The association between patella alignment and morphology and knee osteoarthritis.

OBJECTIVE: This study aims to quantitatively assess the relationship between the patella alignment and morphology and knee osteoarthritis (KOA), as well as the kinematics and kinetics of the knee, using gait analysis. METHODS: Eighty age-matched patients with KOA and control subjects were evaluated. Incident radiographic osteoarthritis (iROA) was identified using a Kellgren-Lawrence (KL) grade of ≥ 2. The modified Insall-Salvati ratio (Mod-ISR), patellar tilt angle (PTA), and patella index (PI) were utilized to evaluate the sagittal and transverse alignment of the patella and its morphology, respectively. Regression analyses were conducted to explore associations between patellar measurements and KOA, iROA, kinematics, and kinetics. RESULTS: Significant differences were observed between the control and KOA groups in terms of KL grade, patella alta, abduction angle, and reaction force to the ground (P < 0.05, respectively). Following adjustment for covariates, a significant positive association was found between patella alta and KOA (OR = 0.307, 95%CI: 0.103 to 0.918, P = 0.035). Additionally, a significant negative association was observed between PTA and abduction angle (B = -0.376, 95%CI: -0.751 to -0.002; P = 0.049). The PI exhibited a statistically significant association with log-transformed vertical ground reaction force (B = 0.002, 95%CI: 0.001 to 0.003, P = 0.002). Furthermore, adjustment for covariates did not reveal any significant correlations with other indicators (P > 0.05, respectively). CONCLUSION: This study provides further evidence that proper alignment and morphology of the patella might be associated with maintaining normal biomechanical function. In addition, intervention measures targeting relevant patellar parameters, such as Mod-ISR, PTA, and PI, may positively impact KOA treatment outcomes.

Transcatheter Arterial Chemoembolization Combined with Hepatic Arterial Infusion Chemotherapy Versus Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

In this study, we evaluated the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with hepatic arterial infusion chemotherapy (HAIC) compared to TACE monotherapy for the treatment of unresectable hepatocellular carcinoma (HCC). Relevant studies were systematically searched in PubMed, Embase, Web of Science, and Cochrane Library databases until September 1, 2023. Our analysis included 7 cohort studies encompassing a total of 630 patients. The results demonstrated that the TACE plus HAIC group exhibited significantly improved prognosis compared to the TACE alone group, as evidenced by superior rates of complete response, partial response, progressive disease, objective response rate, and disease control rate. Moreover, the TACE group displayed a lower risk of platelet reduction and vomiting when compared to the TACE plus HAIC group. None of the 7 studies reported any intervention-related mortality. In conclusion, the combination of TACE and HAIC may be recommended as a viable option for patients with unresectable HCC, given its evident enhancements in survival and tumor response rates without significant differences in adverse events when compared to TACE monotherapy. Nevertheless, additional randomized controlled trials and studies involving Western cohorts are warranted to further validate these findings.

Transcatheter Arterial Chemoembolization Combined with Hepatic Arterial Infusion Chemotherapy Versus Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND/AIMS: In this study, we evaluated the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with hepatic arterial infusion chemotherapy (HAIC) compared to TACE monotherapy for the treatment of unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Relevant studies were systematically searched in PubMed, Embase, Web of Science, and Cochrane Library databases until September 1, 2023. Our analysis included 7 cohort studies encompassing a total of 630 patients. RESULTS: The results demonstrated that the TACE plus HAIC group exhibited significantly improved prognosis compared to the TACE alone group, as evidenced by superior rates of complete response, partial response, progressive disease, objective response rate, and disease control rate. Moreover, the TACE group displayed a lower risk of platelet reduction and vomiting when compared to the TACE plus HAIC group. None of the 7 studies reported any intervention-related mortality. CONCLUSION: In conclusion, the combination of TACE and HAIC may be recommended as a viable option for patients with unresectable HCC, given its evident enhancements in survival and tumor response rates without significant differences in adverse events when compared to TACE monotherapy. Nevertheless, additional randomized controlled trials and studies involving Western cohorts are warranted to further validate these findings.

