariates, with the lowest hemoglobin value during hospitalization as a continuous variable and a categorical variable, separately. Results:Compared with those in survival group, the total burn area, full-thickness burn area, and total surgical area of patients in death group were significantly increased, the preoperative APTT of the first surgery was significantly prolonged, the number of surgeries was significantly reduced, the total length of hospital stay was significantly shortened, the highest procalcitonin value during hospitalization was significantly increased, the lowest platelet count and hemoglobin values during hospitalization were significantly decreased, and the incidence proportion of sepsis during hospitalization was significantly increased (with Z values of -6.72, -5.40, -2.15, -2.99, -2.21, -7.84, -6.23, -7.03, and -3.43, respectively, χ2=161.95, P values all <0.05). There were no statistically significant differences in the other clinical data of patients between the two groups ( P>0.05). There were statistically significant differences in mortality and incidence of sepsis during hospitalization, and mortality within 90 days after injury of patients among the four groups divided according to the lowest hemoglobin value during hospitalization (with χ2 values of 12.12, 15.93, and 10.62, respectively, P<0.05). There was no statistically significant difference in the total length of hospital stay of patients among the four groups ( P>0.05). The restricted cubic spline model analysis revealed an approximately linear relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns before and after adjusting covariates (with χ2 values of 0.81 and 0.75, respectively, P>0.05). After adjusting covariates, the logistic regression model analysis showed that the mortality risk of patients with extensive burns increased with decreasing hemoglobin when the lowest hemoglobin value during hospitalization was analyzed as a continuous variable (with odds ratio of 0.96, with 95% confidence interval of 0.92 to 0.99, P<0.05). When using the median value of 75.5 g/L as the cut-off value for categorizing the lowest hemoglobin value during hospitalization, there was no statistically significant difference in the mortality risk between patients with hemoglobin <75.5 g/L and those with hemoglobin ≥75.5 g/L ( P>0.05). When the patients were divided into four groups based on the lowest hemoglobin value during hospitalization as above, using ≥85 g/L group as a reference, only patients in <65 g/L group had a significantly increased mortality risk (with odds ratio of 5.37, with 95% confidence interval of 1.57 to 18.29, P<0.05). Conclusions:There is an approximately linear correlation between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns. When the hemoglobin level drops to 65 g/L or lower, the mortality risk of patients increases significantly, suggesting that a hemoglobin level of 65 g/L could serve as a warning threshold for blood transfusion in patients with extensive burns.


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