1.Screening of biomarkers for fibromyalgia syndrome and analysis of immune infiltration
Yani LIU ; Jinghuan YANG ; Huihui LU ; Yufang YI ; Zhixiang LI ; Yangfu OU ; Jingli WU ; Bing WEI
Chinese Journal of Tissue Engineering Research 2025;29(5):1091-1100
BACKGROUND:Fibromyalgia syndrome,as a common rheumatic disease,is related to central sensitization and immune abnormalities.However,the specific mechanism has not been elucidated,and there is a lack of specific diagnostic markers.Exploring the possible pathogenesis of this disease has important clinical significance. OBJECTIVE:To screen the potential diagnostic marker genes of fibromyalgia syndrome and analyze the possible immune infiltration characteristics based on bioinformatics methods,such as weighted gene co-expression network analysis(WGCNA),and machine learning. METHODS:Gene expression profiles in peripheral serum of fibromyalgia syndrome patients and healthy controls were obtained from the gene expression omnibus(GEO)database.The differentially co-expressed genes were screened in the expression profile by differential analysis and WGCNA analysis.Least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE)machine learning algorithm were further used to identify hub biomarkers,and draw receiver operating characteristic curve(ROC)to evaluate the accuracy of diagnosing fibromyalgia syndrome.Finally,single sample gene set enrichment analysis(ssGSEA)and gene set enrichment analysis(GSEA)were used to evaluate the immune cell infiltration and pathway enrichment in patients with fibromyalgia syndrome. RESULTS AND CONCLUSION:Eight down-regulated differentially expressed genes(DEGs)were obtained after differential analysis of the GSE67311 dataset according to the conditions of log2|(FC)|>0 and P<0.05.After WGCNA analysis,497 genes were included in the module(MEdarkviolet)with the highest positive correlation(r=0.22,P=0.04),and 19 genes were included in the module(MEsalmon2)with the highest negative correlation(r=-0.41,P=6×10-5).After intersecting DEGs and the module genes of WGCNA,seven genes were obtained.Four genes were screened out by LASSO regression algorithm and five genes were screened out by SVM-RFE machine learning algorithm.After the intersection of the two,three core genes were identified,which were germinal center associated signaling and motility like,integrin beta-8,and carboxypeptidase A3.The areas under the ROC curve of the three core genes were 0.744,0.739,and 0.734,respectively,indicating that they have good diagnostic value and can be used as biomarkers for fibromyalgia syndrome.The results of immune infiltration analysis showed that memory B cells,CD56 bright NK cells,and mast cells were significantly down-regulated in patients with fibromyalgia syndrome compared with the control group(P<0.05),and were significantly positively correlated with the above three biomarkers(P<0.05).The enrichment analysis suggested that there were nine fibromyalgia syndrome enrichment pathways,mainly related to olfactory transduction pathway,neuroactive ligand-receptor interaction,and infection pathway.The above results showed that the occurrence and development of fibromyalgia syndrome are related to the involvement of multiple genes,abnormal immune regulation,and multiple pathways imbalance.However,the interactions between these genes and immune cells,as well as their relationships with various pathways need to be further investigated.
2.Research on multi antigen extended matching transfusion in RhCE alloantibody positive patients with blood diseases
Pin YI ; Mingming WANG ; Yi ZHU ; Xintang DANG ; Ziyu OU ; Fan WU ; Chaopeng SHAO ; Changlin WU
Chinese Journal of Blood Transfusion 2025;38(5):678-683
Objective: To analyze the changes in homologous immunity after RhCE-matched transfusion in positive patients with RhCE blood group antibodies, and to provide precise transfusion strategies for chronic anemia patients. Methods: Patients with chronic anemia in our hospital from January 2020 to March 2024 (continuously receiving blood transfusions for more than 6 months) were enrolled, and 63 cases of unexpected antibody screening positive and identified as RhCE blood group antibodies were selected as the research subjects. The changes in unexpected antibody yield rate after ABO and RhCcDEe isotype blood transfusion were observed. Patients with MNS, Kidd, or Lewis blood group antibodies were screened for corresponding negative donors using monoclonal antibodies for extended typing transfusion based on RhCcEe typing, and the changes in unexpected antibody yield rate after transfusion were observed. Blood group genotyping was performed when serological techniques failed to resolve discrepancies or detect abnormal antigen expression. Results: After RhCcDEe-matched transfusions, RhCE antibodies disappeared in 62 patients, while 1 patient developed anti-Ce. The latter did not develop blood type isotype immunity after receiving RhccEE donor blood. Among the 62 patients, 9 developed unexpected antibodies against other systems: anti-M (4 cases), anti-Mur (2), anti-S (1), anti-Jka (1), and anti-Lea (1). No additional alloimmunization occurred after extended antigen-matched transfusions. A patient with serologically weak e phenotype was genotyped as DCe/DcE, with gene sequencing revealing an 827C>A mutation in exon 6 of the RHCE gene, forming the RHCE
01.31 allele. Conclusion: Precise transfusion strategies incorporating RhCE, MNS, Kidd, and Lewis blood group antigen typing can reduce the probability of blood group homologous immunity. RhCE complex antibodies and RhCE variants pose difficulties for clinical RhCE typing transfusion, which can be addressed through cross-matching and genetic analysis.
