1.Trilogy of drug repurposing for developing cancer and chemotherapy-induced heart failure co-therapy agent.
Xin CHEN ; Xianggang MU ; Lele DING ; Xi WANG ; Fei MAO ; Jinlian WEI ; Qian LIU ; Yixiang XU ; Shuaishuai NI ; Lijun JIA ; Jian LI
Acta Pharmaceutica Sinica B 2024;14(2):729-750
Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.
2.Impact of pembrolizumab combined with chemotherapy on angiogenesis and circulating endothelial cells in patients with advanced non-small cell lung cancer
Xi JIANG ; Yongcun WU ; Yan LIANG ; Li CHU ; Yingxin DUAN ; Lijun WANG ; Junjie HUO
Journal of International Oncology 2024;51(2):89-94
Objective:To explore the impact of pembrolizumab combined with chemotherapy on angiogenesis and circulating endothelial cells in patients with advanced non-small cell lung cancer (NSCLC) .Methods:The retrospective analysis of clinical data from 121 patients diagnosed with advanced NSCLC who were admitted to the Second Affiliated Hospital of Xingtai Medical College from August 2021 to January 2023 was conducted. These patients were divided into a control group ( n=57) and an observation group ( n=64) based on the designated treatment protocol. Specifically, individuals in the control group received standard chemotherapy (cisplatin+paclitaxel), while those in the observation group underwent penpilimab therapy in conjunction with conventional chemotherapy. The comparative assessment encompassed short-term clinical efficacy, quality of life, immune function parameters, angiogenic factors [including endostatin, insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF) ], circulating endothelial cells, and adverse reactions within the two groups. Results:After 6 courses of treatment, the objective response rate [67.19% (43/64) vs. 49.12% (28/57) ] and disease control rate [87.50% (56/64) vs. 70.18% (40/57) ] in observation group were higher than those in control group, with statistically significant differences ( χ2=4.06, P=0.044; χ2=5.52, P=0.019). The quality of life score of observation group [ (56.77±6.81) points] was significantly higher than that of control group [ (47.73±8.23) points], with a statistically significant difference ( t=6.61, P<0.001) ; The T cell subgroup CD3 + levels [ (63.59±9.00) % vs. (53.06±8.80%), t=6.49, P<0.001], CD4 + levels [ (46.54±8.20) % vs. (30.74±7.32) %, t=11.13, P<0.001] and CD4 +/CD8 + ratio (1.90±0.36 vs. 1.21±0.28, t=11.66, P<0.001) in observation group were significantly higher than those in control group, with statistically significant differences; Endostatin in observation group [ (48.99±3.43) μmol/L] was significantly higher than that in control group [ (31.35±3.87) μmol/L], with a statistically significant difference ( t=26.58, P<0.001), IGF-1 [ (102.31±20.35) μg/L vs. (134.98±19.02) μg/L] and VEGF [ (31.70±4.32) pg/ml vs. (58.71±5.99) pg/ml] were significantly lower in observation group than those in control group, with statistically significant differences ( t=18.73, P<0.001; t=28.14, P<0.001). The number of circulating endothelial cells in observation group [ (58.77±10.03) /ml] was significantly lower than that in control group [ (87.01±8.01) /ml], with a statistically significant difference ( t=17.20, P<0.001). During treatment, there were no statistically significant differences in the incidence of gastrointestinal reaction ( χ2=0.01, P=0.908), leukopenia ( χ2=0.64, P=0.424), thrombocytopenia ( χ2=0.28, P=0.597), anemia ( χ2=1.66, P=0.197), nephrotoxicity ( χ2=0.64, P=0.424), skin rash ( χ2=1.33, P=0.249) between the two groups. Conclusion:The combination therapy of pembrolizumab and chemotherapy for the treatment of advanced NSCLC has demonstrated noteworthy effectiveness. This regimen has the potential to enhance patients' immune functionality, ameliorate their overall quality of life, suppress angiogenesis, and exhibits a commendable profile of safety and reliability.
