Exploration of lymph node recurrence patterns and delineation guidelines of radiation field in middle thoracic oesophageal carcinomas after radical surgery: a real-world study.

BACKGROUND: Oesophageal squamous cell carcinoma is one of the most commonly diagnosed carcinomas in China, and postoperative radiotherapy plays an important role in improving the prognosis of patients. Carcinomas in different locations of the oesophagus could have different patterns of lymph node metastasis after surgery. METHODS: In this multicentric retrospective study, we enrolled patients with middle thoracic oesophageal squamous cell carcinomas from 3 cancer centres, and none of the patients underwent radiotherapy before or after surgery. We analysed the lymph node recurrence rates in different stations to explore the postoperative lymphatic recurrence pattern. RESULTS: From January 1st, 2014, to December 31st, 2019, 132 patients met the criteria, and were included in this study. The lymphatic recurrence rate was 62.1%. Pathological stage (P = 0.032) and lymphadenectomy method (P = 0.006) were significant predictive factors of lymph node recurrence. The recurrence rates in the supraclavicular, upper and lower paratracheal stations of lymph nodes were 32.6%, 28.8% and 16.7%, respectively, showing a high incidence. The recurrence rate of the subcarinal node station was 9.8%, while 8.3% (upper, middle and lower) thoracic para-oesophageal nodes had recurrences. CONCLUSIONS: We recommend including the supraclavicular, upper and lower paratracheal stations of lymph nodes in the postoperative radiation field in middle thoracic oesophageal carcinomas. Subcarinal station is also potentially high-risk, while whether to include thoracic para-oesophageal or abdominal nodes needs careful consideration.

Comparative study of encapsulated cannabidiol ternary solid dispersions prepared by different techniques: The application of a novel technique jet milling.

Jet milling is a common technique in ultrafine powder preparation field. It has never been used to design delivery systems. Cannabidiol (CBD) is an important cannabinoid of hemp but poor aqueous solubility limited its applications. In this study, solid dispersion (SD) technique was combined with cyclodextrin complexation technique, and jet milling was used for the first time to prepare SDs for improving CBD solubility. Different characterizations demonstrated that the dispersion effect and complexation structure of CBD SD3 prepared by jet milling were comparable to that of CBD SD2 prepared by spray drying (a common solution-based method), and were better than that of CBD SD1 prepared by cogrinding. The water solubility of CBD was increased to 20.902 µg/mL (909-fold) in CBD SD3. Besides, the antioxidant activity and cytotoxicity to tumor cells of CBD were enhanced by dispersion. This work indicated that jet milling, as a new technique with low cost and excellent applicability, could be further developed for the delivery of food functional factors or bioactive molecules.

Ulex Europaeus Agglutinin-I-Based Magnetic Isolation for the Efficient and Specific Capture of SW480 Circulating Colorectal Tumor Cells.

The efficient and specific capture of circulating tumor cells (CTCs) from patients' peripheral blood is of significant value in precise cancer diagnosis and cancer therapy. As fine targeting molecules, lectins can recognize cancer cells specifically due to the abnormal glycosylation of molecules on the cancer cell membrane and the specific binding of lectin with glycoconjugates. Herein, a Ulex europaeus agglutinin-I (UEA-I)-based magnetic isolation strategy was developed to efficiently and specifically capture α-1,2-fucose overexpression CTCs from colorectal cancer (CRC) patients' peripheral blood. Using UEA-I-modified Fe3O4 magnetic beads (termed MB-UEA-I), up to 94 and 89% of target cells (i.e., SW480 CRC cells) were captured from the cell spiking complete cell culture medium and whole blood, respectively. More than 90% of captured cells show good viability and proliferation ability without detaching from MB-UEA-I. In combination with three-color immunocytochemistry (ICC) identification, MB-UEA-I has been successfully used to capture CTCs from CRC patients' peripheral blood. The experimental results indicate a correlation between CTC characterization and tumor metastasis. Specifically, MB-UEA-I can be applied to screen early CRC by capturing CTCs when served as a liquid biopsy. The presented work offers a new insight into developing cost-effective lectin-functionalized methods for biomedical applications.