3.Clinical application of exempting anti-D monitoring in pregnant women with Asian-type DEL
Pin YI ; Ziyu OU ; Xiaoxiao SUN ; Mingming WANG ; Changlin WU ; Chaopeng SHAO
Chinese Journal of Blood Transfusion 2025;38(6):766-771
Objective: To evaluate the feasibility of exempting Asian-type DEL pregnant women from anti-D monitoring and RhD immunoglobulin prophylaxis injections by comparing and analyzing the clinical incidence of anti-D alloimmunization between Asian-type DEL pregnant women and true RhD-negative pregnant women. Methods: A total of 165 pregnant women who were initially screened as RhD negative by the saline method and received medical treatment in our hospital from December 2022 to August 2024 were collected as the research subjects. Absorption and elution tests, DEL genotyping, and gene sequencing were used to divide the pregnant women into the Asian-type DEL group and the true negative group. After obtaining informed consent, the following clinical management plan was implemented for pregnant women with Asian-type DEL: exemption from routine anti-D antibody detection, exemption from RhD immunoglobulin prophylaxis, and transfusion of RhD-positive red blood cells. Blood samples of newborns were sent for examination of hemolytic disease of the fetus and newborn (HDFN). The routine management plan was implemented for true negative pregnant women. The incidence of alloimmunization and HDFN was comparatively analyzed between the two groups. Results: Among 165 initially screened RhD negative pregnant women, serological testing and genotyping confirmed 42 as Asian-type DEL, 9 as D variant, and 114 as true negative. Among 42 pregnant women with Asian-type DEL, 3 cases tested positive for HDFN due to receiving RhD immunoglobulin prophylaxis injection. The remaining 39 cases were exempted from anti-D testing after being fully informed of the risk, and did not receive RhD immunoglobulin prophylaxis. The HDFN tests were all negative. In the true negative group, anti-D antibodies were detected in 20 cases, of which 6 cases tested positive for HDFN. A pregnant woman with Asian -type DEL did not show RhD homologous immune response after receiving 2 units of RhD positive red blood cells. Statistical analysis revealed a significantly lower risk of anti-D alloimmunization in Asian-type DEL carriers compared to true D-negative pregnant women (P<0.05). Conclusion: Pregnant women with Asian-type DEL can be exempted from routine anti-D antibody testing and do not require routine RhD immunoglobulin prophylaxis injections.
