1.Exploration of Pulmonary Vascular Remodeling Improvement in Rats at Different Stages of Chronic Obstructive Pulmonary Disease by Qibai Pingfei Capsules Based on TLR4/NF-κB Signaling Pathway
Lu ZHANG ; Li FANG ; Shuyu XU ; Xue LIANG ; Jie ZHU ; Xiangli TONG ; Zegeng LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):48-56
ObjectiveTo investigate the improvement effect of Qibai Pingfei capsules on pulmonary vascular remodeling in rats at different stages of chronic obstructive pulmonary disease (COPD) and to analyze its possible mechanism of action. MethodsMale Sprague-Dawley (SD) rats were randomly divided into a normal group, an early COPD model group, an advanced COPD model group, an early-intervention high-dose group, a late-intervention high-dose group, an early-intervention low-dose group, a late-intervention low-dose group, an early-intervention pyrrolidine dithiocarbamate (PDTC) group, and a late-intervention PDTC group, with 15 rats in each group. A rat model of early COPD was constructed by using cigarette smoke combined with airway infusion using lipopolysaccharide(LPS), and a rat model of advanced COPD was constructed by using airway infusion with LPS, cigarette smoke, and hypoxia. All groups except the normal group were given LPS airway drops on days 1 and 14 of the experiment, smoked for 1 h per day, and administered the drug once a day for 40 weeks from day 15 onward. In the high- and low-dose groups, rats were given 1 g·kg-1 and 250 mg·kg-1 Qibai Pingfei capsules, respectively by gavage, and in PDTC groups, rats were given 100 mg·kg-1 of PDTC by intraperitoneal injection. The advanced COPD model group underwent 6 h of hypoxia per day in weeks 5-6. Lung function and mean pulmonary artery pressure were tested in rats. Morphologic changes in lung tissues were detected by hematoxylin-eosin(HE)staining. Collagen deposition in lung tissues was examined by Masson staining, and the levels of inflammatory factors including interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α)in lung tissues were detected by enzyme-linked immunosorbent assay (ELISA). The number of inflammatory cells in the alveolar lavage fluid of rats in each group was detected by Giemsa staining, and the protein expression of Toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88), nuclear factor-κB(NF-κB), TNF-α, vascular endothelial-cadherin(VE-cadherin), α-smooth muscle actin(α-SMA), and platelet endothelial cell adhesion molecule-1(CD31) was detected by Western blot in the lung tissues of rats. ResultsCompared with the normal group, the model group showed significantly decreased forced expiratory volume in 0.3 s (FEV0.3), forced vital capacity (FVC), and FEV0.3/FVC ratio related to lung function (P<0.05), thickening of pulmonary vasculature, increased collagen deposition in the lungs, and enhanced mean pulmonary arterial pressure and expression levels of IL-6, IL-1β, and TNF-α (P<0.05). Additionally, the model group also exhibited increased numbers of macrophages, lymphocytes, and neutrophils (P<0.05), significantly higher protein expression of TLR4, MyD88, NF-κB, TNF-α, and α-SMA (P<0.05), and significantly lower protein expression of VE-cadherin and CD31 (P<0.05). Lung function was significantly improved in the Qibai Pingfei capsules groups compared with the model group (P<0.05), with mean pulmonary arterial pressure reduced and pulmonary vascular thickening and collagen deposition in the lungs ameliorated. The Qibai Pingfei capsules groups also showed reduced expression levels of IL-6, IL-1β, and TNF-α (P<0.05) and decreased numbers of macrophages, lymphocytes, and neutrophils (P<0.05), as well as reduced protein expression of TLR4, MyD88, NF-κB, TNF-α, and α-SMA (P<0.05) and elevated protein expression of VE-cadherin and CD31 (P<0.05) in rat lung tissues. ConclusionQibai Pingfei capsules inhibits inflammatory response and endothelial-to-mesenchymal transition probably by regulating the TLR4/NF-κB signaling pathway, thus improving pulmonary vascular remodeling in COPD model rats and showing therapeutic effects in the early stage of COPD.