Postoperative lymphatic recurrence distribution and delineation of the radiation field in lower thoracic squamous cell esophageal carcinomas: a real-world study.

BACKGROUND: To study lymphatic recurrence distribution after radical surgery in the real world and guide clinical tumor volume delineation for regional lymph nodes during postoperative radiotherapy for lower thoracic squamous cell esophageal carcinomas. METHODS: We enrolled patients who underwent radical esophagectomy, without radiation before or after surgery, at 3 cancer hospitals. Patients were classified into groups according to tumor locations. We included patients with tumors in the lower thoracic segment and analyzed the postoperative lymph node recurrence mode. A cutoff value of 10% was used to differentiate high-risk lymph node drainage areas from others. RESULTS: We enrolled 1905 patients in the whole study series, including 652 thoracic esophageal carcinomas that met our inclusion criteria; there were 241 cases of lower thoracic esophageal carcinomas. 1st, 2nd, 4th, 7th, 8th groups of lymph nodes, according to the 8th edition of the AJCC classification, displayed as high-risk recurrence areas, representing 17.8%, 23.9%, 11.7%, 10.9% and 12.2% of lymph node recurrence. Stage III-IV tumors located in the lower segment of the thoracic esophagus showed a tendency to recur in the left gastric nodes (7.9%) and celiac nodes (10.6%). CONCLUSIONS: According to our results, we recommended including the 4th, 7th and 8th groups of lymph nodes in the radiation field, and for patients with stage III-IV disease, the 17th and 20th groups of nodes should be irradiated during postoperative treatment. Whether including 1st/2nd groups in preventive irradiation needed more proofs.

Research progress on intervention effect and mechanism of protocatechuic acid on nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) has become a surge burden worldwide due to its high prevalence, with complicated deterioration symptoms such as liver fibrosis and cancer. No effective drugs are available for NALFD so far. The rapid growth of clinical demand has prompted the treatment of NAFLD to become a research hotspot. Protocatechuic acid (PCA) is a natural secondary metabolite commonly found in fruits, vegetables, grains, and herbal medicine. It is also the major internal metabolites of anthocyanins and other polyphenols. In the present manuscript, food sources, metabolic absorption, and efficacy of PCA were summarized while analyzing its role in improving NAFLD, as well as the mechanism involved. The results indicated that PCA could ameliorate NAFLD by regulating glucose and lipid metabolism, oxidative stress and inflammation, gut microbiota and metabolites. It was proposed for the first time that PCA might reduce NAFLD by enhancing the energy consumption of brown adipose tissue (BAT). However, the PCA administration mode and dose for NAFLD remain inconclusive. Fresh insights into the specific molecular mechanisms are required, while clinical trials are essential in the future. This review provides new targets and reasoning for the clinical application of PCA in the prevention and treatment of NAFLD.

One-pot synthesis of Ln3+-doped porous BiF3@PAA nanospheres for temperature sensing and pH-responsive drug delivery guided by CT imaging.

The design and synthesis of responsive inorganic nanocapsules have attracted intensive research interest in cancer treatment. The combination of non-invasive diagnosis and chemotherapy into a single theranostic nanoplatform is prospective in the biomedical field. In this work, a polyacrylic acid (PAA)-functionalized porous BiF3:Yb,Er nanocarrier was constructed via a straightforward one-pot solvothermal strategy. Compared with the undoped BiF3 sub-microspheres, the lanthanide ion (Ln3+) doping endowed the BiF3 material with a smaller size and increased BET specific surface area and pore volume, which make it suitable as a drug carrier. It was found that the synthesized nanomaterial could effectively relieve the side effects of doxorubicin (DOX) and exhibited pH-dependent DOX loading and release. Its satisfactory biocompatibility and efficient tumor inhibition were emphasized by a series of in vitro/in vivo experiments. In addition, the synthesized nanomaterial exhibited favorable CT contrast efficacy due to the excellent X-ray attenuation coefficient of Bi. Moreover, characteristic upconversion luminescence and temperature sensing in a wide temperature range were realized over the synthesized BiF3:Yb,Er sample. Therefore, carboxyl-functionalized BiF3:Yb,Er can be expected to be an ideal candidate in the fabrication of temperature sensing and multifunctional theranostic nanoplatforms.