4.Relationship between stressors and job burnout: Moderating role of job well-being
Jie WU ; Fengmin CHENG ; Ruotong YI ; Weiqian YU ; Chunyan LIU ; Mengyu OU
Journal of Environmental and Occupational Medicine 2025;42(7):833-839
Background Enhancing the sense of honor and belonging among medical staff is a key component of establishing a modern hospital management system. Compared to medical staff at general hospitals, medical staff at oncology hospitals are more prone to job burnout, yet few studies in China have focused on job burnout among employees in oncology hospitals. Objective To propose a hypothetical model in which job well-being moderates the relationship between stressors and occupational burnout, to explore how stressors influence burnout and potential moderating role of job well-being, and to provide better understanding of job burnout and motivate employees based on the double-edge sword effect of stressors. Methods A cross-sectional survey was conducted in May 2022 at a tertiary oncology specialty hospital in Chongqing, China. A total of 1 898 medical staff were recruited. Data were collectedthrough four scales including a general information questionnaire, Maslach Burnout Inventory-Human Service Survey, Work Stressor Scale, and Occupational Well-being Scale for Medical Staff. Independent sample t-tests and one-way ANOVA were used for univariate comparisons of job burnout. Pearson correlation analysis was employed to examine the relationships between job burnout, stressors, and job well-being. Hierarchical linear regression was conducted to identify factors influencing job burnout and to examine potential moderating role of job well-being in the relationship between stressors and job burnout. Results A total of 2 123 questionnaires were distributed, with 1 898 valid responses, yielding an effective response rate of 89.4%. The prevalence of job burnout was 60.1%. The correlation coefficient was 0.717 (P<0.001) between stressors and burnout, −0.784 (P<0.05) between job well-being and burnout, and −0.744 (P<0.001) between stressors and job well-being. The quadratic stressors showed a statistically significant effect on burnout (β=0.404, P<0.01). Job well-being positively moderated the relationship between the linear stressors and burnout (β=1.289, P<0.001) and negatively moderated the relationship between the quadratic stressors and job burnout (β=−0.571, P<0.01), explaining 7.1% of the variance. Conclusion Job burnout prevalence is relatively high among employees in oncology hospitals. There is a curvilinear relationship between stressors and job burnout, with job well-being moderating this relationship. From a practical perspective, it is recommended to establish a tiered stress alert system to monitor employees’ stress levels and prevent prolonged exposure to high-pressure conditions. Additionally, improving employees’ job well-being through institutional incentives and developmental support can enhance its moderating role in mitigating the adverse effects of stressors on job burnout. Meanwhile, fostering coordinated responses between organizations and individuals is crucial for strengthening mental health management systems, thereby supporting a healthy, stable, and sustainable development of the healthcare workforce.
5.USP51/GRP78/ABCB1 axis confers chemoresistance through decreasing doxorubicin accumulation in triple-negative breast cancer cells.
Yang OU ; Kun ZHANG ; Qiuying SHUAI ; Chenyang WANG ; Huayu HU ; Lixia CAO ; Chunchun QI ; Min GUO ; Zhaoxian LI ; Jie SHI ; Yuxin LIU ; Siyu ZUO ; Xiao CHEN ; Yanjing WANG ; Mengdan FENG ; Hang WANG ; Peiqing SUN ; Yi SHI ; Guang YANG ; Shuang YANG
Acta Pharmaceutica Sinica B 2025;15(5):2593-2611
Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.
6.Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial.
Xin-Yun HUANG ; Ou-Ping LIAO ; Shu-Yun JIANG ; Ji-Ming TAO ; Yang LI ; Xiao-Ying LU ; Yi-Ying LI ; Ci WANG ; Jing LI ; Xiao-Peng MA
Journal of Integrative Medicine 2025;23(1):15-24
BACKGROUND:
China is seeing a growing demand for rehabilitation treatments for post-stroke upper limb spastic paresis (PSSP-UL). Although acupuncture is known to be effective for PSSP-UL, there is room to enhance its efficacy.
OBJECTIVE:
This study explored a semi-personalized acupuncture approach for PSSP-UL that used three-dimensional kinematic analysis (3DKA) results to select additional acupoints, and investigated the feasibility, efficacy and safety of this approach.
DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS:
This single-blind, single-center, randomized, controlled trial involved 74 participants who experienced a first-ever ischemic or hemorrhagic stroke with spastic upper limb paresis. The participants were then randomly assigned to the intervention group or the control group in a 1:1 ratio. Both groups received conventional treatments and acupuncture treatment 5 days a week for 4 weeks. The main acupoints in both groups were the same, while participants in the intervention group received additional acupoints selected on the basis of 3DKA results. Follow-up assessments were conducted for 8 weeks after the treatment.
MAIN OUTCOME MEASURES:
The primary outcome was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) response rate (≥ 6-point change) at week 4. Secondary outcomes included changes in motor function (FMA-UE), Brunnstrom recovery stage (BRS), manual muscle test (MMT), spasticity (Modified Ashworth Scale, MAS), and activities of daily life (Modified Barthel Index, MBI) at week 4 and week 12.