Revealing the Mechanisms of Qilongtian Capsules in the Treatment of Chronic Obstructive Pulmonary Disease Based on Integrated Network Pharmacology, Molecular Docking, and In Vivo Experiments.

The Qilongtian capsule (QLT) is a Chinese patent medicine that has been approved for the treatment of chronic obstructive pulmonary disease (COPD). However, the precise pharmacodynamic material basis and molecular mechanism have not been well illustrated. In this study, we identified the effect of QLT on COPD through a cigarette smoke extract (CSE)/lipopolysaccharide (LPS) induced COPD mice model. The absorption of blood components in QLT were identified using ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Network pharmacology was used to predict the potential targets and therapeutic mechanisms of QLT, which were further validated using in vivo experiments and molecular docking. Pharmacodynamic studies revealed that QLT could ameliorate pulmonary function and pulmonary pathology, reduce collagen fiber accumulation, and attenuate inflammatory responses in mice with CSE/LPS induced COPD. A total of 21 components of QLT absorbed in the blood were detected. Network pharmacology analysis indicated that TNF, IL-6, EGFR, and AKT1 may be the core targets, mainly involving the MAPK signaling pathway. Besides, Sachaloside II, Ginsenoside Rh1, Ginsenoside F1, Rosiridin, and Ginsenoside Rf were the key compounds. Molecular docking results showed that the key components could spontaneously bind to EGFR and MAPK to form a relatively stable conformation. In vivo experiments revealed that QLT could suppress the activation of the EGFR/MAPK signaling pathway, thereby improving lung injury in mice with COPD. Overall, these findings provide evidence for the treatment of COPD with QLT.

Seawater quality criteria derivation and ecological risk assessment for dichlorvos in China.

Dichlorvos (DDVP) is a widely used organophosphorus pesticide (OPP) that has been frequently detected in the marine environment of China. Water quality criteria (WQC) is however not available for this emergent pollutant in the marine environment, which hinders its ecological risk assessment. This study, therefore, screened toxicity values of DDVP and conducted toxicity tests on six marine species to supplement toxicity data. The WQC for DDVP was derived with the species sensitivity distribution (SSD) methodology, based on which the ecological risk of DDVP in the seawater of China was assessed. The results showed that the recommended short-term (SWQC) and long-term water quality criteria (LWQC) for DDVP were 1.47 and 0.0521 µg/L, respectively. Most marine waters of China showed low or negligible risk (HQ < 1, ORP < 2 %), whereas some estuarine waters warrant further concern due to higher risk. This study provides the scientific basis for seawater quality standard formulation and ecological risk management for DDVP.

Prognostic value of cardiopulmonary exercise test in patients with acute myocardial infarction after percutaneous coronary intervention.

