To overcome cisplatin resistance in lung cancer cells,a novel metal-organic framework (MOF) nanocarrier delivery system with chemo-photodynamic combined efficacy was developed.
Methods
MOFs were synthesized using the Tetrakis(4-hydroxyphenyl) porphyrin (THPP) and loaded with cisplatin through ultrasonic emulsification method to form a drug-loaded nanosystem (Cisplatin@MOFs),which were activated under the near-infrared irradiation.The physicochemical properties were characterized though the particle size,Zeta potential,and the singlet oxygen detection experiments.The particle size and surface zeta potential were measured by the dynamic light scattering (DLS) and the shape of samples was visualized by transmission electron microscopy (TEM).The singlet oxygen release was detected by the ROS indicator.The cisplatin release from Cisplatin@ MOF nanoparticles were assessed by the dialysis diffusion method.In vitro cytotoxicity was observed by using a CCK8 (cell counting kit-8) assay.The combined anti-tumor effect was investigated through the measurement of cell proliferation and cell migration.The proliferation was observed by Ki67 fluorescence staining and the cell migaration was assessed by the wound-healing experiment.Western Blot analysis was employed to explore the underlying regulatory mechanisms.
Results
Transmission electron microscopy (TEM) characterization showed that the Cisplatin@MOF exhibited a polygonal spherical structure with a particle size of(431.33±21.47)nm.The dynamic light scattering (DLS) measurements indicated an average size of approximately 458 nm for Cisplatin@ MOF,with a polydispersity index (PDI) of 0.482.The Zeta potential values were(3.20±0.23)mV for MOF and(6.63±0.81) mV for Cisplatin@ MOF,respectively.Under near-infrared irradiation,the MOF nanoparticles could release the singlet oxygen.The ROS generation ability of the MOFs was detected by the indicater (DPBF) and the results demonstrated the photodynamic protential.The loading capacity of cisplatin in the Cisplatin@ MOF nanodrug delivery system was (41.73±2.66)%.Release tests showed that Cisplatin@MOF could release cisplatin under acidic conditions by a dialysis method.Then we used the confocal laser scanning microscopy (CLSM) to examine the cellular internalization of MOF nanoparticles.In vitro we conducted a cell viability assay (CCK8) to evaluate MOF's cytotoxicity in cisplatin-resistant lung cancer cells (A549-DDP).The results showed that compared to control and no-laser groups,a significant reduce in cell viability was observed in cells treated under light irradiation.Cisplatin@MOF under light irradiation exhibited the strongest damage on the cisplatin-resistant lung cancer cells.We used fluorescence immunostaining analysis of Ki67 marker to assess the cell proliferation.The results revealed that the lower Ki67 expression in the cells treated under light irradiation compared to the control and dark groups.Cisplatin@MOF under light irradiation showed the lowest Ki67 expression of cell proliferation.It was conducted that the cell scratch test to examine the impact of MOFs on cell migration.The results revealted that the cells receiving the later treatment demonstrated weak cell migration compared to the control and dark groups.Cisplatin@MOF under light irradiation exhibited the weakest cell migration compared to other rtreatmens.Thse results confrm a significant chemophotothermal combined antitumor effect on cisplatin-resistance tumor cells.Futhernore,we used the Western Blot assays to ascess the protein levels of Bcl-2/Bax signaling pathway.Cells treated with light irradiation inhibited significantly lower levels of Bcl-2 expresion compared to control and nolaser groups.And the protein levels of Bax were significantly increased in the cells from the laser groups compared to the control and dark groups.These results suggested Bcl-2/Bax signaling pathway's potential as the ksy mechanism for combined antitumor effects.
Conclusion
In summary,we developed a multifunctional MOFs-based drug delivery system that combines chemotherapy and PDT for a novel strategy.This system effectively overcomes cisplatin resistance and demonstrates combined therapeutic efficacy through chemophotodynamic therapy.These findings suggest it could potentially serve as a more efficient targeted therapy for lung cancer.
To analyze the disease burden of chronic obstructive pulmonary disease(COPD) in China from 1990 to 2021,and the trend of change from 2022 to 2050,in order to provide a reference for the prevention and control of COPD.
Methods
Chinese disease burden and risk factors of COPD from 1990 to 2021 were extracted in the Global Burden of Disease 2021.Percentage change and estimated annual percentage change were applied to analyze the evolution of the disease burden.And which in different sex and age groups was also analyzed.Deaths due to all risk factors were attributed and Bayesian age-periodcohort modeling was used to predict trends of COPD from 2022 to 2050.
Results
The number of incident,death,disability-adjusted life years(DALYs) in 2021 were 4 434 437.77,1 285 433.17 and 23 640 320.96,which was 105.20%,3.84%,and -9.42% higher than 1990,reapectively.The age-standardized rate of incident,death and DALYs showed a downward trend from 1990 to 2021,estimated annual percentage change was -0.84%,-4.25% and -4.19%,reapectively.In 2021,the number of incident,death,disability-adjusted life years(DALYs) were 2 226 848.07,752 026.94 and 13 480 743.00 among males,which was 112.81%,17.28% and -2.98% higher than 1990,reapectively.For females,there were 2 207 589.70 cases of incidence and 533 406.24 deaths,with 10 159 577.96 DALYs,representing 98.06%,-10.61% and -16.75% higher than 1990,reapectively.Indicating a gender difference.Disease burden increased significantly with age,with the peak of incidence and DALYs for males were in the 65-69 and 70-74 years old,and for females in the 70-74 and 80-84 years old.The peak in deaths for both genders was in the 80-84 age group,with no gender difference.The risk factors leading to COPD-related deaths have changed over time,with smoking being the leading risk factor in recent five years,and the most common risk factors for males and females being smoking and particulate matter pollution,respectively.The age-standardized rate of incidence,death and DALYs will continued decrease from 2022 to 2050.,with expected decreases to 139.71/100 000、15.80/100 000 and 362.03/100 000 by 2050,respectively.
