Up-regulation of PRKDC was associated with poor renal dysfunction after renal transplantation: A multi-centre analysis.

Renal transplantation is the only efficacious treatment for end-stage kidney disease. However, some people have developed renal insufficiency after transplantation, the mechanisms of which have not been well clarified. Previous studies have focused on patient factors, while the effect of gene expression in the donor kidney on post-transplant renal function has been less studied. Donor kidney clinical data and mRNA expression status were extracted from the GEO database (GSE147451). Weight gene co-expression network analysis (WGCNA) and differential gene enrichment analysis were performed. For external validation, we collected data from 122 patients who accepted renal transplantation at several hospitals and measured the level of target genes by qPCR. This study included 192 patients from the GEO data set, and 13 co-expressed genes were confirmed by WGCNA and differential gene enrichment analysis. Then, the PPI network contained 17 edges as well as 12 nodes, and four central genes (PRKDC, RFC5, RFC3 and RBM14) were identified. We found by collecting data from 122 patients who underwent renal transplantation in several hospitals and by multivariate logistic regression that acute graft-versus-host disease postoperative infection, PRKDC [Hazard Ratio (HR) = 4.44; 95% CI = [1.60, 13.68]; p = 0.006] mRNA level correlated with the renal function after transplantation. The prediction model constructed had good predictive accuracy (C-index = 0.886). Elevated levels of donor kidney PRKDC are associated with renal dysfunction after transplantation. The prediction model of renal function status for post-transplant recipients based on PRKDC has good predictive accuracy and clinical application.

Clinical profiles differ in IgG4-related disease with and without allergy: a large case-control study in China.

OBJECTIVES: This study aimed to elucidate different clinical profiles in IgG4-related disease (IgG4-RD) with and without allergy. METHODS: Four hundred and thirty-four patients diagnosed with IgG4-RD at Peking University People's Hospital were included. Clinical and treatment options-based relapse data were collected and compared between IgG4-RD patients with and without allergy. RESULTS: Among these patients, 214 (49.3%) had allergic diseases. Most of the IgG4-RD patients with allergy had initial involved organs directly exposed to ambient air and their allergic symptoms occurred mostly before or at IgG4-RD disease onset. Compared with IgG4-RD patients without allergy, allergic patients had almost equal sex ratio, more organ involvement, earlier ages of disease onset and diagnosis, longer disease duration, higher incidence of dacryoadenitis, sialadenitis, lymphadenopathy, paranasal sinus and lung lesions. Higher serum IgG4, IgE and IgG4/IgG ratio, lower serum C3 complement 3 (C3) and C4, and higher incidence of eosinophilia were also found in IgG4-RD patients with allergy. Furthermore, allergy may increase relapse rate and shorten relapse-free survival time in IgG4-RD patients treated with glucocorticoids only, whereas combination therapy of glucocorticoids and immunosuppressants could improve treatment outcome. CONCLUSIONS: Allergy leads to disparities in clinical profiles in IgG4-RD patients. Allergy could result in higher relapse rate and shorten relapse-free survival time in patients receiving glucocorticoids only.

Near-infrared fluorescence imaging of thoracic duct in minimally invasive esophagectomy.

Chylothorax is a serious complication after esophagectomy and there are unmet needs for new intraoperative navigation tools to reduce its incidence. The aim of this study is to explore the feasibility and effectiveness of near-infrared fluorescence imaging (NIR-FI) with indocyanine green (ICG) to identify thoracic ducts (TDs) and chyle leakage during video-assisted thoracoscopic esophagectomy. We recruited 41 patients who underwent thoraco-laparoscopic minimally invasive esophagectomy (MIE) for esophageal cancer in this prospective, open-label, single-arm clinical trial. ICG was injected into the right inguinal region before operations, after which TD anatomy and potential chyle leakage were checked under the near-infrared fluorescence intraoperatively. In 38 of 41 patients (92.7%) using NIR-FI, TDs were visible in high contrast. The mean signal-to-background ratio (SBR) value of all fluorescent TDs was 3.05 ± 1.56. Fluorescence imaging of TDs could be detected 0.5 hours after ICG injection and last up to 3 hours with an acceptable SBR value. The optimal observation time window is from about 1 to 2 hours after ICG injection. Under the guidance of real-time NIR-FI, three patients were found to have chylous leakage and the selective TD ligations were performed intraoperatively. No patient had postoperative chylothorax. NIR-FI with ICG can provide highly sensitive and real-time assessment of TDs as well as determine the source of chyle leakage, which might help reduce TD injury and direct selective TD ligation. It could be a promising navigation tool to reduce the incidence of chylothorax after minimally invasive esophagectomy.