2.Assessment of ergonomics risk in typical upper limb operations of electricians based on RULA
Zekai LIANG ; Guanlin LI ; Shiheng ZHU ; Jiajie LI ; Qingsong CHEN
Journal of Environmental and Occupational Medicine 2025;42(3):254-259
Background A large number of power supply workers are involved in live working and are exposed to multiple risk factors for long periods of time during outdoor work, which in turn causes occupational health problems. Objective To identify potential ergonomic factors related to work-related musculoskeletal disorders (WMSDs) and estimate the ergonomic risk of electricians. Methods A total of 31 workers were randomly selected from a training base under a power supply enterprise in Guangxi, and their operation processes were recorded by video. Using the Rapid Upper Limb Assessment (RULA) method, the workers were scored by the posture of their arms, neck, and torso during operation, and the final scores were summarized to assess their risk level. Two independent samples t-tests were used to compare the differences in RULA scores. Results A total of 31 videos for mounting/dismounting insulation mask and 29 videos for breaking/connecting contact terminal were collected. The RULA score for mounting/dismounting insulation mask was 6.6 ± 0.7 (left side) and 7.0 ± 0.2 (right side), most of the workers had a score of 7 (71.0% on the left side and 96.8% on the right side), and the upper limb and overall scores on the right side were higher than those on the left side (P < 0.05). The RULA score for breaking/connecting contact terminal was 6.9 ± 0.4 (both right and left sides), most of workers had a score of 7 (89.7% on the left side and 93.1% on the right side), and the difference of the overall scores between the right and left side for this operation were not statistically significant (P > 0.05). The ergonomic risk levels for both operations were level 3 or higher. Conclusion Mounting/dismounting insulation mask and breaking/connecting contact terminal are typical upper limb operations, and have a high level of ergonomics risk, requiring effective preventive and protective measures.
3.Impact of childhood maltreatment and sleep quality on depressive symptoms among middle school students
Chinese Journal of School Health 2025;46(1):73-77
Objective:
To explore the impact of sleep quality, experience of childhood maltreatment, and their interaction on depressive symptoms among middle school students, so as to provide the reference for early intervention of depressive symptoms among middle school students.
Methods:
From September to December 2023, a questionnaire survey was conducted among 1 231 students from two secondary schools in Harbin, Heilongjiang Province by a convenient sampling method. The survey included general demographic information, Childhood Trauma Questionnaire Short Form, Pittsburgh Sleep Quality Index and Short Version of Center for Epidemiological Studies Depression Scale. The Chi square test was used to analyze the differences in depressive symptom, sleep quality and childhood maltreatment among students with different demographic characteristics. Correlation analysis was conducted using Logistic regression, and interaction analysis was performed by both additive and multiplicative interaction models.
Results:
The detection rate of depressive symptoms among middle school students was 22.7%, and the rate for high school students (35.2%) was significantly higher than that for middle school students (17.0%) ( χ 2=50.35, P <0.01). The detection rates of depressive symptoms among middle school students with a history of childhood maltreatment and poor sleep quality were 45.8% and 44.0%, respectively. Multivariate Logistic regression analysis showed that compared to students without a history of childhood maltreatment, students with a history of childhood maltreatment had a higher risk of depressive symptoms ( OR =4.49,95% CI =3.31~ 6.09 , P <0.01);students with poor sleep quality had a higher risk of depressive symptoms than students with good sleep quality ( OR = 5.99,95% CI =4.37~8.22, P <0.01).The interaction results showed that the presence of childhood maltreatment and poor sleep quality had an additive interaction on the occurrence of depression in middle school students. Compared with students without childhood maltreatment and having good sleep quality, students with childhood maltreatment and poor sleep quality had a 22.49 times higher risk of developing depression ( OR =22.49,95% CI =14.22~35.59, P <0.01).
Conclusion
Depressive symptoms among middle school students are associated with childhood maltreatment and poor sleep quality, and there is an additive interaction between childhood maltreatment and poor sleep quality on the impact of depressive symptoms.