RESULTS:
Sixty-four participants completed the trial and underwent analyses. Compared with control group, the intervention group exhibited a significantly higher FMA-UE response rate at week 4 (χ2 = 5.479, P = 0.019) and greater improvements in FMA-UE at both week 4 and week 12 (both P < 0.001). The intervention group also showed bigger improvements from baseline in the MMT grades for shoulder adduction and elbow flexion at weeks 4 and 12 as well as thumb adduction at week 4 (P = 0.007, P = 0.049, P = 0.019, P = 0.008, P = 0.029, respectively). The intervention group showed a better change in the MBI at both week 4 and week 12 (P = 0.004 and P = 0.010, respectively). Although the intervention group had a higher BRS for the hand at week 12 (P = 0.041), no intergroup differences were observed at week 4 (all P > 0.05). The two groups showed no differences in MAS grades as well as in BRS for the arm at weeks 4 and 12 (all P > 0.05).
CONCLUSION:
Semi-personalized acupuncture prescription based on 3DKA results significantly improved motor function, muscle strength, and activities of daily living in patients with PSSP-UL.
TRIAL REGISTRATION
Chinese Clinical Trial Registry ChiCTR2200056216. Please cite this article as: Huang XY, Liao OP, Jiang SY, Tao JM, Li Y, Lu XY, Li YY, Wang C, Li J, Ma XP. Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial. J Integr Med. 2025; 23(1): 15-24.
Humans
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Male
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Female
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Middle Aged
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Acupuncture Points
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Upper Extremity/physiopathology*
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Biomechanical Phenomena
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Single-Blind Method
;
Aged
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Stroke/therapy*
;
Acupuncture Therapy/methods*
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Stroke Rehabilitation/methods*
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Adult
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Muscle Spasticity/therapy*
;
Paresis/physiopathology*
;
Treatment Outcome
7.Generalized Functional Linear Models: Efficient Modeling for High-dimensional Correlated Mixture Exposures.
Bing Song ZHANG ; Hai Bin YU ; Xin PENG ; Hai Yi YAN ; Si Ran LI ; Shutong LUO ; Hui Zi WEIREN ; Zhu Jiang ZHOU ; Ya Lin KUANG ; Yi Huan ZHENG ; Chu Lan OU ; Lin Hua LIU ; Yuehua HU ; Jin Dong NI
Biomedical and Environmental Sciences 2025;38(8):961-976
OBJECTIVE:
Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects.
METHODS:
We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies.
RESULTS:
We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity.
CONCLUSION
GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans
;
Environmental Exposure/analysis*
;
Linear Models
;
Nutrition Surveys
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Environmental Pollutants
;
Body Mass Index
8.Observation on the Clinical Efficacy of Modified Xuefu Zhuyu Decoction Combined with Acupoint Application for Patients with Angina Pectoris in Coronary Heart Disease
Xiao-Hong OU ; Jin-Yi LEI ; Yu XIA ; Rong LI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(6):1409-1415
Objective To explore the clinical efficacy of modified Xuefu Zhuyu Decoction combined with acupoint application for the treatment of patients with stable angina pectoris in coronary heart disease(SAP-CHD),and to evaluate its clinical value for the treatment of SAP-CHD.Methods A total of 92 patients with SAP-CHD of heart-blood stasis and obstruction complicated with qi deficiency type were randomly divided into control group and observation group,with 46 cases in each group.The control group was treated with conventional western medicine alone,and the observation group was treated with modified Xuefu Zhuyu Decoction combined with acupoint application on the basis of treatment for the control group.The two groups were treated for 4 weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,Pittsburgh Sleep Quality Index(PSQI)scores,cardiac function indicators of left ventricular ejection fraction(LVEF),left ventricular end-systolic diameter(LVESD)and left ventricular end-diastolic diameter(LVEDD),and frequency and duration of angina pectoris in the two groups before and after treatment were observed.After treatment,the TCM syndrome efficacy in the two groups was evaluated.Results(1)After 4 weeks of treatment,the total effective rate of TCM syndrome efficacy in the observation group was 91.30%(42/46),and that of the control group was 76.09%(35/46).The intergroup comparison(tested by chi-square test)showed that the TCM syndrome efficacy in the observation group was significantly superior to that in the control group(P<0.05).(2)After treatment,the scores of TCM syndromes in the two groups were decreased compared with those before treatment(P<0.05),and the decrease in the observation group was more significant than that in the control group(P<0.05).(3)After treatment,the PSQI scores of sleep quality in the two groups were lower than those before treatment(P<0.05),and the decrease of PSQI score in the observation group was significantly superior to that in the control group after treatment(P<0.05).(4)In terms of cardiac function,LVEF in the two groups after treatment was higher than that before treatment(P<0.05),LVESD and LVEDD were lower than those before treatment(P<0.05).The increase of LVEF and the decrease of LVESD and LVEDD in the observation group were significantly superior to those in the control group after treatment(P<0.05).(5)After treatment,the frequency and duration of angina pectoris in the two groups were improved compared with those before treatment(P<0.05),and the improvement in the frequency and duration of angina pectoris in the observation group was superior to that in the control group(P<0.05).Conclusion On the basis of conventional western medicine treatment,modified Xuefu Zhuyu Decoction combined with acupoint application exerts certain clinical effect for the treatment of patients with stable angina pectoris in coronary heart disease.The combined therapy is effective on improving the cardiac function and sleep quality of the patients,reducing the attack of angina pectoris and shortening the duration of angina pectoris,with stronger efficacy than that of conventional western medicine alone.