Conclusion
The disease burden of COPD in China remains severe,and effective prevention and treatment strategies should beformulated for high-risk populations and risk factors.
To analyze the anti-fibrotic efficacy of Nintedanib and Pirfenidone in idiopathic pulmonary fibrosis (IPF) and non-idiopathic pulmonary fibrosis (Non-IPF).To clarify the impact of the two drugs on the important prognostic indicators of forced vital capacity (FVC) decrease and all-cause mortality.
Method
A comprehensive search was conducted in PubMed,Embase,and MEDLINE databases updated to March 2024.It was included the randomized controlled trials which evaluated the degree of FVC reduction and mortality in IPF and Non-IPF patients treated with nintedanib or pirfenidone.SPSS 25.0 software was used for data standardization when the data format of the outcomes was inconsistent.Review Manager 5.4 software was used for statistical analysis.The random effects model was used to assess standardized mean difference (SMD)and confidence intervals (CI). I2 was used to assess the heterogeneity.Egger's test and funnel plot were used to evaluate publication bias.Egger's test showed (P<0.05) or the funnel plot showed asymmetry,indicating the presence of publication bias.Sensitivity analysis was conducted by conducting individual deletion studies and comparing the changes in the average effect size before and after deletion to determine the robustness of the summary results.
Result
A total of 17 articles with 5099 patients were included in this study,2 684 cases in obseruation greup,2 415 cases in control group.The Meta-analysis showed that when the treatment of various types of pulmonary fibrosis with Pirfenidone or Nintedanib,the grade of FVC decrease in the observation group was significantly smaller than that in the control group (SMD:1.48,95%CI:0.82-2.15).The all-cause mortality rate was also significantly decreased in the observation group than in the control group (OR:0.59,95%CI:0.45-0.77).There was no heterogeneity among the studies, I2=0%, P=0.62,and sensitivity analysis showed stable results.The Subgroup analysis results showed that Nintedanib treatment for IPF (SMD:3.39,95%CI:2.77-4.01) and Non-IPF (SMD:2.25,95%CI:0.91-3.59) both attenuated the FVC decrease,and sensitivity analysis showed stable results.Pirfenidone treatment for IPF (SMD:0.37,95%CI:0.06-0.67) and Non-IPF (SMD:1.13,95%CI:0.14-2.12) can also inhibited FVC decrease,but sensitivity analysis found that there were some small sample size studies,indicating unstable results.Nintedanib had a prior effect on the all-cause mortality when treated for IPF (OR:0.60,95%CI:0.38-0.94),while had no significant effect on Non-IPF (OR:0.81,95%CI:0.43-1.54).Pirfenidone had a prior effect on the all-cause mortality when treated for IPF (OR:0.55,95%CI:0.37-0.82),while had no significant effect on Non-IPF (OR:0.40,95%CI:0.13-1.23).
Conclusion
In the summary analysis of a large sample,the overall therapeutic effect of the two drugs is effective.Nintedanib and Pirfenidone can attenuate the FVC decrease in various types of pulmonary fibrosis patients and reduce the mortality.The therapeutic effect of nintedanib is stable.the effect of pirfenidone on Non-IPF is not so stable because of lack of big sample trials support and further research is needed to clarify the conclusion.
To investigate the relationship between serum sphingosine 1-phosphate (S1P)level,disease severity and immunosuppressive therapy in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD).
Methods
All of 85 cases of CTD-ILD patients admitted to the Department of Respiratory and Critical Care Medicine,Affiliated Hospital of Jining Medical College from December 2022 to January 2024 were selected as the study objects.The severity of CTD-ILD disease and the extent of lung involvement were assessed using carbon monoxide dispersion as a percentage of expected value(DLCO%) and high-resolution CT ( HRCT) scanning.All CTD-ILD patients received standard cyclophosphamide (CTX) impulse therapy and were divided into response subgroup and response subgroup according to treatment effect.Serum S1P levels in CTD-ILD patients were detected by enzyme-linked immunosorbent assay at baseline,3 months after treatment and 6 months after treatment.Spearman method was used to evaluate the relationship between serum S1P and other indicators.
Results
In the 85 cases,34 cases(40.00%) were mild CTD-ILD,38 cases (44.71%) were moderate CTD-ILD,and 13 cases (15.29%) were severe CTD-ILD.Compared with mild patients,lung function (FVC%,FEV1%,DLCO%) was significantly decreased in moderate and severe patients (F=20.206, F=33.587, F=71.133, P<0.05).The baseline serum S1P levels of CTD-ILD patients in mild,moderate and severe groups were 663.70 (249.76,1 045.27) ng/ml,877.47 (705.31,1 861.98) ng/ml and 1 624.38 (1 016.52,3 753.87) ng/ml(H=14.028, P<0.001).Spearman and multivariate linear regression analysis showed that baseline serum S1P level in CTD-ILD patients was correlated with FVC% (β=-0.009, t=-3.943, P<0.001),FEV1% (β=-0.009, t=-3.912, P<0.001),DLCO% (nonstandardized coefficient β = -0.008, t = -3.871, P <0.001) was still negatively correlated.After CTX shock therapy,all 85 CDT-ILD patients received HRCT scans and PFT at three time points,64 patients were diagnosed as effective or stable (response subgroup),and the remaining 21 patients(24.71%) were classified as ineffective subgroup.The baseline PLT/LYM ratio[129.06(88.64,184.32)vs.193.62(120.24,265.94)] and CRP level[4.99(3.30,20.07)mg/L vs. 11.90(3.69,31.07)mg/L] in the remission subgroup were slightly lower than those in the ineffective subgroup (P<0.05).Further trend analysis showed that the serum S1P level in the remission subgroup gradually decreased over time,and at 3 and 6 months after treatment,the serum S1P level[851.13(412.68,1 497.11)ng/ml vs. 962.07(438.99,1 561.03)ng/ml] in the remission subgroup was lower than that in the ineffective subgroup (P<0.05).