4.Analysis of clinical infection characteristics of multidrug-resistant organisms in hospitalized patients in a tertiary sentinel hospital in Shanghai from 2021 to 2023
Qi MAO ; Tenglong ZHAO ; Xihong LYU ; Zhiyuan GU ; Bin CHEN ; Lidi ZHAO ; Xifeng LI ; Xing ZHANG ; Liang TIAN ; Renyi ZHU
Shanghai Journal of Preventive Medicine 2025;37(2):156-159
ObjectiveTo understand the infection characteristics of multidrug-resistant organisms (MDROs) in hospitalized patients in a tertiary sentinel hospital in Shanghai, so as to provide an evidence for the development of targeted prevention and control measures. MethodsData of MDROs strains and corresponding medical records of some hospitalized patients in a hospital in Shanghai from 2021 to 2023 were collected, together with an analysis of the basic information, clinical treatment, underlying diseases and sources of sample collection. ResultsA total of 134 strains of MDROs isolated from hospitalized patients in this hospital were collected from 2021 to 2023 , including 63 strains of methicillin-resistant Staphylococcus aureus (MRSA), 57 strains of carbapenem-resistant Acinetobacter baumannii (CRAB), and 14 strains of carbapenem-resistant Klebsiella pneumoniae (CRKP). Of the 134 strains, 30 strains were found in 2021, 47 strains in 2022 and 57 strains in 2023. The male-to-female ratio of patients was 2.05∶1, with the highest percentage (70.90%) in the age group of 60‒<90 years. The primary diagnosis was mainly respiratory disease, with lung and respiratory tract as the cheif infection sites. There was no statistically significant difference in the distribution of strains between different genders and infection sites (P>0.05). However, the differences in the distribution of strains between different ages and primary diagnosis were statistically significant (P<0.05). Patients who were admitted to the intensive care unit (ICU), had urinary tract intubation, were not artery or vein intubated, were not on a ventilator, were not using immunosuppresants or hormones, and were not applying radiotherapy or chemotherapy were in the majority. There was no statistically significant difference in the distribution of strains for whether received radiotherapy or chemotherapy or not (P>0.05), while the differences in the distribution of strains with ICU admission history, urinary tract intubation, artery or vein intubation, ventilator use, and immunosuppresants or hormones use or not were statistically significant (all P<0.05). The type of specimen was mainly sputum, the hospitalized ward was mainly comprehensive ICU, the sampling time was mainly in the first quarter throughout the year, the number of underlying diseases was mainly between 1 to 2 kinds, the application of antibiotics ≥4 kinds, and those who didn’t receive any surgery recently accounted for the most. There were statistically significant differences in the distribution of strains between different specimen types, wards occupied and history of ICU stay (P<0.05), but no statistically significant difference in the distribution of strains between different sampling times, number of underlying diseases and types of antibiotics applied (P>0.05). ConclusionThe situation of prevention and control on MDROs in this hospital is still serious. Focus should be placed on high-risk factors’ and infection monitoring and preventive measures should be strengthened to reduce the incidence rate of MDROs infection.
5.Distribution of Traditional Chinese Medicine Syndrome Elements in Different Risk Populations of Heart Failure Complicated with Type 2 Diabetes: A Retrospective Study Based on Nomogram Model and Factor Analysis
Tingting LI ; Zhipeng YAN ; Yajie FAN ; Wenxiu LI ; Wenyu SHANG ; Yongchun LIANG ; Yiming ZUO ; Yuxin KANG ; Boyu ZHU ; Junping ZHANG
Journal of Traditional Chinese Medicine 2025;66(11):1140-1146
ObjectiveTo analyze the distribution characteristics of traditional Chinese medicine (TCM) syndrome elements in different risk populations of heart failure complicated with type 2 diabetes. MethodsClinical data of 675 type 2 diabetes patients were retrospectively collected. Lasso-multivariate Logistic regression was used to construct a clinical prediction nomogram model. Based on this, 441 non-heart failure patients were divided into a low-risk group (325 cases) and a high-risk group (116 cases) according to the median risk score of heart failure complicated with type 2 diabetes. TCM diagnostic information (four diagnostic methods) was collected for both groups, and factor analysis was applied to summarize the distribution of TCM syndrome elements in different risk populations. ResultsLasso-multivariate Logistic regression analysis identified age, disease duration, coronary heart disease, old myocardial infarction, arrhythmia, absolute neutrophil count, activated partial thromboplastin time, and α-hydroxybutyrate dehydrogenase as independent risk factors for heart failure complicated with type 2 diabetes. These were used as final predictive factors to construct the nomogram model. Model validation results showed that the area under the curve (AUC) of the receiver operating characteristic (ROC) curve for the modeling group and validation group were 0.934 and 0.935, respectively. The Hosmer-Lemeshow test (modeling group P = 0.996, validation group P = 0.121) indicated good model discrimination. Decision curve analysis showed that the curves for All and None crossed in the upper right corner, indicating high clinical utility. The low-risk and high-risk groups each obtained 14 common factors. Preliminary analysis revealed that the main disease elements in the low-risk group were qi deficiency (175 cases, 53.85%), dampness (118 cases, 36.31%), and heat (118 cases, 36.31%), with the primary locations in the spleen (125 cases, 38.46%) and lungs (99 cases, 30.46%). In the high-risk group, the main disease elements were yang deficiency (73 cases, 62.93%), blood stasis (68 cases, 58.62%), and heat (49 cases, 42.24%), with the primary locations in the kidney (84 cases, 72.41%) and heart (70 cases, 60.34%). ConclusionThe overall disease characteristics in different risk populations of type 2 diabetes patients with heart failure are a combination of deficiency and excess, with deficiency being predominant. Deficiency and heat are present throughout. The low-risk population mainly shows qi deficiency with dampness and heat, related to the spleen and lungs. The high-risk population shows yang deficiency with blood stasis and heat, related to the kidneys and heart.