9.Anatomical principal variations of the human pelvic ring using statistic shape model
Xiu-Yun SU ; Jie HE ; Wei ZHAO ; De-Shun SUN ; Heng LI ; Yi-Yi OU ; Guo-Xian PEI
Acta Anatomica Sinica 2024;55(6):715-720
Objective To construct a three-dimensional statistical shape model of the pelvis and analyze the individual variation and gender differences of the three-dimensional shape of the pelvis.Methods We collected CT data from 201 Chinese individuals and used deep learning to automatically reconstruct three-dimensional models of the pelvis.Through three-dimensional model registration,dense correspondence mesh mapping,and the use of statistical shape modelling(SSM)and principal component(PC)analysis method,we extracted models of variations(MoV)of pelvic shape changes and statistically compared the shape MoV between males and females.Results We analysed the top 10 principal components of shape variations,which accounted for 86.1%of the total variability.Among them,PC01,PC02,and PC04 showed significant differences between genders(P<0.001),accounting for a total variability of 60.1%.PC08 and PC 10 demonstrated pelvic asymmetry,accounting for a total variability of 3.8%.Conclusion We constructed a three-dimensional statistical shape model of the pelvis in Chinese individuals,revealing the morphological variation and sex differences of Chinese pelvis.
10.Lung-protective effect of esketamine combined with distal limb ischemic preconditioning in elderly patients undergoing thoracoscopic radical surgery for lung cancer:a randomized controlled trial in 160 cases
Yang YANG ; Gang LIU ; Yi OU ; Wenqi LU
Journal of Southern Medical University 2024;44(3):484-490
Objective To evaluate the effect of esketamine combined with distal limb ischemic preconditioning(LIP)for lung protection in elderly patients undergoing thoracoscopic radical surgery for lung cancer.Methods This randomized trial was conducted in 160 patients undergoing elective thoracoscopic surgery for lung cancer,who were randomized into control group(with saline injection and sham LIP),esketamine group,LIP group,and esketamine+LIP group(n=40).Before anesthesia induction,according to the grouping,the patients received an intravenous injection with 0.5 mg/kg esketamine or 10 ml saline(in control group).LIP was induced by applying a tourniquet 1-2 cm above the popliteal fossa in the left lower limb to block the blood flow for 5 min for 3 times at the interval of 5 min,and sham LIP was performed by applying the tourniquet without pressurization for 30 min.Oxygenation index(OI)and alveolar-arterial PO2 difference(A-aDO2)were calculated before induction(T0),at 30 min(T0.5)and 1 h(T1)of one-lung ventilation(OLV),and at 1 h after two-lung ventilation(T3).Serum levels of SP-D,CC-16 and TNF-α were measured by ELISA at T0,T1,T2(2 h of OLV),T3,and 24 h after the operation(T4).The length of hospital stay and postoperative pulmonary complications of the patients were recorded.Results Compared with those in the control group,the patients in the other 3 groups had significantly lower CC-16,SP-D and TNF-α levels,shorter hospital stay,and lower incidences of lung infection and lung atelectasis(all P<0.05).Serum CC-16,SP-D and TNF-α levels,hospital stay,incidences of complications were significantly lower or shorter in the combined treatment group than in esketamine group and LIP group(all P<0.05).Conclusion In elderly patients undergoing thoracoscopic radical surgery for lung cancer,treatment with esketamine combined with LIP can alleviate acute lung injury by enhancing anti-inflammatory response to shorten postoperative hospital stay,reduce lung complications and promote the patients'recovery.

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