UCNP-Bi2 Se3 Upconverting Nanohybrid for Upconversion Luminescence and CT Imaging and Photothermal Therapy.

Non-invasive theranostics that integrate the advantages of multimodality imaging and therapeutics have great potential in the field of biomedicine. Herein, a new nanohybrid based on Bi2 Se3 -conjugated upconversion nanoparticles (UCNPs) has been successfully developed through a simple in situ growth strategy. Under 808 nm near-infrared laser irradiation, the UCNPs can emit bright visible light, whereas the Bi2 Se3 nanomaterial exhibits efficient photothermal conversion capacity. Moreover, the as-synthesized UCNP-Bi2 Se3 nanohybrid exhibits efficient cell upconversion luminescence (UCL), reasonable CT imaging, and admirable cancer cell ablation capacity, further emphasizing the efficiency of this strategy for simultaneous UCL imaging and photothermal therapy. The designed theranostic strategy guided by dual-modal imaging endowed with real-time dynamic monitoring, remote controllability, and non-invasiveness makes the UCNP-Bi2 Se3 nanohybrid an ideal candidate for non-invasive multimodal imaging-guided photothermal therapy for the precise diagnosis and treatment of cancer.

Risk Stratification Of Diffuse Large B-Cell Lymphoma With Interim PET/CT By Combining Deauville Scores And International Prognostic Index.

PURPOSE: Prognostic evaluation using interim positron emission tomography/computed tomography (interim PET/CT; I-PET) remains controversial. For any predictor, the prognosis of patients around its cutoff value is most uncertain. If the patients around the cutoff value could be subdivided by another factor, like the international prognostic index (IPI), it may improve the predictive power of I-PET. The combination of I-PET and IPI for risk stratification of patients was explored in this study. PATIENTS AND METHODS: One hundred and eleven diffuse large B-cell lymphoma (DLBCL) patients treated with R-CHOP therapy were included retrospectively, 59 of whom underwent PET/CT after three or four cycles of treatment (I-PET). Fifty-two patients underwent PET/CT after five or six cycles of treatment (end of treatment; E-PET). RESULTS: When Deauville 5-point scale (5-DS) scores of 4-5 were classified as a positive scan (denoted by DS [score 4]), there was no significant difference in progression-free survival (PFS) between I-PET positive and negative patients (P=0.151). Further, patients with 5-DS score 3 and high IPI were stratified into I-PET positive-, whereas those with 5-DS score 3 and low IPI were classified into I-PET negative scan groups. Under this stratification, there was a significant difference in PFS between I-PET positive and negative patients (P=0.001). The sensitivity, positive predictive value, and negative predictive value for 2-year PFS for the combination score were higher than DS (score 4) alone (66.7% vs 33.3%, 50.0%vs 37.5%, 93.6% vs 88.2%) whereas specificity was almost the same (90.0% vs 88.0%). CONCLUSION: Subdivision of patients with 5-DS score 3 by IPI improved prognostic prediction accuracy. The IPI adds strength to 5-DS in I-PET to detect patients with good or poor prognosis. Compared with other combinations of I-PET and IPI, dividing the patients around the cutoff value of 5-DS by IPI was easily accepted by clinicians and allowed them to decide on further treatment practically.

Construction of lanthanide-doped upconversion nanoparticle-Uelx Europaeus Agglutinin-I bioconjugates with brightness red emission for ultrasensitive in vivo imaging of colorectal tumor.