Stepwise evolutionary genomics of early-stage lung adenocarcinoma manifesting as pure, heterogeneous and part-solid ground-glass nodules.

BACKGROUND: This study was designed to unravel the genomic landscape and evolution of early-stage subsolid lung adenocarcinomas (SSN-LUADs) manifesting as pure ground-glass nodules (pGGNs), heterogeneous ground-glass nodules (HGGNs) and part-solid nodules (PSNs). METHODS: Samples subjected to either broad-panel next-generation sequencing (NGS) or whole-exome sequencing (WES) were included. Clinicopathologic and genomic features were compared among pGGN, HGGN and PSN, while tumour evolutionary trajectories and mutational signatures were evaluated in the entire cohort. RESULTS: In total, 247 SSN-LUAD samples subjected to broad-panel NGS and 125 to WES were identified. Compared with PSNs, HGGNs had significantly lower tumour mutation count (P < 0.001), genomic alteration count (P < 0.001), and intra-tumour heterogeneity (P = 0.005). Statistically significant upward trends were observed in alterations involving driver mutations and oncogenic pathways from pGGNs to HGGNs to PSNs. EGFR mutation was proved to be a key early event in the progression of SSN-LUADs, with subsequently two evolutionary trajectories involving either RBM10 or TP53 mutation in the cancer-evolution models. CONCLUSIONS: This study provided evidence for unravelling the previously unknown genomic underpinnings associated with SSN-LUAD evolution from pGGN to HGGN to PSN, proving that HGGN was an intermediate SSN form between pGGN and PSN genetically.

Clinical characteristics of IgG4-related respiratory disease patients: a large Chinese cohort study.

OBJECTIVES: IgG4-related disease (IgG4-RD) is an autoimmune disorder and frequently involves multiple organs. The respiratory tract is one of the most frequently affected sites. In this study, we aimed to compare the demographic and clinical characteristics between IgG4 related respiratory disease (IgG4-RRD+) and extra-thoracic IgG4-related disease (IgG4-RRD-) in a large cohort. METHODS: A total of 448 cases of IgG4-RD (104 IgG4-RRD+ patients and 344 IgG4-RRD- patients) diagnosed at Peking University People's Hospital during 2003 to 2020 were included in our study. Patients' demographic data, clinical characteristics, laboratory parameters and imaging features were analysed. RESULTS: IgG4-RRD+ patients had an older age at disease onset and diagnosis. Multiorgan involvement and hypocomplementaemia were more common in IgG4-RRD+. Besides, the level of ESR, IgG and IgG4 were higher in IgG4-RRD+ patients. In IgG4-RRD+ group, salivary gland, lacrimal gland, lymph nodes, biliary system and kidney were more commonly involved than those in the IgG4-RRD- group. Also, more organ involvement eosinophilia and biliary involvement were independent risk factors for the development of IgG4-RRD+. CONCLUSIONS: Our study revealed demographic, clinical and laboratory differences between the two phenotypes, in addition to describing the imaging features of IgG4-RRD+, which will be helpful for understanding of the disease.

Clinical features of IgG4-related retroperitoneal fibrosis among 407 patients with IgG4-related disease: a retrospective study.

OBJECTIVES: IgG4-related disease (IgG4-RD) is recently recognized as a fibro-inflammatory condition featured by tumefactive lesions in multiple organs, and the retroperitoneum is one of the common involved sites. We undertook this study to compare detailed demographic, clinical and laboratory characteristics of IgG4-RD patients with retroperitoneum lesion (IgG4-RD RPF+) and retroperitoneum free IgG4-RD (IgG4-RD RPF-) in a large cohort. METHODS: We carried out a retrospective review of the medical records of 407 cases of IgG4-RD diagnosed at Peking University People's Hospital between March 2009 and May 2019. RESULTS: Among 407 patients, 58 had retroperitoneum affected. As compared with IgG4-RD RPF- patients, IgG4-RD RPF+ patients showed older age at disease onset and diagnosis. IgG4-RD RPF+ group involved more male patients. In terms of organ involvement, IgG4-RD RPF+ group was more frequently presented with kidney involvement, while salivary gland, lacrimal gland and pancreas were more prominent in the IgG4-RD RPF- group. In addition, the CRP, ESR level and creatinine level were significantly higher in IgG4-RD RPF+ patients, and hypocomplementemia were more common in this group. CONCLUSION: We have revealed demographic, clinical and laboratory differences between IgG4-RD RPF+ and RPF- patients, which indicated potential differences in pathogenesis and important implications for the diagnosis and management of these two phenotypes.