6.Effects of transcranial alternating current stimulation combined with sertraline on cognitive function in patients with depressive disorder
Dan LI ; Zhong XIA ; Wenli ZHU ; Dandan LIANG ; Wenwen MIAO ; Chuanfu SONG
Sichuan Mental Health 2025;38(3):204-210
BackgroundCognitive function is closely related to an individual's quality of life and social functioning, with approximately 20%~35% of patients with depressive disorder experiencing some degree of cognitive impairment even after clinical symptom remission. Existing evidence suggests that tACS can improve specific cognitive domains, such as memory function, while its effects on other cognitive dimensions, such as executive functioning, attention, and information processing speed, remain unclear. ObjectiveTo explore the effects of tACS on the multidimensional cognitive functions and emotional problems of patients with depressive disorder, thus to provide references for the treatment of depressive disorder. MethodsForty-nine patients with depressive disorder who were hospitalized in the Fourth People's Hospital of Wuhu from November 2022 to October 2024 and met the diagnostic criteria for depressive disorder outlined in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), were selected as study participants. Subjects were randomly divided into study group (n=23) and control group (n=26) based on Microsoft Excel. Both groups received sertraline treatment. The initial dose was 50 mg/day, which gradually titrated upward based on individual variability, drug tolerance, and therapeutic response, with a maintenance dose ranging from 100 to 200 mg/day. In addition, the study group underwent tACS therapy for 4 weeks, with 5 sessions per week, each lasting 20 minutes. The control group received sham stimulation, in which the stimulus was interrupted after the first 30 seconds. At baseline, the 4th week, and the 12th week of treatment, patients were assessed using the Hamilton Depression Scale-17 item (HAMD-17), Hamilton Anxiety Scale (HAMA), and MATRICS Consensus Cognitive Battery (MCCB). ResultsRepeated measures analysis of variance indicated that both the time effect and the time×group interaction effect for HAMD-17 scores were statistically significant between the two groups (F=260.437, 25.309, P<0.01). At week 12 of treatment, the HAMD-17 score in the study group was lower than that in the control group (t=4.236, P<0.01). For HAMA scores, the time effect, group effect, and time×group interaction effect were all statistically significant between the two groups (F=248.082, 4.506, 9.500, P<0.05 or 0.01). At weeks 4 and 12, study group reported lower HAMA scores compared with control group (t=4.580, 2.608, P<0.05 or 0.01). Regarding the MCCB scores for attention/vigilance, verbal learning, and overall composite, the time effect, group effect, and time×group interaction effect were all statistically significant between the two groups (F=70.331, 27.882, 51.679, 5.560, 10.948, 7.860, 8.490, 3.874, 5.025, P<0.05 or 0.01). After intervention, the study group showed significantly higher MCCB scores for attention/vigilance, verbal learning, and overall composite at both week 4 (t=-2.149, -3.530, -2.740, P<0.05) and week 12 (t=-3.534, -3.576, -3.838, P<0.01) when compared to the control group. ConclusionThe combined tACS and sertraline therapy may demonstrate superior efficacy to pharmacotherapy alone in the short term for improving attention/vigilance, verbal learning, overall cognitive function, and anxiety symptoms in patients with depressive disorders. Based on the 12-week outcomes, the combined tACS and sertraline therapy not only sustaine its previously observed advantages in improving cognitive domains and anxiety symptoms, but also demonstrate potentially superior efficacy over monotherapy in alleviating depressive symptoms. [Fund by Clinical Medical Research Transformation Special Project of Anhui Province (number, 202204295107020065)]
7.Factors influencing carbapenem-resistant gram-negative bacillus infection in elderly patients in the intensive care unit of a general hospital in Yangpu District, Shanghai, 2019‒2023
Wen ZHU ; Qingfeng SHI ; Yi LIANG ; Junping YU ; Yunxia LI ; Chao WENG ; Renyi ZHU
Shanghai Journal of Preventive Medicine 2025;37(6):467-475