Lanthanide-doped upconversion nanoparticles (UCNPs)-based active targeting optical bioimaging has attracted tremendous scientific interest because of its noninvasive real-time signal feedback, superior tissue penetration depth and high spatial resolution in early diagnosis of disease. Herein, we synthesize a novel carboxy-terminated silica coated NaErF4: 10% Yb@NaYF4: 40% Yb@NaNdF4: 10% Yb@NaGdF4: 20% Yb UCNPs (termed as UCNP@SiO2-COOH) with 808 nm near-infrared (NIR) excitation and bright 655 nm upconversion luminescence (UCL) emission for realizing deep tissue imaging. Under 808 nm NIR laser excitation (1.5 W cm-2), the UCL of UCNP@SiO2-COOH with relative low concentration (2 mg mL-1) can be successfully visualized under a chicken breast slice with 10 mm thickness. After conjugated with various molecules including NH2-PEG3400-COOH, peptide D-SP5 and Uelx Europaeus Agglutinin-I (UEA-I), biodistributions, clearance pathways and tumor-targeting capacities of the UCNP@SiO2-COOH and corresponding bioconjugates (termed as UCNP@SiO2-PEG, UCNP@SiO2-D-SP5 and UCNP@SiO2-UEA-I, respectively) were investigated by tracking the UCL intensities of livers, kidneys and tumors. Both of in vitro and in vivo experimental results reveal that there is no significant difference for their in vivo biodistributions and clearance pathways. The UCNP@SiO2-UEA-I exhibits much higher SW480 tumor-targeting capacity than those of other bioconjugates. In particular, the as-prepared UCNP@SiO2-UEA-I even to visualize ultrasmall (c.a. 3 mm3 in volume) subcutaneous SW480 tumor in Balb/c nude mouse through intravenous administration. The study implies that the red UCL emitted UCNPs with a minimized heating effect is suitable for deep tissue biomedical imaging and UCNP@SiO2-UEA-I can serve as an efficient optical probe for early diagnosis of SW480 tumor.

Designing of UCNPs@Bi@SiO2 Hybrid Theranostic Nanoplatforms for Simultaneous Multimodal Imaging and Photothermal Therapy.

Herein, a novel multifunctional nanoplatform was designed toward multimodality imaging and photothermal therapy (PTT). It was found that Bi nanoparticles could grow in situ on the surface of NaYF4:20%Yb,2%Er@NaYF4:40%Yb@NaGdF4 core-shell nanoparticles (labeled as UCNPs). In this structure, UCNPs were mainly employed as an upconversion luminescence (UCL) imaging agent, whereas the Bi nanoparticles worked as an effective CT imaging and photothermal agent. Importantly, a dense SiO2 shell was employed to protect the Bi nanoparticles from oxidation, and it also endowed the nanoplatform with excellent hydrophilic ability. The effective UCL/CT imaging and PTT performances were emphasized by a series of in vivo experiments, which suggest that the integrated nanoplatform with imaging and therapy functions shows great promise in the biomedical field.

Uncovering the Binding Specificities of Lectins with Cells for Precision Colorectal Cancer Diagnosis Based on Multimodal Imaging.

There is a high desire for novel targets/biomarkers to diagnose and treat colorectal cancer (CRC). Here, an approach starting from a polyacrylamide hydrogel-based lectin microarray is presented to screen the high expression of glycans on the CRC cell surface and to identify new lectin biomarkers for CRC. Three common CRC cell lines (SW480, SW620, and HCT116) and one normal colon cell line (NCM460) are profiled on the microarray with 27 lectins. The experimental results reveal that CRC cells highly express the glycans with d-galactose, d-glucose, and/or sialic acid residues, and Uelx Europaeus Agglutinin-I (UEA-I) exhibits reasonable specificity with SW480 cells. After conjugation of UEA-I with silica-coated NaGdF4:Yb3+, Er3+@NaGdF4 upconversion nanoparticles, the follow-up in vitro and in vivo experiments provide further evidence on that UEA-I can serve as tumor-targeting molecule to diagnose SW480 tumor by multimodal imaging including upconversion luminescence imaging, T1-weighted magnetic resonance imaging, and X-ray computed tomography imaging.

