Comparative Study of Indocyanine Green Fluorescence Imaging in Lung Cancer with Near-Infrared-I/II Windows.

BACKGROUND: We compare the application of intravenous indocyanine green (ICG) fluorescence imaging in lung cancer with near-infrared-I (NIR-I) and near-infrared-II (NIR-II) windows. METHODS: From March to December 2022, we enrolled patients who received an intravenous injection of ICG (5 mg/kg) 1 day before the planned lung cancer surgery. The lung cancer nodules were imaged by NIR-I/II fluorescence imaging systems, and the tumor-to-normal-tissue ratio (TNR) was calculated. In addition, the fluorescence intensity and signal-to-background ratio (SBR) of capillary glass tubes containing ICG covered with different thicknesses of lung tissue were measured by NIR-I/II fluorescence imaging systems. RESULTS: In this study, 102 patients were enrolled, and the mean age was 59.9 ± 9.2 years. A total of 96 (94.1%) and 98 (96.1%) lung nodules were successfully imaged with NIR-I and NIR-II fluorescence, and the TNR of NIR-II was significantly higher than that of NIR-I (3.9 ± 1.3 versus 2.4 ± 0.6, P < 0.001). In multiple linear regression, solid nodules (P < 0.001) and squamous cell carcinoma (P < 0.001) were independent predictors of a higher TNR of NIR-I/II. When capillary glass tubes were covered with lung tissue whose thickness was more than 2 mm, the fluorescence intensity and the SBR of NIR-II were significantly higher than those of NIR-I. CONCLUSIONS: We verified the feasibility of NIR-II fluorescence imaging in intravenous ICG lung cancer imaging for the first time. NIR-II fluorescence can improve the TNR and penetration depth of lung cancer with promising clinical prospects.

Analysis of the distribution across media, migration, and related driving factors of fluoride in cold and arid lakes during the freezing period.

Fluoride pollution in water has become a global challenge. This challenge especially affects China as a country experiencing serious fluoride pollution. While the have been past studies on the spatial distribution of fluoride, there has been less attention on different forms of fluoride. This study collected 176 samples (60, 40, and 76 ice, water, and sediment samples, respectively) from Lake Ulansuhai during the freezing period. The occurrence and spatial distribution characteristics of fluoride in lake ice-water-sediment were explored using Kriging interpolation, Piper three-line diagram, and Gibbs diagram analysis methods. The migration and transformation of fluoride during the freezing period were revealed and the factors influencing fluoride concentration in the water body were discussed considering the hydrochemical characteristics of lake surface water. The results showed that the average fluoride concentrations in the upper ice, middle ice and lower ice were 0.18, 0.09, and 0.12 mg/L, respectively, decreasing from north to south in the lake. The average concentrations of fluoride in surface water and bottom water were 0.63 and 0.83 mg/L, respectively. The concentrations of fluoride in ice and water were within the World Health Organisation drinking water threshold of 1.50 mg/L and the Class III Chinese surface water standard (GB3838-2002). The average sediment total fluorine was 1344.38 ± 200 mg/kg, significantly exceeding the global average (321 mg/kg) and decreasing with depth. The contents of water soluble, exchangeable, Fe/Mn bound, organic bound, and residual fluorides were 40.22-47.18, 13.24-43.23, 49.52-160.48, and 71.59-173.03 mg/kg, respectively. There was a significant positive correlation between fluoride concentration in ice and that in water. The change in fluoride concentration in water was mainly due to specific climatic and geographical conditions, pH, hydrochemical characteristics and ice sealing. This study is of great significance for the management of high-fluorine lakes in arid and semi-arid areas.

New and effective EGFR-targeted fluorescence imaging technology for intraoperative rapid determination of lung cancer in freshly isolated tissue.