Conclusion
Serum S1P levels tend to decrease in patients who are in remission after CTX shock therapy,S1P may also be a supportive indicator of treatment effectiveness in CTD-ILD patients.
To analyze the correlation of lung ultrasound with the severity of connective tissue disease-associated interstitial lung disease (CTD-ILD).
Methods
All of 47 patients with connective tissue disease admitted to our hospital from November 2023 to January 2024 were selected.According to the results of high resolution CT (HRCT),24 cases of CTD-ILD were treated as observation group and the other 23 cases of CTD-non ILD were treated as control group.Lung function examination was performed in observation group.The results of pulmonary ultrasound examination,clinical and pulmonary function data,HRCT interstitial lesion score were statistically analyzed.
Results
The ultrasonographic B-line scores of 14 intercostal 25 (12,80),50 intercostal 79(37,265) and posterior basal intercostal 20 (0,30) in the observation group were higher than those of the control group 14 intercostal 0(0,0),50 intercostal 4(0,9) and posterior basal intercostal 0(0,3) (P<0.001).The area under the curve was 0.926 (95%CI:0.852-0.999, P<0.001) of intercostal lung ultrasound 50 and 0.951 (95%CI:0.890-1.000, P<0.001) of intercostal lung ultrasound 14.The area under the posterior basal intercostal curve was 0.813 (95%CI:0.683-0.942, P <0.001).B-line sensitivity of 50 intercostal,14 intercostal and posterior basal intercostal lung ultrasound was 83.3%,87.5%and 75.0%,respectively.The B-line specificity of 50 intercostal lung ultrasound,14 intercostal lung ultrasound and posterior basal intercostal lung ultrasound were 78.3%,87.0% and 73.9%,respectively.The cut-off values of B-line ultrasound score of 50 intercostal,14 intercostal and posterior basal intercostal lung were >10,3 and 2,respectively.The positive predictive values of 50 intercostal,14 intercostal and posterior basal lung ultrasound B-line scores were 87.5%,83.3% and 76.2%,and the negative predictive values were 78.3%,88.0% and 69.2%,respectively.Ultrasonographic B-line scores of 50 intercostal,14 intercostal and posterior basal intercostal lung were positively correlated with HRCT semi-quantitative scores (P<0.001),and negatively correlated with FVC/pre and DLCO/pre,respectively (P<0.001).The incidence of interruption of pleural line continuity was higher in observation group 17 cases(73.91%) than control group 4 cases(16.67%)(P<0.001).
Conclusion
Lung ultrasonography can determine the severity of CTD-ILD.14 intercostal lung ultrasound was better than 50 intercostal and posterior basal intercostal lung ultrasound in predicting CTD-ILD.
To analyze the relationship between circulating miR-486-5p,miR-148a-3,miR-744-5p and obstructive sleep apnea (OSA) risk stratification and immune monitoring.
Methods
All of 45 OSA patients admitted to our hospital from May 2021 to May 2022 were selected and divided into mild OSA group (11 cases),moderate OSA group (11 cases) and severe OSA group (23 cases) according to apnea and hypopnea index (AHI).Whole blood T cells were detected by flow cytometry,plasma miR-486-5p,miR-148a-3 and miR-744-5p were analyzed by reverse transcription-quantitative polymerase chain reaction.The relationship between circulating miR-486-5p,miR-148a-3 ,miR-744-5p and OSA risk stratification was analyzed.
Results
Microarousal index 13.60 (3.20,32.65),SpO2 <90%,total duration 27.00 (17.25,46.25) min in severe OSA group were higher than those in mild OSA group 0.00 (0.00,0.25),14.60 (8.00),21.60) min moderate OSA group 0.30 (0.05,1.15),10.20 (9.85,16.80) min,The average SpO2(91.10±4.07)% and CD4+/CD8+ T lymphocyte ratio (1.11±0.26) in severe OSA group were lower than those in mild OSA group (95.82±1.25) % and (1.51±0.56).Moderate OSA group (94.73±1.35)%,(1.43±0.54) (P<0.05).The plasma miR-486-5p (0.85±0.41) and miR-148a-3 (0.53±0.28) in severe OSA group were lower than those in mild OSA group (1.35±0.56),miR-148a-3 (1.03±0.32) and moderate OSA group (1.31±0.40),miR-148a-3 (1.06±0.17) (P<0.05); The plasma miR-744-5p (2.39±1.01) in severe OSA group was higher than that in mild OSA group (1.51±0.83) and moderate OSA group (1.59±0.81) (P<0.05).Pearson correlation analysis showed that the expression of miR-486-5p (r=0.354, P=0.017) and miR-148a-3 (r=0.232, P = 0.029) in plasma was positively correlated with the ratio of CD4+/CD8+ T lymphocytes.The combined expression of miR-486-5p,miR-148a-3,and miR-744-5p in plasma was superior to the identification of severe OSA alone,and the area under the receiver operating characteristic (ROC) was 0.978 (95%CI:0.883-0.999),the sensitivity and specificity were 86.96% and 95.45%,respectively.