3.Circular RNAs are involved in the pathogenesis of osteoarthritis through intracellular mechanisms
Lijun ZHOU ; Keyuan ZHANG ; Xi WANG ; Li YU ; Feihu XU ; Hong DING ; Hairong MA
Chinese Journal of Tissue Engineering Research 2024;28(35):5716-5722
BACKGROUND:Currently,there is no drug that can completely cure osteoarthritis and its pathogenesis is still unclear.Circular RNAs(circRNAs)are differentially expressed in patients with osteoarthritis and are closely associated with various pathological processes in osteoarthritis.circRNAs play an important role in various physiological and pathological processes,such as chondrocyte homeostasis,extracellular matrix formation,and inflammatory response. OBJECTIVE:To mainly review the effects of circRNAs on pathological factors related to osteoarthritis,as well as the types and expression levels of circRNAs in osteoarthritis. METHODS:Related articles published from 1976 to August 2023 were retrieved from CNKI,WanFang,VIP,PubMed,Medline,Web of Science and Elsevier databases.The keywords were"osteoarthritis,circular RNA,non-coding RNA,synovial tissue,chondrocytes"in Chinese and English,respectively.All the relevant articles were screened,summarized,analyzed,and finally 69 papers were included in the review. RESULTS AND CONCLUSION:circRNAs are non-coding RNAs widely found in eukaryotic cells,with covalently closed continuous loop structure,but with no 5'hat structure and 3'poly A tail,which are involved in multi-gene and multi-target regulatory networks and cannot be degraded by nucleic acid exonucleases(RNase R).circRNAs have a high abundance,high conservativeness and stability,and cell and tissue specificity.circRNAs have biological functions such as acting as molecular sponges for miRNAs,regulating linear RNA transcription and RNA shearing,interacting with RNA-bound proteins,and translating proteins.circRNAs regulate chondrocyte apoptosis and proliferation,degradation of cartilage extracellular matrix,and inflammation and other physiopathologic processes.circRNAs are expected to become biomarkers and potential therapeutic targets for clinical diagnosis and prognosis of osteoarthritis,and may become a new strategy for clinical treatment of osteoarthritis in the future.
4.Mid-term analysis of prospective cohort study of rivaroxaban in preventing CRT in breast cancer
Die SANG ; Shanmin FAN ; Shiyu LI ; Jintao ZHANG ; Hengmin WANG ; Xiaohui ZHAO ; Lijun ZHENG ; Ping LIANG ; Guangbiao XI ; Longmei ZHAO ; Yurong ZHANG ; Peng YUAN
Chinese Journal of Oncology 2024;46(3):256-262
Objective:To explore the efficacy and safety of Rivaroxaban in preventing catheter related thrombosis (CRT) in patients with breast cancer who are undergoing central venous catheter chemotherapy, and provide basis for making standardized prevention and treatment strategies.Methods:In this research, a prospective cohort study was adopted, and breast cancer patients who received central venous catheter chemotherapy in Sanhuan Cancer Hospital during September 2020 to March 2022 were selected as a treatment group to take the rivaroxaban anticoagulation therapy with 10 mg.po.qd for one month. The control group got no preventive anticoagulation therapy. Vascular ultrasound examination was taken to confirm the occurrence of CRT, and a chi-square test was done for comparison the disparity between the groups. Logistic regression was applied to analyze the univariate and multivariate factors for the formation of CRT.Results:In the research, a total of 235 patients were selected, and there were a total of 19 035 days of catheterization with 81 days of catheterization on average. While in the control group, the incidence of CRT was 28.0% (33/118), the incidence of CRT in the treatment group was 20.5% (24/117), the difference was no significant ( P=0.183). Subgroup analysis results showed that the peripherally inserted central catheter (PICC) was performed in 165 cases with the CRT incidence of 18.2% (30/165) and thrombosis was mostly seen around axillary vein, accounting for 63.3%. Subclavian vein catheterization was performed in 63 cases with the CRT incidence of 39.7% (25/63), and thrombosis was mostly seen around subclavian vein, accounting for 88.0% (22/25). Implantable venous access port was implanted in 7 cases around subclavian vein and internal jugular vein with the CRT incidence of 28.6% (2/7). The patients who developed CRT within 30 days after catheterization accounted for 54.4% (31/57), 22.8% (13/57) in a period during 30 days and 60 days) and 22.8% (13/57) in a period during 60 days and 180 days). The diagnosed CRT patients had been treated with rivaroxaban 15 mg.bid.po for 3 months. During the 3 months, 100.0% of the thrombosis waned, 71.9% (41/57) of the thrombosis waned within 30 days, 19.3% (11/57) in a period during 30 and 60days and 8.8% (5/57) in a period during 60 days and 90 days. Univariate and multivariate