PURPOSE: During lung cancer surgery, it is very important to define tumor boundaries and determine the surgical margin distance. In previous research, systemically application of fluorescent probes can help medical professionals determine the boundaries of tumors and find small tumors and metastases, thereby improving the accuracy of surgical resection. However, there are very few safe and effective probes that can be applied to clinical trials up to now, which limits the clinical application of fluorescence imaging. Here we developed a new technology that can quickly identify the tumor area in the resected lung tissue during the operation and distinguish the tumor boundary and metastatic lymph nodes. EXPERIMENTAL DESIGN: For animal studies, a PDX model of lung cancer was established. The tumors, lungs, and peritumoral muscle tissues of tumor-bearing mice were surgically removed and incubated with a probe targeting epidermal growth factor receptor (EGFR) for 20 min, and then imaged by a closed-field near-infrared two-zone (NIR-II) fluorescence imaging system. For clinical samples, ten surgically removed lung tissues and 60 lymph nodes from 10 lung cancer patients undergoing radical resection were incubated with the targeting probe immediately after intraoperative resection and imaged to identify the tumor area and distinguish the tumor boundary and metastatic lymph nodes. The accuracy of fluorescence imaging was confirmed by HE staining and immunohistochemistry. RESULTS: The ex vivo animal imaging experiments showed a fluorescence enhancement of tumor tissue. For clinical samples, our results showed that this new technology yielded more than 85.7% sensitivity and 100% specificity in identifying the tumor area in the resected lung tissue. The average fluorescence tumor-to-background ratio was 2.5 ± 1.3. Furthermore, we also used this technique to image metastatic lymph nodes intraoperatively and showed that metastatic lymph nodes have brighter fluorescence than normal lymph nodes, as the average fluorescence tumor-to-background signal ratio was 2.7 ± 1.1. Calculations on the results of the fluorescence signal in relation to the number of metastatic lymph nodes yielded values of 77.8% for sensitivity and 92.1% for specificity. We expect this new technology to be a useful diagnostic tool for rapid intraoperative pathological detection and margin determination. CONCLUSIONS: By using fluorescently labeled anti-human EGFR recombinant antibody scFv fragment to incubate freshly isolated tissues during surgery, the probes can quickly accumulate in lung cancer tissues, which can be used to quickly identify tumor areas in the resected lung tissues and distinguish tumor boundaries and find metastases in lymph nodes. This technology is expected to be used for rapid intraoperative pathological detection and margin determination.

Genomic characterisation of pulmonary subsolid nodules: mutational landscape and radiological features.

BACKGROUND: Lung adenocarcinomas (LUADs) that display radiologically as subsolid nodules (SSNs) exhibit more indolent biological behaviour than solid LUADs. SSNs, commonly encompassing pre-invasive and invasive yet early-stage adenocarcinomas, can be categorised as pure ground-glass nodules and part-solid nodules. The genomic characteristics of SSNs remain poorly understood. METHODS: We subjected 154 SSN samples from 120 treatment-naïve Chinese patients to whole-exome sequencing. Clinical parameters and radiological features of these SSNs were collected. The genomic landscape of SSNs and differences from that of advanced-stage LUADs were defined. In addition, we investigated the intratumour heterogeneity and clonal relationship of multifocal SSNs and conducted radiogenomic analysis to link imaging and molecular characteristics of SSNs. Fisher's exact and Wilcoxon rank sum tests were used in the statistical analysis. RESULTS: The median somatic mutation rate across the SSN cohort was 1.12 mutations per Mb. Mutations in EGFR were the most prominent and significant variation, followed by those in RBM10, TP53, STK11 and KRAS. The differences between SSNs and advanced-stage LUADs at a genomic level were unravelled. Branched evolution and remarkable genomic heterogeneity were demonstrated in SSNs. Although multicentric origin was predominant, we also detected early metastatic events among multifocal SSNs. Using radiogenomic analysis, we found that higher ratios of solid components in SSNs were accompanied by significantly higher mutation frequencies in EGFR, TP53, RBM10 and ARID1B, suggesting that these genes play roles in the progression of LUADs. CONCLUSIONS: Our study provides the first comprehensive description of the mutational landscape and radiogenomic mapping of SSNs.