Salivary gland involvement disparities in clinical characteristics of IgG4-related disease: a retrospective study of 428 patients.

OBJECTIVES: IgG4-related disease (IgG4-RD) has recently been recognized as a fibro-inflammatory condition featuring tumefactive lesions in multiple organs, and the salivary gland is one of the most commonly involved sites. We undertook this study to compare detailed demographic, clinical and laboratory characteristics of IgG4-RD patients with salivary gland lesions (IgG4-RD SG+) and salivary-gland-free IgG4-RD (IgG4-RD SG-) in a large cohort. METHODS: We carried out a retrospective review of the medical records of 428 cases of IgG4-RD diagnosed at Peking University People's Hospital between March 2006 and May 2018. RESULTS: Among 428 patients, 249 had salivary glands that were affected. IgG4-RD SG+ patients showed younger age at disease onset and diagnosis, and a longer interval between symptom onset and diagnosis. The IgG4-RD SG+ group involved more female patients, and allergic diseases were more common in this group. In terms of organ involvement, the IgG4-RD SG+ group were more frequently presented with lacrimal gland involvement, while lymph node, retroperitoneal fibrosis, pancreas, biliary system, kidney and aorta were more prominent in the IgG4-RD SG- group. In addition, the serum IgG4 level, IgG4/IgG ratio and IgE level were significantly higher in IgG4-RD SG+ patients. Patients with eosinophilia were more common in the IgG4-RD SG+ group, while elevated ESR, CRP and positive ANA were more common in the IgG4-RD SG- group. CONCLUSION: We have revealed demographic, clinical and laboratory differences between IgG4-RD SG+ and SG- patients, which indicated potential differences in pathogenesis and important implications for the diagnosis and management of these two phenotypes.

Relapse predictors and serologically unstable condition of IgG4-related disease: a large Chinese cohort.

OBJECTIVES: Patients with IgG4-related disease (IgG4-RD) typically respond well to initial glucocorticoid therapy, but always relapse with tapered or maintenance dosage of steroid. We aimed to identify the risk factors for relapse of IgG4-RD and explore the impact of active intervention on the serologically unstable condition. METHODS: We performed a retrospective study of 277 IgG4-RD patients at Peking University People's Hospital from February 2012 through February 2019. They were all followed for >4 months. The primary outcome was patient relapse. Data on recurrence of IgG4-RD symptoms, laboratory and image findings were recorded, along with information on treatment in the serologically unstable condition. RESULTS: The cumulative relapse rate was 12.86%, 27.84% and 36.1% at 12, 24 and 36 months, respectively. Younger age at onset, younger age at diagnosis, longer time from diagnosis to treatment and history of allergy were associated with relapse. Identified independent risk factors were longer time from diagnosis to treatment and history of allergy. When serum IgG4 level was 20%, 50% or 100% higher than that of the remission period, similar percentages of patients finally relapsed, regardless of whether they were in the immunosuppression intensified or non-intensified group. Median duration from serum IgG4 level instability to relapse in the intensified and non-intensified group was not statistically different. CONCLUSION: The risk factors of relapse were longer time from diagnosis to treatment and history of allergy. Intervention in the serologically unstable condition was not helpful for reducing relapse rate.

Development and validation of a nomogram for predicting cancer-specific survival of surgical resected stage I-II adenosquamous carcinoma of the lung.