To determine the independent risk factors of cardiopulmonary exercise test (CPET) parameters related to adverse prognostic events within 5 years in patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI), and establish a prediction model for the occurrence of adverse events within 5 years to provide a reference for cardiac rehabilitation training. From August 2015 to December 2021, patients who underwent PCI for AMI and completed CPET within 1-2 weeks after surgery before discharge from the Department of Cardiovascular Medicine of Zhengzhou Central Hospital Affiliated to Zhengzhou University, Henan Provincial Hospital of Traditional Chinese Medicine, and Anyang District Hospital were selected as participants. Univariate and multivariate analyses were used to screen for independent risk factors associated with 5-year adverse events. Feature importance was interpreted using SHapley Additive exPlanations (SHAP), and a logistic regression model was established for prediction. A receiver operating characteristic (ROC) curve was constructed to evaluate the performance of the prediction model. Calibration was assessed by the Hosmer-Lemeshow test and the calibration curve. In total, 375 patients met the inclusion criteria. Based on whether adverse events occurred during the 5-year follow-up period, the patients were divided into two groups: the event group (n = 53) and the non-event group (n = 322). Peak oxygen uptake (peakVO2), carbon dioxide ventilation equivalent slope (VE/VCO2slop), and peak end-tidal carbon dioxide partial pressure (PETCO2) were three independent risk factors for re-acute myocardial infarction (re-AMI), heart failure (HF), and even death after PCI for AMI (P < 0.05). The SHAP plots demonstrated that the significant contributors to model performance were related to peakVO2, VE/VCO2slop, and PETCO2. The risk of adverse events was significantly reduced when the peakVO2 was ≥ 20 mL/kg/min and the VE/VCO2slop was < 33. The ROC curves of the three models were drawn, including the no-event and event groups, re-AMI group, and HF group, which performed well, with AUC of 0.894, 0.760, and 0.883, respectively. The Hosmer-Lemeshow test showed that the three models were a good fit (P > 0.05). The calibration curve of the three models was close to the ideal diagonal lines. CPET parameters can predict the prognosis of adverse events within 5 years after PCI in patients with AMI and provide a theoretical basis for cardiac rehabilitation training.

Comparison of totally robotic and totally laparoscopic gastrectomy for gastric cancer: a propensity score matching analysis.

BACKGROUND: With the improvements in laparoscopic or robotic surgical techniques and instruments, a growing number of surgeons have attempted to complete all digestive tract reconstruction intracorporeally; these procedures include totally robotic gastrectomy (TRG) and totally laparoscopic gastrectomy (TLG). This study aimed to evaluate the safety and feasibility of the TRG and compare the short-term outcomes of the TRG and TLG in patients with gastric cancer. METHODS: Between January 2018 and June 2023, 346 consecutive patients who underwent TRG or TLG at a high-volume academic gastric cancer specialty center were included. 1:1 propensity score matching (PSM) was performed to reduce confounding bias. The surgical outcomes, postoperative morbidity, and surgical burden were compared in PSM cohort. RESULTS: After PSM, a well-balanced cohort of 194 patients (97 in each group) was included in the analysis. The total operation time of the TRG group was significantly longer than that of the TLG group (244.9 vs. 213.0 min, P < 0.001). There was no significant difference in the effective operation time between the 2 groups (217.8 vs. 207.2 min, P = 0.059). The digestive tract reconstruction time of the TRG group was significantly shorter than that of the TLG group (39.4 vs. 46.7 min, P < 0.001). The mean blood loss in the TRG group was less than that in the TLG group (101.1 vs. 126.8 mL, P = 0.014). The TRG group had more retrieved lymph nodes in the suprapancreatic area than that in the TLG group (16.6 vs 14.2, P = 0.002). The TRG group had a lower surgery task load index (38.9 vs. 43.1, P < 0.001) than the TLG group. No significant difference was found in terms of postoperative morbidity between the 2 groups (14.4% vs. 16.5%, P = 0.691). CONCLUSION: This study demonstrated that TRG is a safe and feasible procedure, and is preferable to TLG in terms of invasion and ergonomics. The TRG may maximize the superiority of robotic surgical systems and embodies the theory of minimally invasive surgery.

Pan-cancer single-cell landscape of drug-metabolizing enzyme genes.

OBJECTIVE: Varied expression of drug-metabolizing enzymes (DME) genes dictates the intensity and duration of drug response in cancer treatment. This study aimed to investigate the transcriptional profile of DMEs in tumor microenvironment (TME) at single-cell level and their impact on individual responses to anticancer therapy. METHODS: Over 1.3 million cells from 481 normal/tumor samples across 9 solid cancer types were integrated to profile changes in the expression of DME genes. A ridge regression model based on the PRISM database was constructed to predict the influence of DME gene expression on drug sensitivity. RESULTS: Distinct expression patterns of DME genes were revealed at single-cell resolution across different cancer types. Several DME genes were highly enriched in epithelial cells (e.g. GPX2, TST and CYP3A5 ) or different TME components (e.g. CYP4F3 in monocytes). Particularly, GPX2 and TST were differentially expressed in epithelial cells from tumor samples compared to those from normal samples. Utilizing the PRISM database, we found that elevated expression of GPX2, CYP3A5 and reduced expression of TST was linked to enhanced sensitivity of particular chemo-drugs (e.g. gemcitabine, daunorubicin, dasatinib, vincristine, paclitaxel and oxaliplatin). CONCLUSION: Our findings underscore the varied expression pattern of DME genes in cancer cells and TME components, highlighting their potential as biomarkers for selecting appropriate chemotherapy agents.