analysis indicated that the risk of CRT in subclavian vein catheterization was higher than that in PICC, respectively ( OR=2.898, 95% CI:1.386-6.056 P=0.005), and the type of catheterization was an independent factor for the formation of thrombosis. Safety analysis result showed that in the prevention of CRT, rivaroxaban treatment did not induce drug-related bleeding, liver function damage, bone marrow suppression or any other side effects. While CRT diagnosed patients were treated with anticoagulation, they kept the central venous catheter, and the infusion was smooth. These patients all finished the anti-tumor treatment as planned, and no abnormalities like new thrombosis or pulmonary embolism were observed. Conclusions:In the mid-term analysis, the proportion of Rivaroxaban in preventing anticoagulant CRT decreases, but it don't reach statistical significance. The sample size should be further increased for observation. Rivaroxaban is proved effective and very safe in the treatment of CRT, and does not affect the concurrent chemotherapy. Medical personnel should carry out the policy of "early prevention, early detection and early treatment" for CRT so as to improve the patients' quality of life.
5.The Logical Framework of Knowledge Graph Empowering Teaching and Its Practical Exploration in Medical Education
Journal of Medical Informatics 2024;45(9):96-101
Purpose/Significance To construct a knowledge graph intelligent teaching application system,and to provide data sup-port for medical universities and colleges to continuously optimize specialty construction and improve the training quality of medical and relevant specialty.Method/Process By using literature induction method,the paper systematically sorts out the current application pro-gress of knowledge graph in teaching,and builds a knowledge graph intelligent teaching application system based on Bloom's teaching cognitive model,combined with students'learning situation and underlying algorithms.Result/Conclusion Through accurate detection,content push and path planning,the system forms a dynamic closed-loop teaching feedback mechanism,which helps to improve the pre-cision teaching ability of clinical teachers and promote personalized learning of medical students.
6.Changes in blood lipid levels and influencing factors among treatment-na?ve adult male HlV/AlDS patients following BlC/FTC/TAF vs. 3TC+EFV+TDF
Xi WANG ; An LIU ; Zaicun LI ; Hongwei ZHANG ; Esther Ruojun WU ; Ying SHAO ; Jianwei LI ; Jiangzhu YE ; Wei LIU ; Lijun SUN
Chinese Medical Journal 2024;137(12):1447-1452
Background::Antiretroviral therapy (ART) was often associated with dyslipidemia among human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients. This study aimed to assess treatment-na?ve adult male patients with HIV/AIDS who initiated ART with either co-formulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) or lamivudine, efavirenz, and tenofovir disoproxil fumarate (3TC+EFV+TDF), monitoring at weeks 4, 12, 24, and 48.Methods::A case-control retrospective study was conducted. The newly diagnosed HIV-infected individuals attending the sexual transmission disease (STD)/AIDS clinic of Beijing Youan Hospital, Capital Medical University, from January to December 2021. The patients were divided into BIC/FTC/TAF group or 3TC+EFV+TDF group. High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) at different time points over 48 weeks between two groups were compared. A multivariate Cox regression model was used to identify relevant influencing factors for the population at high risk of increased LDL-C.Results::A total of 870 participants, with 510 in BIC/FTC/TAF group and 360 in 3TC+EFV+TDF group. There were no statistically significant differences in median age, baseline CD4/CD8 ratio, median body mass index (BMI) between the two groups. In both two groups, levels of TG, TC, and LDL-C were higher at 4 weeks, 12 weeks, and 24 weeks of treatment (all P <0.05), and there were no statistically significant differences at 48 weeks compared to those at baseline (all P >0.05). In addition, the differences in average changes of the level of TG, TC, HDL-C, and LDL-C from weeks 4, 12, 24, and 48 to baseline between two groups were not statistically significant (all P >0.05). Multivariate Cox proportional risk model analysis showed that initiating ART with HIV RNA ≥10 5 copies/mL (compared with <10 5 copies/mL) was associated with an increased risk of elevated LDL-C (hazard ratio = 1.26, 95% confidence interval: 1.07-1.48, P = 0.005). Conclusions::Transient elevations in blood lipid levels (TC, TG, HDL-C, and LDL-C) were observed in treatment-na?ve adult male HIV/AIDS patients with BIC/FTC/TAF at 4 weeks, 12 weeks, and 24 weeks of treatment. However, these levels did not differ significantly from baseline after 48 weeks of treatment, regardless of whether patients were in the BIC/FTC/TAF or 3TC+EFV+TDF group.