Polyamidoamine starburst dendrimer-activated chromatography paper-based assay for sensitive detection of telomerase activity.

Telomerase is extensively expressed in various cancer cells and recognized as a target for cancer drug discovery. In the present study, a simple and amplification-free fluorescence assay based on polyamidoamine starburst dendrimer (PAMAM dendrimer)-activated paper device is proposed for sensitive detection of telomerase activity through hybridization of Cy5 modified single strand DNA probes with telomerase extension products. The paper substrate is fabricated by hand drawing according to a template, which is low cost, instrument free and easy operation. PAMAM is rich in amino groups on its surface and employed to immobilize the telomerase substrate (TS) primer. Highly sensitive detection of telomerase activity in HeLa cell lysate of 10 cells is achieved since the PAMAM dendrimer-activated paper surface can provide high density of binding sites for immobilization of TS primer. The experimental results also demonstrate that the assay can be employed to evaluate telomerase activity levels of various cell lines and screen telomerase inhibitors.

Combined Effects of Elevated O3 Concentrations and Enhanced UV-B Radiation of the Biometric and Biochemical Properties of Soybean Roots.

Enhanced ultraviolet-B (UV-B) radiation and elevated tropospheric ozone alone may inhibit the growth of agricultural crops. However, research regarding their combined effects on growth and biochemical properties of roots is still scarce. Using open top chambers, we monitored the response of growth, secondary metabolites, endogenous hormones and enzyme activities of soybean roots to elevated O3 and enhanced UV-B individually and in combination at stages of branching, flowering and podding. Our results indicated that the root biomass decreased by 23.6, 25.2, and 27.7%, and root oxidative capacity declined by11.2, 39.9, and 55.7% exposed to elevated O3, enhanced UV-B, and O3 + UV-B, respectively, compared to the control treatment. Concentrations of quercetin and ABA were significantly increased, while concentrations of total polyphenol and P-coumaric acid responded insignificantly to elevated O3, enhanced UV-B, and O3 + UV-B during the whole period of soybean growth. Elevated O3, enhanced UV-B and O3 + UV-B showed significant negative effects on superoxide dismutase (EC 1.15.1.1) activity at flowering stage, on activities of peroxidase (EC 1.11.1.7) and catalase (EC 1.11.1.6) at podding stage, on ascorbate peroxidase activity during the whole period of soybean growth. Moreover, compared to hormones and enzyme activity, secondary metabolisms showed stronger correlation with root growth exposed to elevated O3 and enhanced UV-B individually and in combination. Our study concluded that combined effects of O3 and UV-B radiation significantly exacerbated the decline of soybean root growth, and for annual legumes, the inhibited root growth exposed to O3 and/or UV-B radiation was mostly associated with secondary metabolisms (especially flavonoids).

Combined effects of O3 and UV radiation on secondary metabolites and endogenous hormones of soybean leaves.

Enhanced ultraviolet radiation (UV) and elevated tropospheric ozone (O3) may individually cause reductions in the growth and productivity of important agricultural crops. However, research regarding their combined effects on important agricultural crops is still scarce, especially on changes in secondary metabolites and endogenous hormones, which are important protective substances and signal components that control plant responses to environment stresses. In this study, using an experimental setup of open top chambers, we monitored the responses of seed yield per plant, leaf secondary metabolites and leaf endogenous hormones under the stress of elevated O3 and enhanced UV radiation individually, as well as their combined stress. The results indicated that elevated O3 (110 ± 10 nmol mol-1 for 8 hours per day) and enhanced UV radiation (1.73 kJ h-1 m-2) significantly decreased seed yield per plant. Concentrations of rutin, queretin and total flavonoids were significantly increased under the elevated O3 treatment or the enhanced UV radiation treatment or the combination treatment at flowering and podding stages, and concentrations of rutin, queretin and total flavonoids showed significant correlations with seed yield per plant. Concentrations of ABA and IAA decreased under the three treatments. There was a significant positive correlation between the ABA concentration and seed yield and a negative correlation between the IAA concentration and seed yield. We concluded that the combined stress of elevated O3 and UV radiation significantly decreased seed yield per plant. Yield reduction was associated with changes in the concentrations of flavonoids, ABA and IAA in soybean leaves. The effects of the combined O3 and UV stress were always greater than those of the individual stresses alone.