MEG3 in hematologic malignancies: from the role of disease biomarker to therapeutic target.

Maternally expressed gene 3 ( MEG3 ) is a noncoding RNA that is known as a tumor suppressor in solid cancers. Recently, a line of studies has emphasized its potential role in hematological malignancies in terms of tumorigenesis, metastasis, and drug resistance. Similar to solid cancers, MEG3 can regulate various cancer hallmarks via sponging miRNA, transcriptional, or posttranslational regulation mechanisms, but may regulate different key elements. In contrast with solid cancers, in some subtypes of leukemia, MEG3 has been found to be upregulated and oncogenic. In this review, we systematically describe the role and underlying mechanisms of MEG3 in multiple types of hematological malignancies. Particularly, we highlight the role of MEG3 in drug resistance and as a novel therapeutic target.

Morphology and transverse alignment of the patella have no effect on knee gait characteristics in healthy Chinese adults over the age of 40 years.

Background: The influence of patella morphology and horizontal alignment on knee joint kinematics and kinetics remains uncertain. This study aimed to assess patella morphology and transverse alignment in relation to knee kinetics and kinematics in individuals without knee conditions. A secondary objective was to investigate the impact of femur and tibia alignment and shape on knee gait within this population. Patients and methods: We conducted a prospective collection of data, including full-leg anteroposterior and skyline X-ray views and three-dimensional gait data, from a cohort comprising 54 healthy individuals aged 40 years and older. Our study involved correlation and logistic regression analyses to examine the influence of patella, femur, and tibia morphology and alignment on knee gait. Results: The patellar tilt angle or the patella index did not show any significant relationships with different aspects of gait in the knee joint, such as velocity, angle, or moment (p > 0.05, respectively). Using multivariate logistic regression analysis, we found that the tibiofemoral angle and the Q angle both had a significant effect on the adduction angle (OR = 1.330, 95%CI 1.033-1.711, p = 0.027; OR = 0.475, 95%CI 0.285-0.792, p = 0.04; respectively). The primary variable influencing the knee adduction moment was the tibiofemoral angle (OR = 1.526, 95% CI 1.125-2.069, p = 0.007). Conclusion: In healthy Chinese individuals aged over 40, patella morphology and transverse alignment do not impact knee gait. However, the femoral-tibial angle has a big impact on the knee adduction moment.

Corrigendum: Radiomic machine learning and external validation based on 3.0T mpMRI for prediction of intraductal carcinoma of prostate with different proportion.

[This corrects the article DOI: 10.3389/fonc.2022.934291.].

Qualitative and Quantitative Measures in the Infrapatellar Fat Pad in Older Adults: Associations with Knee Pain, Radiographic Osteoarthritis, Kinematics, and Kinetics of the Knee.