OBJECTIVES: Primary lung adenosquamous carcinoma (ASC) is a rare cancer subtype and has a poor prognosis. The prognostic factors for resected early-stage ASC remain unclear. We aimed to develop a nomogram to predict lung cancer-specific survival (LCSS) of patients undergoing surgical resection for stage I-II ASC. METHODS: Data of patients undergoing resection for stage I-II ASC and diagnosed between 2004-2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. All the included patients were randomized at a 7:3 ratio into a training and a validation cohort. We selected and integrated significant prognostic factors based on competing for risk regression to build a nomogram. The performance of the nomogram was evaluated using Harrell's concordance index (C-index) and calibration plots. RESULTS: A total of 988 patients (530 men and 458 women) undergoing surgical resection for stage I-II ASC were identified and randomized into a training (692, 70%) cohort and a validation cohort (296, 30%). The baseline characteristics were similar in the training and validation cohorts. Age, T stage, N stage, and the number of examined lymph nodes were independent prognostic factors for LCSS and were used in the nomogram. The calibration plots showed that the 3- and 5-year LCSS probabilities were consistent between the nomogram prediction and the actual observation. The C-index of the nomogram was 0.671 (95%CI: 0.618-0.724) and 0.635 (95%CI: 0.557-0.713) in the training cohort and validation cohort, respectively. We developed a risk classification system based on the nomogram to stratify patients into high- and low-risk of cancer-specific death groups. Patients with a similar risk shared similar prognostic prediction regardless of the stage category and patients with the same risk shared similar prognoses despite the different stage category. CONCLUSIONS: We developed a competing risk nomogram to reliably predict cancer-specific survival of patients undergoing surgical resection for stage I-II ASC. The nomogram might be a useful tool to identify patients undergoing surgical resection for ASC who could be suitable candidates for adjuvant chemotherapy.

AZD5153 Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo.

BACKGROUNDS/AIMS: Bromodomain-containing protein 4 (BRD4) overexpression participates in prostate cancer progression by enhancing the transcriptional activity and expression of several key oncogenes. AZD5153 is a novel BRD4 inhibitor. METHODS: Prostate cancer cells were treated with AZD5153. Cell survival was tested by MTT assay and clonogenicity assay. Cell proliferation was tested by [H3] DNA incorporation assay. Cell apoptosis was tested by caspase-3/-9 activity assay, Histone DNA ELISA assay, Annexin V FACS assay and TUNEL staining assay. Cell cycle progression was tested by propidium iodide (PI) FACS assay. Signaling was tested by Western blotting assay. The nude mice PC-3 xenograft model was applied to test AZD5153's activity in vivo. RESULTS: AZD5153 inhibited proliferation and survival of established and primary prostate cancer cells. AZD5153 induced apoptosis activation and cell cycle arrest in prostate cancer cells. AZD5153 was non-cytotoxic to the prostate epithelial cells. AZD5153 downregulated BRD4 targets (cyclin D1, Myc, Bcl-2, FOSL1 and CDK4) in PC-3 and primary prostate cancer cells. Further studies show that AKT could be the primary resistance factor of AZD5153. Pharmacological inhibition or genetic depletion of AKT induced BRD4 downregulation, sensitizing AZD5153-induced cytotoxicity in PC-3 cells. In vivo, AZD5153 oral administration inhibited PC-3 xenograft tumor growth in nude mice. Its anti-tumor activity was further enhanced with co-treatment of the AKT specific inhibitor MK-2206. CONCLUSION: Together, our results indicate a promising therapeutic value of the novel BRD4 inhibitor AZD5153 against prostate cancer cells.

GREM1 knockdown regulates the proliferation, apoptosis and EMT of benign prostatic hyperplasia by suppressing the STAT3/c-Myc signaling.

BACKGROUND: Gremlin 1 (GREM1) has been reported to be highly expressed in prostate hyperplasia tissues. However, the role and molecular mechanism of GREM1 in benign prostatic hyperplasia (BPH) is still unclear. METHODS: In this study, expression of GREM1 in BPH-1 cells was detected by western blot assay. Cell counting kit-8 assay was performed to assess cell proliferation. Flow cytometry and western blot were used to assess cell apoptosis and cell cycle. The EMT process was detected by western blot assay and immunofluorescence staining. In addition, colivelin was used as a STAT3 activator and the expressions of STAT3/c-Myc signaling were assessed by western blot assay. RESULTS: The data showed that GREM1 silencing inhibited BPH-1 cell proliferation and promoted cell apoptosis. Moreover, GREM1 silencing repressed the cell cycle progression and the development of EMT. In addition, knockdown of GREM1 suppressed the expression of the STAT3/c-Myc signaling in BPH-1 cells and colivelin treatment rehabilitated this signaling. Moreover, c-Myc overexpression or colivelin reversed the effects of GREM1 silencing on BPH-1 cell proliferation, cell apoptosis, cell cycle, as well as EMT. CONCLUSION: To sum up, GREM1 silencing may alleviate the BPH progress by inhibiting the STAT3/c-Myc signaling.