7.Mid-term analysis of prospective cohort study of rivaroxaban in preventing CRT in breast cancer
Die SANG ; Shanmin FAN ; Shiyu LI ; Jintao ZHANG ; Hengmin WANG ; Xiaohui ZHAO ; Lijun ZHENG ; Ping LIANG ; Guangbiao XI ; Longmei ZHAO ; Yurong ZHANG ; Peng YUAN
Chinese Journal of Oncology 2024;46(3):256-262
Objective:To explore the efficacy and safety of Rivaroxaban in preventing catheter related thrombosis (CRT) in patients with breast cancer who are undergoing central venous catheter chemotherapy, and provide basis for making standardized prevention and treatment strategies.Methods:In this research, a prospective cohort study was adopted, and breast cancer patients who received central venous catheter chemotherapy in Sanhuan Cancer Hospital during September 2020 to March 2022 were selected as a treatment group to take the rivaroxaban anticoagulation therapy with 10 mg.po.qd for one month. The control group got no preventive anticoagulation therapy. Vascular ultrasound examination was taken to confirm the occurrence of CRT, and a chi-square test was done for comparison the disparity between the groups. Logistic regression was applied to analyze the univariate and multivariate factors for the formation of CRT.Results:In the research, a total of 235 patients were selected, and there were a total of 19 035 days of catheterization with 81 days of catheterization on average. While in the control group, the incidence of CRT was 28.0% (33/118), the incidence of CRT in the treatment group was 20.5% (24/117), the difference was no significant ( P=0.183). Subgroup analysis results showed that the peripherally inserted central catheter (PICC) was performed in 165 cases with the CRT incidence of 18.2% (30/165) and thrombosis was mostly seen around axillary vein, accounting for 63.3%. Subclavian vein catheterization was performed in 63 cases with the CRT incidence of 39.7% (25/63), and thrombosis was mostly seen around subclavian vein, accounting for 88.0% (22/25). Implantable venous access port was implanted in 7 cases around subclavian vein and internal jugular vein with the CRT incidence of 28.6% (2/7). The patients who developed CRT within 30 days after catheterization accounted for 54.4% (31/57), 22.8% (13/57) in a period during 30 days and 60 days) and 22.8% (13/57) in a period during 60 days and 180 days). The diagnosed CRT patients had been treated with rivaroxaban 15 mg.bid.po for 3 months. During the 3 months, 100.0% of the thrombosis waned, 71.9% (41/57) of the thrombosis waned within 30 days, 19.3% (11/57) in a period during 30 and 60days and 8.8% (5/57) in a period during 60 days and 90 days. Univariate and multivariate analysis indicated that the risk of CRT in subclavian vein catheterization was higher than that in PICC, respectively ( OR=2.898, 95% CI:1.386-6.056 P=0.005), and the type of catheterization was an independent factor for the formation of thrombosis. Safety analysis result showed that in the prevention of CRT, rivaroxaban treatment did not induce drug-related bleeding, liver function damage, bone marrow suppression or any other side effects. While CRT diagnosed patients were treated with anticoagulation, they kept the central venous catheter, and the infusion was smooth. These patients all finished the anti-tumor treatment as planned, and no abnormalities like new thrombosis or pulmonary embolism were observed. Conclusions:In the mid-term analysis, the proportion of Rivaroxaban in preventing anticoagulant CRT decreases, but it don't reach statistical significance. The sample size should be further increased for observation. Rivaroxaban is proved effective and very safe in the treatment of CRT, and does not affect the concurrent chemotherapy. Medical personnel should carry out the policy of "early prevention, early detection and early treatment" for CRT so as to improve the patients' quality of life.