RATIONALE AND OBJECTIVES: The purpose of this study is to delineate cross-sectional associations between qualitative and quantitative measures of the infrapatellar fat pad (IPFP) and knee symptoms, structure, kinematics, and kinetics in older adults. METHODS: Ninety eligible subjects (90 knees, mean age 54.0 years, 68.9% female) were examined at our center. We used T2-weighted fat-suppressed magnetic resonance imaging (MRI) to evaluate signal intensity alteration, maximum sagittal area, and depth of the IPFP. Symptomatic osteoarthritis (SOA) was a pain subscale score greater than 0 on the Western Ontario McMaster Osteoarthritis Index. A Kellgren-Lawrence grade ≥ 2 identified incident radiographic osteoarthritis (iROA). Three-dimensional gait data were employed to analyze knee joint kinematics and kinetics. Correlation and regression analyzes assessed associations between IPFP measurements and SOA, iROA, kinematics, and kinetics. RESULTS: There were strong and positive associations between IPFP signal intensity alteration and both SOA and iROA in multivariable regression analyzes [OR (95% CI): 2.849 (1.440 to 5.636), 2.356 (1.236 to 4.492), respectively]. Conversely, a significant negative correlation was observed between IPFP maximum area and flexion angle [B (95%CI): - 1.557 (-2.549 to -0.564)]. Moreover, adjusting for covariates did not reveal any significant correlation between IPFP parameters and other indicators (P > 0.05, respectively). CONCLUSION: IPFP signal intensity alteration and area were associated with knee clinical symptoms, structural abnormalities, and flexion angle in adults over 40, respectively. These findings suggest that IPFP may be a crucial imaging biomarker in early and middle knee osteoarthritis.

Swept coded aperture real-time femtophotography.

Single-shot real-time femtophotography is indispensable for imaging ultrafast dynamics during their times of occurrence. Despite their advantages over conventional multi-shot approaches, existing techniques confront restricted imaging speed or degraded data quality by the deployed optoelectronic devices and face challenges in the application scope and acquisition accuracy. They are also hindered by the limitations in the acquirable information imposed by the sensing models. Here, we overcome these challenges by developing swept coded aperture real-time femtophotography (SCARF). This computational imaging modality enables all-optical ultrafast sweeping of a static coded aperture during the recording of an ultrafast event, bringing full-sequence encoding of up to 156.3 THz to every pixel on a CCD camera. We demonstrate SCARF's single-shot ultrafast imaging ability at tunable frame rates and spatial scales in both reflection and transmission modes. Using SCARF, we image ultrafast absorption in a semiconductor and ultrafast demagnetization of a metal alloy.

Long-term oncological outcomes of robotic versus laparoscopic gastrectomy for gastric cancer: multicentre cohort study.

BACKGROUND: The aim of this multicentre cohort study was to compare the long-term oncological outcomes of robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) for patients with gastric cancer. METHODS: Patients with gastric cancer who underwent radical gastrectomy by robotic or laparoscopic approaches from 1 March 2010 to 31 December 2018 at 10 high-volume centres in China were selected from institutional databases. Patients receiving RG were matched 1 : 1 by propensity score with patients undergoing LG. The primary outcome was 3-year disease-free survival. Secondary outcomes were overall survival and disease recurrence. RESULTS: Some 2055 patients who underwent RG and 4309 patients who had LG were included. The propensity score-matched cohort comprised 2026 RGs and 2026 LGs. Median follow-up was 41 (i.q.r. 39-58) months for the RG group and 39 (38-56) months for the LG group. The 3-year disease-free survival rates were 80.8% in the RG group and 79.5% in the LG group (log rank P = 0.240; HR 0.92, 95% c.i. 0.80 to 1.06; P = 0.242). Three-year OS rates were 83.9 and 81.8% respectively (log rank P = 0.068; HR 0.87, 0.75 to 1.01; P = 0.068) and the cumulative incidence of recurrence over 3 years was 19.3% versus 20.8% (HR 0.95, 0.88 to 1.03; P = 0.219), with no difference between groups. CONCLUSION: RG and LG in patients with gastric cancer are associated with comparable disease-free and overall survival.

260 fs, 403 W coherently combined fiber laser with precise high-order dispersion management.