Conclusion
Plasma miR-486-5p,miR-148a-3p and miR-744-5p are correlated with the severity of OSA disease,and can assist in the risk stratification of OSA disease.
To explore and verify the key Ferroptosis related genes and drug sensitivity analysis that affect the prognosis of lung adenocarcinoma (LUAD).
Methods
Firstly,data were downloaded from TCGA and GEO databases.Secondly,the transcriptome expression profiles downloaded from the databases were subjected to differential expression analysis,GO and KEGG enrichment analysis,WGCNA co-expression analysis,intersection with iron death related genes were taken and KM survival analysis was performed to obtain key genes,and drug sensitivity analysis was performed.
Results
964 (259 upregulated and were downregulated)and 193 differentially expressed genes(108 upregulated and 85 downregulated) were obtained from TCGA dataset and GEO dataset respectively,which were related to extracellular matrix organization and cell adhesion molecule.5 303,362 genes were obtained by WGCNA co-expression analysis,which were intersected with Ferroptosis related genes,and two characteristic genes CP and CA9 were obtained.Compared with normal samples,CP and CA9 were highly expressed in LUAD samples (P<0.001),which were mostly highly expressed in pancarcinoma.KM survival analysis showed that those with high expression of CA9 had a short survival period (P<0.05),while there was no statistically significant difference between CP analysis and LUAD survival period (P>0.05).CA9 was a risk gene of LUAD and positively correlated with the sensitivity of the two drugs.
Conclusions
The key Ferroptosis related gene CA9 which affects the prognosis of lung adenocarcinoma was explored and verified by bioinformatics,which provides a potential therapeutic target for lung adenocarcinoma.
To investigate clinical implications of dynamic determination of plasma long non-coding RNA SOX2-OT in patients with pulmonary hypertension (PH) associated with chronic obstructive pulmonary disease (COPD).
Methods
It was selected that 120 patients with acute exacerbation of COPD(AECOPD) as the study subjects in our hospital from October 2020 to January 2023.According to the level of pulmonary artery systolic pressure (PASP),the patients were divided into AECOPD group(control group, n=78) and AECOPD-associated PH group (observation group, n=42).Plasma long non-coding RNA SOX2-OT,interleukin (IL)-6,IL-8,and N-terminal pro brain natriuretic peptide (NT-ProBNP),PASP,arterial blood gas,lung function,and 6-minute walking distance (6MWD) in the two groups were dynamically determined at admission,as well as 10 days,3 months,6 months,and 12 months after admission.Number of times of AECOPD and rates of mortality in the two groups were recorded during the 12 months of follow-up period.
Results
There were statistical differences with respect to 11 variables including the plasma long non-coding RNA SOX2-OT,IL-6,IL-8,and NT-ProBNP,PASP,pH value,PaO2,PaCO2,the percentage of forced expiratory volume in one second (FEV1%),the diffusing capacity for carbon monoxide (DLCO),and 6MWD,between two groups,at admission and 10 days after admission,respectively (all P <0.05).Except for the plasma long non-coding RNA SOX2-OT and PASP,the rest 9 variables 10 days after admission were statistically different from those at admission in the control group (all P<0.05),whereas all the 11 variables above 10 days after admission were statistically different from those at admission in the observation group (all P<0.05).The pairwise comparison among patients at 3-month,6-month,and 12-month demonstrated no statistical significance for all the 11 parameters above in the control group (all P>0.05).There were statistical differences in the PASP and plasma levels of long non-coding RNA SOX2-OT and NT-ProBNP (all P<0.05),while there were no statistical difference in the plasma levels of IL-6 and IL-8(both P>0.05),when comparing patients at 12-month with those at 3-month and 6-month,respectively,in observation group.There were statistical differences with regard to the pH value,PaO2,PaCO2,FEV1%,DLCO,and 6 MWD,in the pairwise comparisons among patients at 3-month,6-month,and 12-month in the observation group (all P<0.05).The mean number of times of AECOPD and mortality rate in the observation group were statistically greater than those in the control group ,respectively,during the 12 months of followup period (both P<0.05).
Conclusion
Plasma level of long non-coding RNA SOX2-OT in AECOPD patients with AECOPD-associated PH is significantly higher than that in those without.Dynamic determination of plasma level of long non-coding RNA SOX2-OT has certain clinical implications in the prediction of AECOPD and prognosis of patients with COPD-associated PH.
To explore the efficacy and mechanism of OX40 antibody agonist (ES102) in humanized OX40 mouse NSCLC model.
Methods
Mouse Lewis lung cancer cells were detected using flow cytometry (Lewis lung cancer cells,CD44 expression in LLC); OX40 humanized mouse NSCLC tumor-bearing model (vehicle control group,ES102 treatment group at different doses) and colon cancer tumor-bearing model(positive vehicle control group and positive control group) were constructed respectively,To evaluate the tumor suppressive level of ES102 in different groups; Serum interferon- γ was measured by ELISA (interferon- γ,IFN- γ) and interleukin-17 (interleukin-17,IL-17) secretory level; Expression of PI3K,NFAT,CD44,NapsinA and SYN by western blot (Western blot); The expression of the immune-infiltrating cells was determined by RNA transcriptome sequencing.