[Retracted] Human HLA­F adjacent transcript 10 promotes the formation of cancer initiating cells and cisplatin resistance in bladder cancer.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the cellular morphological data in Fig. 1C, the immunofluorescence data shown in Fig. 1E, and certain of the scratch­wound assay data shown in Fig. 2A were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had already been published. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 18: 308­314, 2018; DOI: 10.3892/mmr.2018.9005].

MKI67 with arterial hypertension predict a poor survival for prostate cancer patients, a real-life investigation.

INTRODUCTION: Prostate cancer is a common urology malignant in males, ranking second globally. The disease is especially severe when diagnosed alongside hypertension. MKI67 is an established marker of neoplastic cell proliferation in humans, but the significance of its prognostic value in patients with prostate cancer and hypertension requires further research. METHODS: In this retrospective analysis, we evaluated 296 hypertensive prostate cancer patients between March 2, 2012, and November 1, 2015. We used Cox regression models and prediction analysis to assess overall survival. Furthermore, we created a nomogram and verified its accuracy using a calibration curve. RESULTS: Of all participants, 101 (34.12%) died. Our multi-factor analysis revealed that MKI67 expression was associated with an increased hazard ratio of death (> fivefold) (Hazard Ratio 5.829, 95% CI 3.349-10.138, p value < 0.01) and progression (twofold) (HR 2.059, 95% CI 1.368-3.102, p value < 0.01). Our Lasso analysis model displayed that several factors, including heart failure, smoking, ACS, serum albumin, Gealson score, prognostic nutritional index, MKI67 expression, surgery, and stage were high risks of prostate cancer. To ensure each covariate's contribution to cancer prognosis, we created a Cox model nomogram, which accurately predicted the risk of death (C-statistic of 0.8289) and had a proper calibration plot for risk assessment. CONCLUSION: MKI67 expression predicts poor outcomes for overall mortality in prostate cancer and hypertension patients. Additionally, our cross-validated multivariate score, which includes MKI67, demonstrated accuracy efficacy of predicting prognosis.

Case report: video-assisted thoracoscopic surgery for pulmonary arteriovenous malformation using near-infrared fluorescence with indocyanine green.

BACKGROUND: Pulmonary arteriovenous malformation (PAVM) is an abnormal communication between pulmonary vasculatures and has an unclear boundary with surrounding lung tissues. At present, surgeons can only determine its location by preoperative imaging and intraoperative palpation, despite its soft texture. Indocyanine green(ICG), a near-infrared fluorophore, has been demonstrated useful in the accurate identification of vascular tissue. Therefore, we explored its application in PAVM cases. CASE PRESENTATION: We present two PAVM cases using near-infrared fluorescence (NIF) with 25 mg ICG at 5 mg/ml to achieve intraoperative visualization of the lesion in video-assisted thoracoscopic surgery (VATS). Under the NIF mode, ICG systemic injection led to successive signaling of the anomaly and normal tissues in merely 10 s, which helped us distinguish them efficiently and precisely. A peak signal-to-background ratio of 2.2 confirmed the significant fluorescence difference and excluded interference from carbon dust. CONCLUSIONS: We are the first to report the use of such an approach in delineating the margin of vascular malformation with high contrast, and this new finding may help minimize the damage to lung function in PAVM treatment. Further exploration and validation are needed to determine its role.

Indocyanine green inhalation visualizes lung tumour during video-assisted thoracoscopic surgery.

OBJECTIVES: Accurate intraoperative identification of small lung tumours is crucial for precise resection of these lesions during video-assisted thoracoscopic surgery. This study aimed to evaluate the feasibility and safety of indocyanine green (ICG) inhalation for intraoperative visualization of lung tumours. METHODS: From January 2022 to May 2022, 43 patients with lung nodules were included into this study. All patients received intraoperative ICG inhalation for visualization of lung tumours under near-infrared imaging. The primary outcomes of this trial were the detection rate and background-tumour ratio of lung nodules, and the secondary objectives were time to search for nodules and operative time to nodules excision. RESULTS: A total of 50 pulmonary nodules in 43 patients were identified and completely resected. And 44 lung nodules were detected during intraoperative fluorescent exploration with a median inhaled ICG dose of 18.8 mg. In vivo, the median background-tumour ratio was 7.10. The median detection time of nodules was 100 s and the median operative time to nodules excision was 18 min. Quantification analysis showed that the fluorescence intensity of postoperative sputum declined to ∼10% of the first fluorescent sputum within 20 h. No adverse events attributed to ICG inhalation were recorded during the follow-up period. CONCLUSIONS: Intraoperative inhalation of ICG was a feasible and safe method for detection of lung tumours at low dose of ICG. This technique could be a remedial measure for identification of unpalpable lung nodules without preoperative localization. TRIAL REGISTRATION: Chinese Clinical Trial Registry, Identifier: ChiCTR2100053708.