ObjectiveTo analyze the characteristics and influencing factors of elderly hospitalized patients with carbapenem-resistant gram-negative bacillus (CRO) infection in the intensive care unit (ICU) of a gradeⅡ level A general hospital in Yangpu District of Shanghai, and to provide scientific basis for the prevention and control of hospital-acquired CRO infection in such hospitals. MethodsThe clinical data of elderly ICU patients (age ≥60 years) from January 2019 to December 2023 were retrospectively collected. A total of 122 cases with hospital-acquired CRO infection were used as the case group, and a total of 68 cases with carbapenem-sensitive gram-negative (CSO) infection were used as the control group. The clinical characteristics of the two groups were analyzed, and univariate analysis and logistic regression analysis were performed for screening for possible influencing factors on hospital-acquired CRO infection. ResultsThe main pathogens of CRO infection were carbapenem-resistant Acinetobacter baumannii (CRAB) (53 cases, 43.44%) and carbapenem-resistant Klebsiella pneumoniae (CRKP) (46 cases, 37.70%), and 17 patients (13.93%) had more than two types of CRO infection. Among the CRO infection, the main sites were lower respiratory tract infection (58 cases, 47.54%), ventilator-associated pneumonia (21 cases, 17.21%), and catheter-associated urinary tract infections (16 cases, 13.11%). The incidence rate of poor prognosis was higher in the CRO infection group (54.10%) than that in the CSO infection group (36.76%) (P=0.021). The results of univariate analysis showed that male, history of hospitalization within three months, chronic respiratory disease, hypoproteinemia, anemia, and history of invasive procedures prior to infection, including indwelling central venous catheter, invasive mechanical ventilation, urinary catheter, gastric tube placement and parenteral nutrition, in addition, heparin anticoagulation, the use of broad-spectrum penicillin, third-generation cephalosporins, fluoroquinolones, carbapenems, carbapenems combined with fluoroquinolones, carbapenems combined with glycopeptides, use of ≥3 antibiotics and long time of antibiotic use prior to infection were all associated with the CRO infection (P<0.05). The results of logistic regression analysis showed that use of carbapenems (OR=7.739, 95%CI: 2.226‒26.911), ≥3 types of antibiotics (OR=6.307, 95%CI: 1.674‒23.754), invasive mechanical ventilation (OR=4.082, 95%CI: 1.795‒9.281), urinary catheter (OR=3.554, 95%CI: 1.074‒11.758), and comorbid hypoproteinemia (OR=4.741, 95%CI: 2.039‒11.022) and diabetes (OR=3.245, 95%CI: 1.344‒7.839) were positively correlated with the risk of CRO infection. ConclusionConcurrent use of carbapenems with multiple other antibiotics, as well as the use of invasive mechanical ventilation, urinary catheter, and comorbid hypoproteinemia and diabetes, may be associated with an increased influencing of CRO infection. More attention should be paid to the prevention and control of infection in elderly patients with the above-mentioned risk factors, and active screening of drug-resistant bacteria should be strengthened. Besides, the rational use of broad-spectrum antibiotics such as carbapenems, avoiding unnecessary invasive operations, and paying attention to patient nutrition and blood glucose control all can reduce the incidence of CRO infection and help to improve clinical outcomes.
8.Latest research and prospect of CD47 in kidney transplantation
Yuxiang CHEN ; Zhuocheng LI ; Liang GAO ; Xuyuan ZHU ; Yu ZHANG ; Tao LI ; Hongtao JIANG
Organ Transplantation 2024;15(2):282-288
CD47 is a transmembrane protein widely expressed on cell surface, which is considered as a key molecule for immune escape. With an increasing number of related studies, the role of CD47 and its ligands in immunomodulatory effects has been gradually understood. Recent studies have investigated the role of CD47 in ischemia-reperfusion injury of allogenetic kidney transplantation, rejection and xenotransplantation. Nevertheless, the specific role and the key mechanism remain elusive. In this article, the structure and function of CD47, common CD47 ligands, the relationship between CD47 and kidney transplantation, and the application of CD47 in kidney transplantation were reviewed, the latest research progress of CD47 in kidney transplantation was summarized, and the limitations of current research and subsequent research direction were analyzed, aiming to provide reference for subsequent application of CD47 in allogeneic and kidney xenotransplantation.