Results
The CD44 positive rate in LLC cells showed 99.58%and low expression of NapsinA protein,suggesting that LLC murine-derived lung cancer cell lines had NSCLC properties.In the humanized OX40 mouse NSCLC model,ES102 inhibited NSCLC,but on Day 11,Day 14,Day 18,and Day 21 in the positive vehicle control (P=0.0004, t=5.712; P<0.0001, t=9.368; P<0.0001,t=10.364; P<0.0001, t=13.37).The content of plasma IL-17 in humanized mice was significantly differently expressed between different samples (F=7.703, P=0.0004); The secretion content of IL-17 in the positive control group (58.24±18.11)pg/ml than the ES102 (2 mg/ml) group (21.87±11.74)pg/ml,The ES102(5 mg/ml) group (18.49±10.17)pg/ml and the ES102 (10 mg/ml) group (20.47±10.52)pg/ml(P<0.05);Higher IFN- γ in NSCLC ES102 (10 mg/ml) than the control,ES102 (2 mg/ml) and ES102 (5 mg/ml)(P<0.05).PI3K expression was not seen in the positive control group and was highly expressed in the untreated group and the ES102 experimental group (2 μg/kg to 10 μg/kg)(P<0.05).As a nuclear factor in activated T cells,NFAT was expressed in a trend consistent with PI3K,without a statistically significant difference between the groups(P>0.05).After transcriptome sequencing of NSCLC and positive control mice,further transcriptome sequencing and deconvolution analysis showed that the proportion of Tregs cells infiltrated was (1.95±0.02)%,which was lower than that of Tregs cells infiltrated in the positive control group (7.2±0.03)%(P<0.05).
Conclusion
The efficacy of ES102 in humanized NSCLC mice is lower than colon cancer,and the difference may be related to the decreased secretion of IL-17 and the infiltration of Tregs cells in the microenvironment.
To analyze the lobar emphysema ratio (LER) for predicting stage Ⅰ-ⅢA nonsmall cell lung cancer (non-small cell lung cancer).The clinical significance of video-assisted thoracoscopic/thoracic surgery (VATS) after pulmonary resection for persistent air leak (PAL).
Methods
All of 117 patients with NSCLC treated by VATS pulmonary lobectomy from January 2021 to January 2024 were selected as subjects.PAL (lung leakage time >5 days after pneumonectomy) was recorded,19 cases of PAL were observed and 98 cases without PAL were control group.Spearman rank correlation was used to analyze the correlation.Multivariate Logistic regression analysis of PAL risk factors after VATS in NSCLC patients.Subject operating characteristic curves were used to predict PAL risk after VATS in NSCLC patients.
Results
67 cases had gas leakage on the first day after operation,48 cases stopped gas leakage within 5 days,19 cases (16.23%) had gas leakage >5 days.There was no death during hospitalization,and no chest tube drainage was performed after discharge.The average length of hospitalization was (6.62±4.01) d and the duration of air leakage was (2.93±3.42) d.The emphysema ratio (ER) of 0.11 (0.02,1.01)% in the observation group was higher than that of the control group by 2.13 (0.85,3.07)%.The upper lobe of the right lung in the observation group was 0.10(0.01,1.38) and the middle lobe of the right lung was 0.18(0.02,1.00)%,lower lobe of right lung 0.04(0.00,0.46)%,upper lobe of left lung 0.09(0.01,1.32)%,lower lobe of left lung 0.06(0.00,0.53)% were higher than those of control group 2.59(0.39,6.16)%,middle lobe of right lung 0.72(0.36,2.00)%,right inferior lobe 1.29(0.13,2.36)%,left superior lobe 1.52(0.74,2.75)%,left inferior lobe 1.75(0.35,3.05)%.Spearman rank correlation analysis showed a strong positive correlation between ER and LER (rho=0.857, P=0.000).LER predicted that the AUC of PAL after VATS in NSCLC patients was 0.876 (95%CI:0.817-0.922),the optimal cut-off value (0.75),sensitivity and specificity were 85.71% and 80.28%,and positive and negative predictive values were 82.27% and 84.03%,respectively.The AUC of ER predicting PAL after VATS in NSCLC patients was 0.792 (95%CI:0.723-0.850),the optimal cut-off value (0.18) was 92.86%,the specificity was 57.75%,and the PPV and NPV were 70.12% and 88.34%,respectively.LER predicted that PAL occurrence was higher than ER (Z=2.875, P=0.004).Logistic regression analysis showed that smoking history (OR=5.888, P=0.037),T2-T3 tumor stage (OR=2.696, P=0.036),respiratory complications (OR=2.928, P=0.030) and LER >0.75 (OR=15.693, P=0.000) predicted PAL.
Conclusion
ER and LER can predict PAL in patients with stage Ⅰ-ⅢA NSCLC after pulmonary resection of VATS,and the prediction of LER is significant.
To analyze value of hematological features after intensive treatment of pulmonary tuberculosis (PTB).
Methods
All of 162 newly diagnosed PTB patients admitted to our hospital from May 2020 to June 2022 were selected as subjects.After 2 months of intensive treatment,112 patients with negative sputum were included in the control group by smear microscopy and sputum culture,and 50 cases without negative sputum were included in the observation group.Peripheral venous blood was collected before and after anti-tuberculosis treatment,and 24 kinds of hematological parameters were detected.