An ultrafast fiber laser system comprising two coherently combined amplifier channels is reported. Within this system, each channel incorporates a rod-type fiber power amplifier, with individual operations reaching approximately 233 W. The active-locking of these coherently combined channels, followed by compression using gratings, yields an output with a pulse energy of 504 µJ and an average power of 403 W. Exceptional stability is maintained, with a 0.3% root mean square (RMS) deviation and a beam quality factor M2 < 1.2. Notably, precise dispersion management of the front-end seed light effectively compensates for the accumulated high-order dispersion in subsequent amplification stages. This strategic approach results in a significant reduction in the final output pulse duration for the coherently combined laser beam, reducing it from 488 to 260 fs after the gratings compressor, while concurrently enhancing the energy of the primary peak from 65% to 92%.

Tumor-infiltrating mast cells stimulate ICOS+ regulatory T cells through an IL-33 and IL-2 axis to promote gastric cancer progression.

INTRODUCTION: In solid tumors, regulatory T cell (Treg) and mast cell perform different roles depending on the microenvironment. Nevertheless, mast cell and Treg-mediated interactions in gastric cancer (GC) are unclear, as are their regulation, function, and clinical significance. OBJECTIVE: The present study demonstrated the mechanism of tumor-infiltrating mast cells stimulating ICOS+ regulatory T cells via the IL-33/IL-2 axis to promote the growth of gastric cancer. METHODS: Analyses of 98 patients with GC were conducted to examine mast cell counts, ICOS+ Tregs, and the levels of IL-33 or IL-2. Isolated ICOS+ Treg and CD8+ T cell were stimulated, cultured and tested for their functional abilities in vitro and in vivo. RESULTS: GC patients exhibited a significantly more production of IL-33 in tumors. Mast cell stimulated by tumor-derived IL-33 exhibited a prolonged lifespan through IL-33 mediated inhibition of apoptosis. Moreover, mast cells stimulated by tumor-derived IL-33 secreted IL-2, which induced Treg expansion. These inducible Tregs displayed an activated immunosuppressive phenotype with positive expression for the inducible T cell co-stimulator (ICOS). In vitro, IL-2 from IL to 33-stimulated mast cells induced increased numbers of ICOS+ Tregs with increased immunosuppressive activity against proliferation and effector function of CD8+ T cell. In vivo, ICOS+ Tregs were treated with anti-IL-2 neutralizing antibody followed by co-injection with CD8+ T cells in GC mouse model, which showed an increased CD8+ T cell infiltration and effector molecules production, meanwhile tumor growth and progression were inhibited. Besides, reduction in GC patient survival was associated with tumor-derived ICOS+ Tregs. CONCLUSION: Our results highlight a crosstalk between GC-infiltrating mast cells and ICOS+ Tregs and provide a novel mechanism describing ICOS+ Treg expansion and induction by an IL-33/mast cell/IL-2 signaling axis in GC, and also provide functional evidence that the modulation of this immunosuppressive pathway can attenuate GC-mediated immune tolerance.

Meta-analysis of the hazards of microplastics in freshwaters using species sensitivity distributions.

The environmental hazards of microplastics have raised concerns about their potential ecological risks. However, our understanding of the true risks may be limited because most laboratory studies used pristine microplastics. Here, we analyzed the available literature about ecotoxicological effects of microplastics, including weathered microplastics in particular, on freshwater biota and performed probabilistic species sensitivity distributions. The predicted no-effect concentrations for pristine microplastics were lower than those for weathered microplastics, both in mass concentration (6.1 and 4.8 × 102 µg/L) and number concentration (2.6 × 104 and 2.0 × 106 part/m3). In addition, the toxicological studies on microplastics contains often inconsistent and inconclusive information due to the complexity of the microplastics and the employed exposure conditions. The available data for Daphnia magna and Danio rerio was analyzed in detail to understand the effects of microplastic size, shape and polymer type on their ecotoxicity. Microplastic size was the biggest driving factor, followed by shape and polymer type. There was a tendency for increasing toxicity with smaller size, however, a high variability of effect data was observed for small microplastics. This study provided further insights into the effect thresholds for ecological risk assessment of microplastics and the effects of microplastic characteristics on toxicity.