8.Analysis of language and influencing factors of children with speech disorder in Beijing
Jianhong WANG ; Qi XU ; Haifeng DUAN ; Lei WANG ; Bo ZHOU ; Lili ZHANG ; Xi WANG ; Lijun ZHOU ; Xueman LIU ; Lin WANG
Chinese Journal of Pediatrics 2024;62(5):438-443
Objective:To investigate the features and influencing factors of language in children with various types of speech disorders.Methods:A case-control study was carried out, 262 children with speech disorder had been diagnosed at the language-speech clinic of the Center of Children′s Healthcare, Children′s Hospital, Capital Institute of Pediatrics from January 2021 to November 2023, the children with speech sound disorder as the speech sound disorder group, the children with developmental stuttering as the stuttering group. There were 100 typically-developed children who underwent physical checkups at the Center of Healthcare during the same period as the healthy group. All children experienced a standardized evaluation of language with diagnostic receptive and expressive assessment of mandarin‐comprehensive(DREAM-C) and questionnaire, One-way ANOVA and LSD test were conducted to compare the differences in overall language, receptive language, expressive language, semantics, and syntax scores among 3 groups of children. According to the results of DREAM-C, the children with speech disorder were divided into language normal group and language delay group. Chi‐square test and multivariate Logistic regression were implemented to analyze the association between the linguistic development of children with speech disorder and potential influential factors.Results:There were 145 children in the speech sound disorder group, including 110 males and 35 females respectively, with an age of (5.9±1.0) years; 117 children in the stuttering group, including 91 males and 26 females, with an age of (5.8±1.0) years; 100 children in the healthy group, including 75 males and 25 females, with an age of (5.7±1.2) years. The variations in overall language, expressive language, and syntax scores among 3 groups of children were statistically significant (92±18 vs.96±11 vs. 98±11, 81±18 vs. 84±14 vs. 88±13, 87±16 vs. 89±11 vs. 91±10, F=5.46, 4.69, 3.68, all P<0.05). Pairwise comparison revealed that the speech sound disorder group had lower scores in overall language, expressive language, and syntactic compared to the healthy group, and the differences were statistically significant (all P<0.01) and the overall language score was lower than that of children with stuttering ( P<0.05). In terms of overall language and expressive language, there was a statistically significant difference in the incidence of language delay among the three groups of children (15.9% (23/145) vs. 20.5% (24/117) vs. 7.0% (7/100), 46.2% (67/145) vs. 39.3% (46/117) vs. 26.0% (26/100); χ2=7.93, 10.28; both P<0.05). In terms of overall language, the stuttering group took up the highest proportion. In terms of expressive language, the speech sound disorder group accounted for the highest amount. The incidence of language delay in children with speech disorder was 44.3% (116/262). Non-parent-child reading, daily screen time ≥1 hour and screen exposure before 1.5 years of age are risk factors for the development of language in children with speech disorder ( OR=1.87, 2.18, 2.01; 95% CI 1.07-3.27, 1.23-3.86, 1.17-3.45; all P<0.01). Negative family history are protective factors for the progress of language ability ( OR=0.37, 95% CI 0.17-0.81, P<0.05). Conclusions:Children with speech disorder tend to have easy access to language delay, especially in expressive language and syntax. The occurrence of language delay in children with speech disorder is tightly connected with factors such as the family medical history, parent-child reading, screen time, etc. Attention should be paid to the development of language in children who suffer from speech disorder.