Results
After treatment,neutrophils count [NEU,4.92 (3.73,6.57) ×109/L vs. 6.02(4.76,7.52) ×109/L] and monocytes count[MONO,0.50 (0.32,0.72) ×109/L vs. 0.89(0.47,1.08) ×109/L],monocyte to lymphocyte ratio [MLR,0.23 (0.16,0.34) vs. 0.43 (0.25,0.59)],platelet to lymphocyte ratio [PLR,142.10 (82.60,184.00) vs. 155.50 (102.60,193.90)],neutrophil to lymphocyte ratio [NLR,2.29 (1.57,3.05) vs.2.88(2.23,4.17)],systemic immunoinflammatory index [SII,568.60 (361.90,1 018.60) vs. 735.40 (575.20,1 110.50)],platelet count [PLT,296.00 (201.00,390.00)×109/L vs. 259.00 (225.00,280.00)×109/L],platelet [PCT,0.15 (0.13,0.19) vs. 0.18 (0.14,0.25)],erythrocyte sedimentation rate [ESR,45.00(25.00,85.00)mm/1 h vs. 75.00 (56.00,95.00)mm/1 h] and C-reactive protein [CRP,9.30 (9.10,11.30) mg/L vs. 9.70 (9.10,11.60)mg/L] were significantly higher than those in group.Hematocrit [HCT,42.30 (39.10,45.90) % vs. 38.20 (35.20,40.40)%] was significantly lower than that in sputum conversion to Yin group (P<0.05).Compared with before treatment,white blood cell count (WBC),NEU,MONO,MLR,NLR,PLR,SII,PLT,MPV,PCT,ESR and CRP were significantly decreased,while red blood cell count (RBC),hemoglobin (Hb) and HCT were significantly increased in the control group after treatment (P<0.05).In the observation group,NEU,NLR,MPV,ESR and CRP were significantly decreased after treatment,while RBC,HCT and RDW-SD were significantly increased (P<0.05).ROC curve was used to evaluate the predictive value of a single indicator for sputum not turning negative after treatment,and the results showed that the area under the prediction curve (AUC) of a single hematology parameter was<0.75.Logistic regression was used to construct the combined model,and the AUC of each model was significantly higher than that of a single hematology parameter (P<0.05).Model 6 (NEU,MLR,NLR,PLR,SII,HCT,PCT,ESR,CRP) had good accuracy and predicted an AUC of 0.852 (95%CI:0.787 ~0.917).
Conclusion
The combined model of hematology parameters can be used as a noninvasive prognostic tool for the outcome of PTB intensive treatment.
To analyze the influencing factors of pulmonary reexpansion after chronic tuberculous empyema operation.
Methods
A total of 73 patients with chronic tuberculous empyema treated in our hospital from January 2019 to September 2023 were selected as the subjects,followed up for 6 months,56 cases with complete pulmonary reexpansion were the control group,and 17 cases with partial pulmonary reexpansion and no pulmonary reexpansion were the observation group.By comparing the two groups of general data,Logisic regression model was used to analyze the influencing factors of pulmonary reexpansion in chronic tuberculous empyema.ROC curve was used to predict pulmonary reexpansion of chronic tuberculous empyema.
Results
The body mass index (BMI) of the observation group (18.54±1.50)kg/m2 was lower than that of the control group (20.08±1.97) kg/m2.In the observation group,8 patients (47.06%) had a history of smoking and acid-fast bacilli.Sputum culture positive 9 cases (52.94%),AFB pleural effusion culture positive 4 cases(23.53%),operation time (4.16±0.49)h,C-reactive protein (40.21±2.24)g/L were higher than the control group in 7 cases (12.50%),AFB sputum culture positive 7 cases(12.50%),AFB Pleural effusion culture was positive in 3 cases (5.36%),operative time (3.66±0.44)h,C-reactive protein (38.10±1.98)g/L (P<0.05);Multivariate Logistic regression analysis showed BMI (OR:0.063,95%CI:0.006-0.641),smoking history(OR:5.320,95%CI:1.148-24.645),AFB sputum culture (OR:10.856,95%CI:1.593-73.987),AFB pleural effusion culture (OR:2.568,95%CI:1.031-6.397),C-reactive protein (OR:4.704,95%CI:1.274-17.359),operation time (OR:9.895,95%CI:1.457-67.191) was the influential factor of poor pulmonary reexpansion after chronic tuberculous empyema operation (P<0.05).ROC curve showed that BMI,smoking history,positive proportion of AFB sputum culture,AFB pleural effusion culture,operation time and C-reactive protein in the diagnosis of chronic tuberculous chest abscess postoperative poor lung reexpansion area under curve,AUC was 0.739,0.673,0.702,0.591,0.765,0.789.
Conclusion
BMI,smoking history,positive proportion of AFB sputum culture,AFB pleural effusion culture,operation time and C-reactive protein are the influential factors of lung reexpansion after chronic tuberculous empyema operation.
To investigate the effect of the length and source of malignancy history on the diagnostic efficacy of Lung-RADS (lung imaging-reporting and data system) 2022 and PNI-GARS (pulmonary node imaging-grading and reporting system) in pulmonary nodules (PNs).
Methods
Chest computed tomography and clinical data of PNs in 451 patients with a history of cancer who underwent surgical resection in The First Affiliated Hospital of Chongqing Medical University from January,2018,to November,2021,were retrospectively collected and evaluated based on Lung-RADS and PNI-GARS,respectively.All PNs were divided into 2 groups:the prior lung cancer (PLC)144 cases and the prior extrapulmonary cancer (PEPC)groups 307cases.The diagnostic agreement rate(AR)of Lung-RADS and PNI-GARS was evaluated based on the pathological diagnosis of nodules after operation.The AR of the two systems and the composition ratios of PNs with different types between different groups were calculated and compared.