Activation of assembly factor for spindle microtubules triggers progression of renal cell carcinoma via Wnt3a pathway.

Renal cell carcinoma, shorted as RCC is a well-known urological cancer with high level of morbidity and mortality. Although the regulatory role of the spindle microtubule assembly factor (ASPM) in tumor progression has been established, its relationship to the development of RCC remains unclear. To determine the significance of this gene in RCC, we examined its expression in RCC patients in the TCGA database and compared ASPM level between clinical samples of normal tissues and RCC tissues collected at our center. The prognostic relevance of ASPM was assessed by generating Kaplan-Meier survival curves and log-rank functions. Following alteration of ASPM expression using sh-ASPM or oe-ASPM transfection, RCC cell characteristics were evaluated through CCK-8, Transwell, and colony formation assays. Western blot analysis was conducted to measure levels of genes affected by ASPM, and rescue experiments were performed to explore the involvement of Wnt3a signaling in ASPM-mediated malignancy in RCC. Our findings indicate that ASPM is upregulated in RCC samples, and its levels are associated with the long-term survival of RCC patients. ASPM promotes the migration, proliferation, and invasiveness of RCC cells, and the Wnt3a pathway may be implicated in this process. In conclusion, these results indicate that ASPM contributes to the cancer progression of RCC by targeting the Wnt3a signaling pathway.

Artificial-intelligence-based computed tomography histogram analysis predicting tumor invasiveness of lung adenocarcinomas manifesting as radiological part-solid nodules.

Background: Tumor invasiveness plays a key role in determining surgical strategy and patient prognosis in clinical practice. The study aimed to explore artificial-intelligence-based computed tomography (CT) histogram indicators significantly related to the invasion status of lung adenocarcinoma appearing as part-solid nodules (PSNs), and to construct radiomics models for prediction of tumor invasiveness. Methods: We identified surgically resected lung adenocarcinomas manifesting as PSNs in Peking University People's Hospital from January 2014 to October 2019. Tumors were categorized as adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) by comprehensive pathological assessment. The whole cohort was randomly assigned into a training (70%, n=832) and a validation cohort (30%, n=356) to establish and validate the prediction model. An artificial-intelligence-based algorithm (InferRead CT Lung) was applied to extract CT histogram parameters for each pulmonary nodule. For feature selection, multivariate regression models were built to identify factors associated with tumor invasiveness. Logistic regression classifier was used for radiomics model building. The predictive performance of the model was then evaluated by ROC and calibration curves. Results: In total, 299 AIS/MIAs and 889 IACs were included. In the training cohort, multivariate logistic regression analysis demonstrated that age [odds ratio (OR), 1.020; 95% CI, 1.004-1.037; p=0.017], smoking history (OR, 1.846; 95% CI, 1.058-3.221; p=0.031), solid mean density (OR, 1.014; 95% CI, 1.004-1.024; p=0.008], solid volume (OR, 5.858; 95% CI, 1.259-27.247; p = 0.037), pleural retraction sign (OR, 3.179; 95% CI, 1.057-9.559; p = 0.039), variance (OR, 0.570; 95% CI, 0.399-0.813; p=0.002), and entropy (OR, 4.606; 95% CI, 2.750-7.717; p<0.001) were independent predictors for IAC. The areas under the curve (AUCs) in the training and validation cohorts indicated a better discriminative ability of the histogram model (AUC=0.892) compared with the clinical model (AUC=0.852) and integrated model (AUC=0.886). Conclusion: We developed an AI-based histogram model, which could reliably predict tumor invasiveness in lung adenocarcinoma manifesting as PSNs. This finding would provide promising value in guiding the precision management of PSNs in the daily practice.

Mechanism Study on Radiosensitization Effect of Curcumin in Bladder Cancer Cells Regulated by Filamin A.