Risk assessment and source apportionment of available atmospheric heavy metal in a typical sandy area reservoir in Inner Mongolia, China.

This study evaluated dry and wet deposition of atmospheric heavy metals (HMs) in a sandy area of Inner Mongolia, China, with the Dahekou Reservoir, Xilin Gol League, adopted as the study area. Monthly monitoring of atmospheric HM dry and wet deposition was conducted over one year (2021 to 2022) at 12 monitoring points, producing 144 dry and wet deposition samples, respectively. The sample contents of eight HMs (Cr, Ni, Pb, Cu, Zn, Mn, As, and Cd) were determined to estimate the fluxes of available forms of heavy metal (AHM) in dry and wet deposition. The potential ecological index (Eri), risk assessment coding (RAC), and ratio of secondary phase to primary phase (RSP) were used to evaluate the impact of atmospheric HM dry deposition on ecological security. Correlation analysis, principal component analysis, and the absolute principal component scores-multiple linear regression (APCS-MLR) receptor model were used to quantitatively analyze the sources of AHMs in atmospheric dry and wet deposition. The results showed that the study area experienced annual dry and wet deposition fluxes of AHMs of 1712.59 kg and 534.97 kg, respectively. Atmospheric heavy metal dry deposition over the entire year presented a strong ecological risk, with Cd contributing most to this risk. Risk assessment of HM speciation showed that the greatest risks of migration and transformation were for Cd and Pb. The APCS-MLR receptor model identified five and three sources of dry and wet deposition, respectively, in order of proportion of total contribution of: natural wind and sand > road traffic and coal combustion > mineral mining > other human activities > industrial soot.

[Whole Process Analysis and Fate Behavior of Microplastics in Urban Wastewater Treatment Plants, Including their Occurrence Forms, Components, and Removal Efficiency].

Microplastics are among the most difficult new pollutants to remove in wastewater treatment plants. In order to explore the occurrence form, size distribution, composition, removal efficiency, migration law, and fate behavior characteristics of microplastic particles in sewage plants, taking a sewage treatment plant in Hohhot as an example, a total of 17 sampling sites were set up. The LAS X software counted the shape, abundance, and size of microplastics and conducted a full-process analysis. The results showed that： fibrous microplastics had the highest abundance and widest distribution and were the main form of existence, accounting for 61.8% of the total abundance； the size of microplastics ranged mainly between 0 and 1.00 mm, and among the four sizes, the abundance of microplastics 0.25 to 0.50 mm in China was the highest, accounting for 32.9%. Among the eight types of plastic components detected, polyester substances （PET, PBT）, cellulose, and polypropylene （PP） were the main components, accounting for 25%, 21%, and 17%, respectively. The influent abundance of the sewage plant was （73 ±5） n·L-1, the effluent abundance was （14 ±2） n·L-1, and the overall removal rate was （80.8 ±12.1）%. Among the three treatment stages of the sewage plant, only the primary treatment played a role in removal, and the abundance of microplastics surged in the secondary treatment. Different structures playing a major role in the removal of microplastics were fine grids （49.2 ±7.4）% and secondary sedimentation tanks （92.4 ±13.9）%. Microplastics mainly existed in the form of fibers, fragments, and films. The proportion of fibers was approximately 70%, and the size of fragments was mainly concentrated between 0.50 and 5.00 mm. Most fragments were in the range of 5.00 mm, accounting for 50%, making them the main form apart from fibrous. The film-like size was mostly concentrated in the range of less than 0.50 mm, accounting for more than 10%. Therefore, improving the removal of small-sized fibrous and film-like microplastics and large-sized fragmented microplastic particles can effectively reduce the pollution risk of microplastics in the environment caused by sewage plant drainage.

Intestinal microbiota regulates colonic inflammation in fluorosis mice by TLR/NF-κB pathway through short-chain fatty acids.