Results
A total of 451 patients with 565 PNs were included in this study.These patients were divided into the PLC group (<5 years:135 cases,175 PNs; ≥5 years:9 cases,12 PNs) and the PEPC group (<5 years:219 cases,278 PNs; ≥5 years:88 cases,100 PNs).The diagnostic AR of Lung-RADS of partial solid nodules (93.0%) and solid nodules (88.1%) was close (P = 0.131),while both were higher than that of the ground-glass nodules(24.0%,all P values <0.001).However,the diagnostic AR of PNI-GARS of partial solid nodules was the highest (100%,all P<0.001),and the AR of solid nodules and ground glass nodules were similar with each other (88.5% vs. 84.8%, P=0.273).Within 5 years,the composition ratio of PNs and the diagnostic AR of Lung-RADS (PLC:58.9%,PEPC:76.6%) between the PLC and PEPC groups were all different (all P values<0.001),and the others (composition ratio of PNs & the diagnostic AR:PLC (≥5 years) vs. PEPC(≥5 years); PLC (<5 years) vs. PLC (≥5 years); PEPC (<5 years) vs. PEPC (≥5 years) were similar(all P values >0.05).On the contrary,the diagnostic AR for PNI-GARS did not vary regardless of the length of previous cancer history or the type of previous malignancy.
Conclusion
The diagnostic efficiency of PNI-GARS would not be affected by the length of previous cancer history and the origin of previous malignancy,and the length of prior cancer history may impact the diagnostic performance of Lung-RADS.
To analyze the effects of different CT reconstruction algorithms on the effectiveness of artificial intelligence (AI)-assisted pulmonary nodules identification.
Methods
A total of 200 patients who underwent lung high resolution CT examination in our hospital from December 2022 to April 2023 were selected and reconstructed with a thin layer thickness of 0.625 mm using lung high-resolution algorithm(Lung) and standard algorithm (Stnd).The raw data obtained by the two reconstruction algorithms were transmitted to the AI-assisted diagnostic software for automatic detection of pulmonary nodules,and the density and size of the nodules were recorded respectively.According to the size of the nodules,the solid nodules were divided into <5 mm and ≥5 mm.The subsolid nodules were divided into <8 mm and ≥8 mm.The true positive and false positive numbers of nodule identification by AI in each group under the two reconstruction algorithms are separately recorded,and the sensitivity of AI for the identification of pulmonary nodules was calculated.To compare whether there is a difference in the efficiency of AI software in identifying pulmonary nodules under the two reconstruction algorithms.
Results
There were 996 solid nodules <5 mm,the true positive numbers and sensitivity were 697(69.98%) under Lung algorithm and 817(82.03%) under Stnd algorithm.There were 74 nodules ≥5 mm,the true positive numbers and sensitivity were 47(63.51%) under Lung algorithm and 67(90.54%) under Stnd algorithm.There were 358 subsolid nodules <8 mm,the true positive numbers and sensitivity were 230(64.25%) under Lung algorithm and 340(94.97%) under Stnd algorithm.There were 35 nodules ≥8 mm,the true positive numbers and sensitivity were 35(100.00%) under Lung algorithm and 34(97.14%) under Stnd algorithm.The sensitivity of AI to identify 2 groups of solid nodules of different sizes(<5 mm and ≥5 mm) under Stnd algorithm was higher than that of Lung algorithm.The sensitivity of the Stnd algorithm was higher than that of the Lung algorithm for the identification of subsolid nodules <8 mm (P<0.05),and there was no difference between the two algorithms for the identification of nodules ≥8 mm(P>0.05).
Conclusion
There are differences in the identification efficiency of AI-assisted pulmonary nodules under different CT reconstruction algorithms.The sensitivity of Stnd reconstruction algorithm is better than Lung algorithm for the recognition of solid pulmonary nodules.For the identification of subsolid pulmonary nodules,the sensitivity of Stnd algorithm for nodules <8 mm is higher than that of Lung algorithm,but the false positives are higher.There is no difference between the two algorithms for nodules ≥8 mm and both have higher sensitivity.
To analyze prognostic significance of scavenger receptor class A member 5(SCARA5) methylation in adjuvant chemotherapy (ACT) for non-small cell lung cancer (NSCLC).
Methods
All of 69 patients with stage ⅠA~ⅢA NSCLC admitted to our hospital from May 2018 to January 2023 were selected as subjects.The methylation level of SCARA5 was detected by targeted bisulfite sequencing and realtime quantitative methylation-specific polymerase chain reaction ( RQ-MSP ).Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect SCARA5 mRNA levels and Spearman was used to analyze the correlation. Kaplan-Meier survival curve and COX risk proportional model were used to analyze the effect of SCARA5 methylation on prognosis.