Single-shot observation of nonlinear pulse splitting in a Kerr medium.

We report single-shot, time-resolved observation of self-steepening and temporal splitting of near-infrared, 50 fs, micro-joule pulses propagating nonlinearly in flint (SF11) glass. A coherent, smooth-profiled, 60-nm-bandwidth probe pulse that propagated obliquely to the main pulse through the Kerr medium recorded a time sequence of longitudinal projections of the main pulse's induced refractive index profile in the form of a phase-shift "streak," in which frequency-domain interferometry recovered with ∼10 fs temporal resolution. A three-dimensional simulation based on a unidirectional pulse propagation equation reproduced observed pulse profiles.

Temporal resolution of ultrafast compressive imaging using a single-chirped optical probe.

Ultrafast compressive imaging captures three-dimensional spatiotemporal information of transient events in a single shot. When a single-chirped optical probe is applied, the temporal information is obtained from the probe modulated in amplitude or phase using a direct frequency-time mapping method. Here, we extend the analysis of the temporal resolution of conventional one-dimensional ultrafast measurement techniques such as spectral interferometry to that in three-dimensional ultrafast compressive imaging. In this way, both the amplitude and phase of the probe are necessary for a full Fourier transform method, which obtains temporal information with an improved resolution determined by probe spectral bandwidth. The improved temporal resolution potentially enables ultrafast compressive imaging with an effective imaging speed at the quadrillion-frames-per-second level.

[Mechanism of Qilongtian Capsules in treatment of acute lung injury based on network pharmacology prediction and experimental validation].

This study aimed to explore the mechanism of Qilongtian Capsules in treating acute lung injury(ALI) based on network pharmacology prediction and in vitro experimental validation. Firstly, UPLC-Q-TOF-MS/MS was used to analyze the main chemical components of Qilongtian Capsules, and related databases were used to obtain its action targets and ALI disease targets. STRING database was used to build a protein-protein interaction(PPI) network. Metascape database was used to conduct enrichment analysis of Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG). AutoDock software was used to perform molecular docking verification on the main active components and key targets. Then, the RAW264.7 cells were stimulated with lipopolysaccharide(LPS) for in vitro experiments. Cell viability was measured by MTT and ROS level was measured by DCFH-DA. NO content was measured by Griess assay, and IL-1ß, IL-6, and TNF-α mRNA expression was detected by RT-PCR. The predicted targets were preliminarily verified by investigating the effect of Qilongtian Capsules on downstream cytokines. Eighty-four compounds were identified by UPLC-Q-TOF-MS/MS. Through database retrieval, 44 active components with 589 target genes were screened out. There were 560 ALI disease targets, and 65 intersection targets. PPI network topology analysis revealed 10 core targets related to ALI, including STAT3, JUN, VEGFA, CASP3, and MMP9. KEGG enrichment analysis showed that Qilongtian Capsules mainly exerted an anti-ALI effect by regulating cancer pathway, AGE-RAGE, MAPK, and JAK-STAT signaling pathways. The results of molecular docking showed that the main active components in Qilongtian Capsules, including crenulatin, ginsenoside F_1, ginsenoside Rb_1, ginsenoside Rd, ginsenoside Rg_1, ginsenoside Rg_3, notoginsenoside Fe, notoginsenoside G, notoginsenoside R_1, notoginsenoside R_2, and notoginsenoside R_3, had good binding affinities with the corresponding protein targets STAT3, JUN, VEGFA, CASP3, and MMP9. Cellular experiments showed that Qilongtian Capsules at 0.1, 0.25, and 0.5 mg·mL~(-1) reduced the release of NO, while Qilongtian Capsules at 0.25 and 0.5 mg·mL~(-1) reduced ROS production, down-regulated mRNA expression of IL-1ß, IL-6, TNF-α, and inhibited the inflammatory cascade. In summary, Qilongtian Capsules may exert therapeutic effects on ALI through multiple components and targets.