Intestinal inflammation and microbial dysbiosis are found simultaneously in patients with fluorosis. However, whether the inflammation derived from fluoride exposure only or intestinal microbial disorders has not been clarified. In this study, 100 mg/L NaF exposure for 90 days significantly elevated the expressions of inflammatory factors (TNF-α, IL-1ß, IL-6, IFN-γ, TGF-ß, and IL-10), and the levels of TLR4, TRAF6, Myd88, IKKß, and NF-κB P65 in mouse colon, while the above factors were reduced in pseudo germ-free mice with fluorosis, hinting that disordered microbiota might play a more direct role in the development of colonic inflammation than fluoride. Fecal microbiota transplantation (FMT) lowered the levels of inflammatory factors and inactivated the TLR/NF-κB pathway in fluoride-exposed mice. In addition, supplementing short-chain fatty acids (SCFAs) exhibited the identical effects to the model of FMT. In summary, intestinal microbiota may alleviate the colonic inflammatory of mice with fluorosis by regulating TLR/NF-κB pathway through SCFAs.

The mechanism investigation of mutation genes in liver and lung metastasis of colorectal cancer by using NGS technique.

BACKGROUND: We analyzed the somatic mutation distributions as well as pathways associated with liver/lung metastasis of CRC using next-generation sequencing panel. METHODS: We detected the somatic SNV/indel mutations of 1126 tumor-related genes in CRC, liver/lung metastasis of CRC and liver /lung cancer. We combined the MSK and GEO datasets to identified the genes and pathways related to the metastasis of CRC. RESULTS: We identified 174 genes related to liver metastasis of CRC, 78 genes related to lung metastasis of CRC, and 57 genes related to both liver and lung metastasis in two datasets. The genes related to liver and lung metastasis were collectively enriched in various pathways. Finally we found that IRS1, BRCA2, EphA5, PTPRD, BRAF, and PTEN could be prognosis-related genes in CRC metastasis. CONCLUSION: Our finding may help clarify the pathogenesis of CRC metastasis more clearly and provide new perspectives for the diagnosis and treatment of CRC metastasis.

Lung Cancer in a Patient With Pulmonary Artery Sling: A Case Report.

Introduction: Pulmonary artery sling (PAS) is a rare congenital vascular anomaly that results when the left pulmonary artery arises from the right pulmonary artery. There is little relevant literature on lobectomy for the treatment of lung cancer in patients with PAS, and the prognosis is unknown. Case Description: A 54-year-old asymptomatic man was found to have a nodule on the left lower lobe of the lung, which measured 2.5 cm. The patient also had PAS. Three-dimensional computed tomography angiography confirmed that the left pulmonary artery arose from the right pulmonary artery and passed between the main trachea and the esophagus toward the left thorax. No obvious contraindication was found in the preoperative examination, and the patient successfully underwent lobectomy of the left lower lobe by video-assisted thoracoscopic surgery. Histological examination of the lesion revealed invasive adenocarcinoma. The postoperative course was uneventful, and no complications occurred in the subsequent 3 years of follow-up. Conclusions: Lobectomy in a lung cancer patient with PAS did not increase perioperative risk and had no significant effect on prognosis.

Case Report: The Second Near-Infrared Window Indocyanine Green Angiography in Giant Mediastinal Tumor Resection.

Giant mediastinal tumors are often accompanied by the abundant blood supply and have an unclear border with adjacent vessels, making surgical resection difficult. Failure to distinguish the complex vessels during the operation often results in vascular injury or hemorrhage, which severely increases the operation time and perioperative risk. At present, surgeons can only determine the vessel's location and course by preoperative imaging and intraoperative exploration in visible light. Therefore, we report a case of a giant anterosuperior mediastinal tumor resection assisted by near-infrared (NIR) indocyanine green (ICG) angiography. Furthermore, we applied the second near-infrared window (NIR-II, 1,000-1,700 nm) to detect the fluorescence signals in the clinic for the first time. The NIR-II window is able to explore deeper tissues in centimeters and obtain higher resolution in millimeters than the traditional first near-infrared window (NIR-I, 700-900 nm). Finally, NIR-II ICG angiography shows the clear location and course of the vessels, which can help surgeons reduce unnecessary blood vessel injury and increase the safety of mediastinal tumor resection.