9.Effects of continuous blood purification on mitochondrial function of mononuclear cells and prognosis of patients with traumatic sepsis
Zhixin LI ; Tie LYU ; Liezhou JIN ; Lyujian CHEN ; Xiaolong XI ; Lijun YING
Chinese Journal of Trauma 2024;40(11):1008-1015
Objective:To investigate the effects of continuous blood purification (CBP) on mitochondrial function of peripheral blood mononuclear cells and clinical prognosis of patients with traumatic sepsis.Methods:A prospective cohort study was used to analyze the clinical data of 90 patients with traumatic sepsis admitted to the Intensive Care Unit of Shaoxing People′s Hospital from January 2023 to June 2024. Based on standard operating procedures (SOP), patients were divided into CBP group and non-CBP group according to whether they received CBP treatment. The mitochondrial DNA (mtDNA) copy number, activity of mitochondrial respiratory chain complex V, levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-10 in the mononuclear cells on ICU admission and at 12, 24 and 48 hours after treatment were compared between the two groups. Acute physiology and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score on ICU admission and at 48 hours after treatment were detected in the two groups. The length of ICU stay, total length of hospital stay and 28-day mortality after ICU admission were compared between the two groups.Results:A total of 90 patients with traumatic sepsis were included, comprising 56 males and 34 females, aged 18-82 years [51.3(38.7, 70.6)years], with injury severity score (ISS) of 16-54 points [36.2(17.0, 53.6)points]. There were 52 patients in the CBP group and 38 in the non-CBP group. All the patients were followed up for 7-14 days [10.0(8.0, 12.0)days]. On ICU admission, the mtDNA copy number was 638.5±124.0 in the CBP group and 634.7±122.1 in the non-CBP group ( P>0.05). At 12, 24 and 48 hours after treatment, the mtDNA copy number in the CBP group was 564.2±105.6, 415.7±83.5 and 303.7±77.0 respectively, significantly lower than 622.9±120.2, 581.5±113.6, 530.7±97.8 in the non-CBP group ( P<0.05 or 0.01). At 12, 24 and 48 hours after treatment, the mtDNA copy number in both groups continued to decrease compared with that on ICU admission ( P<0.05). On ICU admission, the activity of mitochondrial respiratory chain complex Ⅴ was (74.0±26.0)pg/ml in the CBP group and (72.8±25.3)pg/ml in the non-CBP group ( P>0.05); at 12, 24 and 48 hours after treatment, it was (69.4±24.2)pg/ml, (78.3±26.8)pg/ml and (91.5±33.5)pg/ml respectively in the CBP group, significantly higher than (65.3±23.6)pg/ml, (60.7±19.4)pg/ml and (53.8±16.9)pg/ml in the non-CBP group ( P<0.05 or 0.01); at 12 hours after treatment, it was decreased in both groups compared with that on ICU admission ( P<0.05); at 24 and 48 hours after treatment, it was gradually increased in the CBP group compared with those on ICU admission and at 12 hours after treatment ( P<0.05), while in the non-CBP group, it continued to decrease ( P<0.05). The levels of TNF-α, IL-6 and IL-10 on ICU admission were (51.6±17.1)pg/ml, (174.1±57.3)pg/ml and (67.6±16.2)pg/ml respectively in the CBP group and (49.5±16.7)pg/ml, (177.8±58.7)pg/ml and (65.7±16.6)pg/ml respectively in the non-CBP group ( P>0.05). At 12, 24 and 48 hours after treatment, the levels of TNF-α in the CBP group were (43.6±15.6)pg/ml, (29.4±12.5)pg/ml and (26.2±10.6)pg/ml respectively, the IL-6 levels were (122.4±41.7)pg/ml, (90.6±33.1)pg/ml, (75.6±24.7)pg/ml respectively and the IL-10 levels were (72.6±18.1)pg/ml, (80.7±20.6)pg/ml, (86.2±22.9)pg/ml respectively, which were significantly lower than (48.8±16.2)pg/ml, (46.5±15.5)pg/ml, (40.0±14.2)pg/ml at 12 hours after treatment, (168.4±51.6)pg/ml, (131.5±42.7)pg/ml, (112.7±35.8)pg/ml at 24 hours after treatment, and (78.6±19.3)pg/ml, (91.1±23.8)pg/ml, (99.4±26.6)pg/ml at 48 hours after treatment in the non-CBP group ( P<0.05 or 0.01). At 12, 24 and 48 hours after treatment, the levels of TNF-α and IL-6 in both groups continued to decrease, while