9.Application of two different methods of visual acuity assessment for myopia screening among lower grade elementary school students
LIANG Li, XU Shaojun, ZHU Yi, XU Xing, ZHAO Mengya, WEN Yuechun, TAO Fangbiao
Chinese Journal of School Health 2024;45(2):273-276
Objective:
To explore two visual acuity standards for examining uncorrected visual acuity (UCVA) to define poor vision in lower grade elementary school students, and to compare the difference of screening myopia rates when combined with non cycloplegic auto refraction (NCAR), so as to provide a scientific basis for standardizing UCVA examination methods using CAR as the gold standard of authenticity and reliability.
Methods:
From March 22nd to April 9th, 2023, a total of 549 first and second grade students aged 7-8 years from a primary school in Hefei City were selected for the study by convenient cluster sampling method. Two methods were employed for UCVA examination:the first method involved charts where the student could not make mistakes in identifying at least half of the characters per line (V1), and the second method used charts with character sizes ranging from 4.0 -4.5, 4.6-5.0 and 5.1-5.3, without allowing 1, 2 and 3 errors per line (V2). While NCAR was performed, then 187 students underwent CAR examination. Paired Wilcoxon rank-sum test and McNemar test were used to compare the differences between V1 and V2 methods in defining poor vision and screening myopia rates. Using CAR as the gold standard, the authenticity and reliability of defining screening myopia rates through the combination of V1 and V2 methods along with NCAR were evaluated.
Results:
The UCVA examination results for V1 and V2 showed statistically significant differences in both the right eye [5.0(4.9,5.0), 4.9(4.8,5.0)] and the left eye [ 5.0 (4.9,5.0), 4.9(4.8,5.0)] ( Z=-13.95, -13.34, P <0.01). The detection rates of poor vision for the right eye were 43.53% for V1 and 63.21% for V2, and the left eye with 44.08% for V1 and 62.11% for V2, with statistically significant differences ( χ 2= 106.01 , 95.09, P <0.01). When screening myopia rates were assessed for UCNA methods combined with NCAR, the right eye rates were 21.49% for V1 and 24.59% for V2, and the left eye rates were 21.31% for V1 and 23.13% for V2, with statistically significant differences ( χ 2=15.06, 8.10, P <0.01). Using CAR as the gold standard, the detection rates in the right eye and left eye were 16.58 % and 17.11%, respectively. The Youden indices for defining screening myopia in the right eye were 0.80 for V1 and 0.79 for V2, and the left eye with 0.85 for V1 and 0.83 for V2. The agreement rates for the right eye were 91.98 % for V1 and 89.30% for V2, and the left eye with 94.12% for V1 and 91.98% for V2. The Kappa values for the right eye were 0.73 for V1 and 0.67 for V2, and the left eye with 0.81 for V1 and 0.75 for V2.
Conclusions
Authenticity and reliability of two UCVA examination methods combined with NCAR in defining screening myopia are higher in V1 than V2 methods. It is recommended to unify the visual acuity examination methods by requiring the correct identification of more than half of the total number of visual markers in a row.
10. Mechanism of levosimendan in treating hypoxic pulmonary hypertension based on network pharmacology and molecular docking technology
Xiao-Dan ZHANG ; Yu-Liang XIE ; Meng-Dan GAO ; Ao-Xue YUAN ; Han-Fei LI ; Tian-Tian ZHU ; Xiao-Dan ZHANG ; Yu-Liang XIE ; Meng-Dan GAO ; Ao-Xue YUAN ; Han-Fei LI ; Tian-Tian ZHU ; Xiao-Dan ZHANG ; Yu-Liang XIE ; Meng-Dan GAO ; Ao-Xue YUAN ; Han-Fei LI ; Tian-Tian ZHU
Chinese Pharmacological Bulletin 2024;40(3):565-573
Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.


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