Results
The methylation level of SCARA5 in NSCLC tumor tissue was 9.32(7.59,10.80) and 7.45 (6.36,8.55),respectively.SCARA5 mRNA in tumor tissue 3.22(2.86,4.14) was lower than that in paracancer tissue4.01 (3.53,4.46) (P <0.05).SCARA5 hypermethylation (median ≥9.32) at 6 months,9 months,12 months relative dose intensity (relative dose intensity,RDI≥70% in 20 (57.14%),16 (45.71%),13 (19.12%) were lower than those in SCARA5 hypomethyl group 28(82.35%),28(82.35%),24(35.29%) (P<0.05).There were 30 cases (43.48%) with recurrence,and the median relapse-free survival was 21.00months.The follow-up was 28.00months,and 28 cases (40.58%) died.COD analysis showed that SCARA5 methylation was correlated with OS[HR:3.503(95%CI:1.327-9.248)] and DFS[HR:2.393(95%CI:1.075-5.329)] of ACT after NSCLC.The methylation level of SCARA5 in tumor tissue was negatively correlated with the mrna level of ScarA5 (Rho=-0.254, P=0.035).SCARA5 hypermethylated DFS 40.00% was lower than SCARA5 hypomethylated DFS 73.53%,and SCARA5 hypermethylated OS 37.14% was lower than SCARA5 hypomethylated OS 82.35%(P <0.05).
Conclusion
Hypermethylation of SCARA5 in resectable NSCLC after ACT has a poor prognosis,and SCARA5 can be a prognostic indicator of NSCLC.
To analyze the prognostic significance of dead cavity score (VD/VT) in acute respiratory distress syndrome (ARDS).
Methods
A total of 86 ARDS patients admitted to our hospital from March 2021 to March 2024 were selected.49 of them died in hospital in the observation group and 37 survived in the control group.Acute physiological and chronic health score Ⅱ(APACHEⅡ),positive end-expiratory pressure (PEEP) and oxygenation index (PaO2/FiO2) were recorded on the 1st and 3rd day after admission.in-hospital mortality was recorded.Blood gas tests were performed every 6 hours,and VD/VT was calculated using the Harris-Benedict formula (VD/VTHB) and the direct physiological variable estimation formula (VD/VTphys).The association between VD/VTphys,VD/VTHB and mortality was analyzed using restricted cubic splines (RCS).Receiver operating characteristic (ROC) curve was drawn to analyze the area under the curve(AUC) for predicting in-hospital observation in ARDS.
Results
VD/VTphys(0.56±0.04) and (0.59±0.06) on day 1 and day 3 in the death group,VD/VTHB(0.57±0.07),(0.59±0.08) were higher than those of control group (0.60±0.05),(0.63±0.05),VD/VTHB(0.62±0.08),(0.66±0.08) on day 1 and day 3(P<0.05).On day 3,VD/VTphys(0.63±0.05) and VD/VTHB(0.66±0.08) in the observation group were higher than those on day 1,compared with (0.60±0.05) and(0.62±0.08).VD/VTphys on day 3 (0.59±0.06) was higher than that on day 1(0.56±0.04) in control group.Multivariate Logistic regression analysis showed that third dVD/VTphys and VD/VTHB were associated with in-hospital death in ARDS patients (P<0.001).RCS analysis showed that the relationship between VD/VTphys or VD/VTHB and mortality risk at day 3 was non-linear,with a negative correlation when VD/VTHB was below 0.58.After admission,dVD/VTphys and VD/VTHB were added on the basis of dAPACHEⅡ,PEEP and PaO2/FiO2 to improve the predictive value of ARDS hospital death (P<0.05).
Conclusion
Estimation of VD/VT value on the 3rd day after admission can predict the prognosis of ARDS in hospital,which has clinical significance.
To explore the effects of omnidirectional non-blind spot management model under early warning mechanism on hospital stay and occurrence of adverse events in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with respiratory failure (RF).
Methods
All of 129 patients with AECOPD and RF admitted to department of the hospital from January 2022 to January 2024 were selected and randomly divided into observation group (n=65) and control group (n=64)by the single-double number method.The control group was given routine management model while the observation group was given omnidirectional non-blind spot management model under early warning mechanism.The differences in treatment time and hospital stay (ICU treatment time,mechanical ventilation time,hospital stay) were compared between the two groups of patients,and the differences in comfort [Kolcaba General Comfort Questionnaire (GCQ)] and quality of life [St George's Respiratory Questionnaire (SGRQ)] before and after intervention and occurrence of adverse events [ventilator-associated pneumonia(VAP),ventilator dependence (VD),pipeline blockage,mask leakage,asphyxia] during hospitalization were analyzed.
Results
The ICU treatment time,mechanical ventilation time and hospital stay with (16.68±2.01) d,(8.28±1.36)d and (29.44±3.95) d in observation group were shorter than (16.68±2.01) d,(8.28±1.36) d and (29.44±3.95) d in control group (P<0.01).After intervention,the comfort scores of physiology,psychology,society and environment in the two groups were increased compared with those before intervention (P<0.05),and after intervention,the physiological score (18.74±3.04),psychological score (31.88±3.54),social score (27.74±3.68) and environmental comfort score (18.26±2.74) in the observation group were higher than those in the control group (14.28±2.57),(23.69±3.28) and (22.38±3.19),(15.64±2.47) (P<0.05).The scores of respiratory symptoms,activity limitation and disease impact in the two groups were decreased after intervention compared to before treatment (P<0.05),and the respiratory symptom score (37.64±4.21),activity limitation score (36.37±4.64) and disease impact score (38.28±4.97) of the observation group after intervention were lower than those of the control group (40.25±4.85),(36.37±4.64) and (44.37±4.58) (P<0.05).During hospitalization,the incidence rate of total adverse events in observation group with 6.15% was lower compared with 20.31% in control group (P <0.05).
Conclusion
The application of omnidirectional non-blind spot management model under early warning mechanism in AECOPD with RF is helpful for the treatment progress of patients,and can shorten the hospitalization treatment time,control the occurrence of adverse events,and improve the comfort and quality of life.