the levels of IL-10 continued to increase compared with those on ICU admission ( P<0.05). On ICU admission, the APACHE Ⅱ and SOFA scores were (20.6±10.5)points and (6.2±1.9)points in the CBP group and (21.2±11.2)points and (6.7±2.1)points in the non-CBP group ( P>0.05). At 48 hours after treatment, the APACHE Ⅱ and SOFA scores were (13.5±6.6)points and (2.7±0.6)points in the CBP group, which were significantly lower than (18.3±9.3)points and (5.3±1.5)points in the non-CBP group ( P<0.01). At 48 hours after treatment, the APACHE II and SOFA scores in both groups were significantly decreased compared with those on ICU admission ( P<0.05 or 0.01). The length of ICU stay, total length of hospital stay and 28-day mortality after ICU admission were (13.0±5.7)days, (20.4±8.6)days and 19.2% (10/52) respectively, which were significantly shorter and smaller than (17.6±6.6)days, (26.5±9.4)days and 31.6% (12/38) in the non-CBP group ( P<0.05 or 0.01). Conclusions:CBP treatment may reduce the release of mtDNA by alleviating the mitochondrial damage of the mononuclear cells in patients with traumatic sepsis so that the release of inflammatory factors and cellular apoptosis is reduced, and improve the state of cell energy metabolism and cellular immune function by increasing the activity of mitochondrial respiratory chain complex V in the mononuclear cells, and participate in the reconstruction of immune homeostasis of the body so the inflammatory state and clinical prognosis of the patients are improved.
10.Clinical applicability of the four-grade tricuspid regurgitation classification in relation to the guideline-recommended three-grade classification
Xi ZHANG ; Yuxin ZHANG ; Bijun TAN ; Ying HOU ; Liwei WEN ; Lijun YUAN ; Changyang XING
Chinese Journal of Ultrasonography 2024;33(6):475-481
Objective:To investigate the clinical applicability of the four-grade grading(G4) advocated by the academy in recent years compared with the guideline-recommended three-grade grading(G3) in functional tricuspid regurgitation (FTR).Methods:A total of 137 consecutive patients were prospectively included from outpatient and inpatient clinics at Tangdu Hospital, Air Force Medical University from May to December 2023. All patients underwent echocardiography and were graded for regurgitation based on the 2017 American Society of Echocardiography Valve Evaluation Guidelines as the reference standard. The patients with regurgitation were grouped according to the G3 based on the guidelines and the G4 advocated by the academic community in recent years, respectively. The consistency of the regurgitation grading between multi-indicators and single-indicators was analyzed using the Kappa test for both G3 and G4. The quantitative regurgitation relevant parameters were analyzed using ROC curves to evaluate the diagnostic efficacies for G4, including the vena contracta width (VCW), the area of the color flow jet (A Jet), and the radius of the PISA (R PISA). Results:The results of consistency analysis showed that the consistency of regurgitation volume (RVol) was significantly higher in the G4 multi-indicators comprehensive assessment versus the single-indicators assessment compared with the G3, with a Kappa value of 0.84 vs. 0.30. The consistency of effective regurgitant orifice area (EROA) and VCW remained unchanged, with a Kappa value of 0.76 vs. 0.89, 0.51 vs. 0.66. ROC curve analysis showed that for the G4, the area under the curve (AUC) for moderate regurgitation were 0.854, 0.993, and 0.894, respectively, while for moderate-severe regurgitation, these values were 0.899, 0.979, and 0.917, respectively.Conclusions:For FTR, the G4 currently advocated by the academic community has better consistency between single-indicators and comprehensive indicators grading than the G3 based on the guideline, which is clinically applicable; A Jet, R PISA, and VCW can be supplemented to the G4, which helps to improve the quantitative assessment system.

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