Objective: To study the radiosensitization effect of curcumin, a natural product with anti-inflammatory and anti-cancer properties, in bladder cancer cells and identify the specific role of FLNA gene in that process. Methods: CCK-8 method was initially adopted to identify the proper interventional concentration of curcumin. T24 bladder cancer cells were subjected to CCK-8, flow cytometry, and colony formation assay to study the cell biological behaviors under different interventions. γ-H2AX test was performed to test the level of damage in T24 cells. RT-qPCR and Western blot were conducted to measure FLNA mRNA and protein levels. Results: Low-dose curcumin (10, 20 µM) following X-ray exposure resulted in increased DNA damage, augmented apoptosis, and reduced proliferation of T24 cells. Certain radiosensitization was demonstrated when curcumin was applied at 10 µM. Additionally, elevation of FLNA gene and protein levels was also indicated upon combination treatment. Conclusion: Low-dose curcumin has certain radiosensitization effect in bladder cancer, where FLNA plays a certain regulatory role.

Outcome of near-infrared fluorescence-navigated pulmonary metastasectomy for hepatocellular carcinoma.

OBJECTIVES: Pulmonary metastasectomy for hepatocellular carcinoma (HCC) is suitable in highly selected patients. However, complete resection is challenging in HCC patients with multiple lung metastases. We aimed to describe the clinical utility and survival outcome of indocyanine green (ICG) fluorescence-navigated resection of HCC lung metastases. METHODS: From October 2015 to March 2021, 15 HCC patients with pulmonary metastasis underwent near-infra-red (NIR) fluorescence imaging thoracoscopic surgery. ICG was administered through peripheral veins preoperatively. All suspected lesions detected by palpation, white-light thoracoscopy or NIR imaging were resected. After metastasectomy, all patients were followed up at regular intervals of 6-12 months. RESULTS: A total of 90 metastatic HCC nodules were resected in 15 patients. All patients received sublobar resections, during which 89 lesions were removed by wedge resection and 1 lesion was managed via segmentectomy. Under NIR fluorescence imaging, 81 nodules successfully demonstrated fluorescence during the surgery, while 9 metastatic nodules were undetected. The median signal-to-background ratio of the nodules was 3.34. Five patients died and 7 patients relapsed by the end of observation. The median overall survival and disease-free survival were 47.1 and 17.3 months, respectively. The 1-year overall survival and disease-free survival rates were 71.1% and 57.8%, respectively. CONCLUSIONS: ICG fluorescence imaging technology is useful for visualization of the peripheral tumours to assist in pulmonary metastasectomy for HCC. In addition, this technology has the potential to detect the small tumour that is missed in preoperative examinations, which might be beneficial for HCC patients with multiple lung metastases.

EGFR mutation is not a prognostic factor for CNS metastasis in curatively resected lung adenocarcinoma patients.

INTRODUCTION: For NSCLC patients with complete resection, the prognostic role of EGFR mutation for recurrence, especially for CNS metastasis, is still controversial. In this study, we aimed to identify the characteristics of the recurrence pattern of lung adenocarcinoma based on EGFR mutation status. METHODS: Overall, 888 patients with completely surgically resected LUAD who underwent EGFR mutation status analysis from two Chinese institutions were included. Sites and data of initial recurrence were recorded. The recurrence patterns according to EGFR mutation status were estimated by Kaplan-Meier analysis, and hazard rate curves were generated. RESULTS: 245 (27.6%) of 888 patients suffered from recurrence. Before and after PSM, there were no statistically significant differences between the EGFR mutation and EGFR WT groups for all types of recurrence, including CNS metastasis. Multivariable Cox analysis revealed that EGFR status was not a risk factor for all types of recurrence, including CNS metastasis (HR 0.88, 95% CI 0.54-1.46, p = 0.632). The CNS metastasis hazard curve in the EGFR mutation group showed that the first peak occurred at approximately 24-26 months after surgery, which was 10 months later than that in the EGFR WT group. In addition, the second peak time in the EGFR mutation group was approximately 2 years later than that in the EGFR WT group. CONCLUSIONS: EGFR mutation was not an independent prognostic factor for postoperative recurrence. EGFR-mutated LUADs did not have a clinical course with a higher incidence of CNS metastasis. However, the peak hazards for recurrence of CNS metastasis occur at a later time point in the EGFR mutant group compared with the EGFR wild type group.