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.

Somatic gene mutation signatures predict cancer type and prognosis in multiple cancers with pan-cancer 1000 gene panel.

Most cancers are caused by somatic mutations. Some common mutations in the same cancer type can form a "signature" to specifically predict the prognosis or to distinguish it from other cancers. In this study, 710 somatic cell mutations were identified in 142 cases, including digestive, lung and urogenital cancers, and the digestive cancers were further divided into liver, stomach, intestinal, esophageal and cardia cancer. The above mutations were located in 166 genes. In addition, a group of high-frequency mutation genes with specific characteristics were screened to form predictive signatures for each cancer. Verification using TCGA suggested that the signatures could predict the stages, progression-free survival, and overall survival of digestive, intestinal, and liver cancers (P < 0.05). The validation cases further confirmed the predictive role of digestive and liver cancers signatures in diagnosis and prognosis. Overall, this study established predictive signatures for different cancer systems and their subtypes. These findings enable a better understanding in cancer genome, and contribute to the personalized diagnosis and treatment.

[Clinical Characteristics and Prognosis of Sub-centimeter Lung Adenocarcinoma].

BACKGROUND: With the increase of lung cancer screening, more and more patients have been diagnosed as sub-centimeter (≤1 cm) lung adenocarcinoma. Sub-centimeter lung adenocarcinoma is mostly early stage lung cancer, but the research on sub-centimeter lung adenocarcinoma is still insufficient. This study analyzed the clinical characteristics and prognosis of patients with sub-centimeter lung adenocarcinoma in order to provide the basis for the diagnosis and treatment of such patients. METHODS: A retrospective study was performed to analyze patients with sub-centimeter lung adenocarcinoma who underwent VATS in Peking University People's Hospital from January 2012 to December 2016. Patients were divided into pure ground-glass nodules (pGGN) group, mixed ground-glass nodules (mGGN) group and solid nodules (SN) group according to the features of nodular imaging. The clinical characteristics of the three groups were compared and the subgroup analysis of nodules in different diameter was performed. We also performed multivariate logistic regression analyses to identify the risk factors for sub-centimeter lung invasive adenocarcinoma. RESULTS: The study included 182 patients (57 men and 125 women) with a median age of 54 (27-75) years. Female sub-centimeter lung adenocarcinoma patients had a significantly lower proportion of non-smoking history than males (P<0.001). All patients with 1 mm-10 mm pGGN, 1 mm-5 mm mGGN and 1 mm-5 mm SN had no other pathologically positive findings except for the primary lesion. Of the 46 patients with 6 mm-10 mm mGGN, 3 had pleural invasion and 1 had vascular tumor thrombus. Of the 39 patients with 6 mm-10 mm SN, 5 had pleural invasion, 2 had vascular tumor thrombus and 2 had lymph node metastasis. The pathological type in each patient with pleural invasion, vascular tumor thrombus or lymph node metastasis was invasive adenocarcinoma. Logistic regression analysis indicated that smoking history (OR=4.727, P=0.009), previous tumor history (OR=3.408, P=0.015), mGGN (OR=3.735, P=0.004), SN (OR=8.921, P<0.001) and tumor diameter >5 mm (OR=4.241, P=0.001) were independent risk factors for sub-centimeter lung invasive adenocarcinoma. The median follow-up time was 44 (22-82) months. The 5-year recurrence-free survival rate was 100.0% and the overall survival rate was 98.9%. CONCLUSIONS: Patients with sub-centimeter lung adenocarcinoma have a relatively earlier onset age. Sub-centimeter lung invasive adenocarcinoma patients with 6 mm-10 mm mGGN and 6 mm-10 mm SN may be involved in pleural invasion or lymph node metastasis. Smoking history, previous tumor history, mGGN, SN and tumor diameter >5 mm are independent risk factors for sub-centimeter lung invasive adenocarcinoma. For patients with sub-centimeter lung adenocarcinoma, early detection and appropriate surgical intervention can lead to a good prognosis.