The role of ¹8F-FDG uptake features in the differential diagnosis of solitary pulmonary lesions with PET/CT.

BACKGROUND: The aim of this study is to evaluate the value of (18)F-FDG uptake features in the diagnosis of solitary pulmonary lesions. METHODS: One hundred thirty-nine patients with solitary pulmonary lesions were divided into full uptake, circular uptake, multi-focus uptake, mild uptake, and no-uptake groups according to the uptake features of (18)F-FDG in solitary pulmonary lesions. The incidence of benign and malignant lesions and the false-positive and false-negative rates in each group were analyzed. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the method using (18)F-FDG uptake features combined with maximum standard uptake value (SUVmax) (SUV method) in the differential diagnosis of solitary pulmonary lesions were evaluated. RESULTS: There were 89 malignant and 50 benign lesions. (1) The malignant incidence of the full uptake group was 84.0% (63/75), and there were significant differences when compared with the other groups except the circular uptake group (16/23) (all P = 0.0001). The benign incidence of the multi-focus and no-uptake groups was 83.3% (10/12) and 82.4% (14/17), respectively, and there were significant differences when compared with the full uptake and the circular uptake groups, respectively (all P < 0.05). The benign incidence of the mild uptake group was 58.3% (7/12), and there were no significant differences when compared with the others except the full uptake group (all P > 0.05). No statistical significance was found between either two of the no-uptake, mild uptake, and multi-focus uptake groups (all P > 0.05). (2) In cases with SUVmax ≥2.5, the false-positive rate in the multi-focus uptake group was 83.3% (10/12), which was significantly higher than in the full uptake (12/75) or circular uptake group (7/23) (all P < 0.05). In cases with SUVmax <2.5, the false-negative rates in the mild and no-uptake groups were 41.7 and 17.6% (P = 0.218). (3) The sensitivity, specificity, accuracy, PPV, and NPV of the method using (18)F-FDG uptake features combined with SUVmax and the single SUV method were 88.7%/91.0%, 62.0%/42.0%, 79.1%/73.4%, 80.6%/73.6%, and 75.6%/72.4%, respectively. CONCLUSIONS: The method using uptake features of (18)F-FDG combined with SUVmax can improve the diagnostic specificity and accuracy of solitary pulmonary lesions. The multi-focus uptake feature maybe a benign sign, which still needs more researches to confirm.

Comparative study of phenolic compounds and antioxidant activity in different species of cherries.

A new spectrometric method ultra performance liquid chromatography-tandem mass spectrometric with high precision and rapid analysis was developed to separate 17 phenolic compounds. Different species of cherries, including 10 sweet cherry (Prunus avium L.) cultivars, a tart cherry (P. cerasus L.) rootstock (CAB), and a hybrid rootstock 'Colt' (P. avium × P. pseudocerasus), were analyzed for phenolics contents by this method. The results showed that significant differences were observed among the phenolic compound contents in different cherry species. In 10 sweet cherry cultivars, the contents of neochlorogenic acid and cyanidin-3O-rutinoside were much higher in red-colored fruits (for example, 64.60 and 44.50 mg/100 g fresh weight in Burlat, respectively) than those in bicolored ones. Principal component analysis revealed that cyanidin-3O-rutinoside was an effective index for grouping the cultivars with similar species and fruit colors. Moreover, there were strong positive correlations between phenolics content and antioxidant activity, which was higher in red-colored cherries.