Spatial transcriptomics reveals prognosis-associated cellular heterogeneity in the papillary thyroid carcinoma microenvironment.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common malignant endocrine tumour, and its incidence and prevalence are increasing considerably. Cellular heterogeneity in the tumour microenvironment is important for PTC prognosis. Spatial transcriptomics is a powerful technique for cellular heterogeneity study. METHODS: In conjunction with a clinical pathologist identification method, spatial transcriptomics was employed to characterise the spatial location and RNA profiles of PTC-associated cells within the tissue sections. The spatial RNA-clinical signature genes for each cell type were extracted and applied to outlining the distribution regions of specific cells on the entire section. The cellular heterogeneity of each cell type was further revealed by ContourPlot analysis, monocle analysis, trajectory analysis, ligand-receptor analysis and Gene Ontology enrichment analysis. RESULTS: The spatial distribution region of tumour cells, typical and atypical follicular cells (FCs and AFCs) and immune cells were accurately and comprehensively identified in all five PTC tissue sections. AFCs were identified as a transitional state between FCs and tumour cells, exhibiting a higher resemblance to the latter. Three tumour foci were shared among all patients out of the 13 observed. Notably, tumour foci No. 2 displayed elevated expression levels of genes associated with lower relapse-free survival in PTC patients. We discovered key ligand-receptor interactions, including LAMB3-ITGA2, FN1-ITGA3 and FN1-SDC4, involved in the transition of PTC cells from FCs to AFCs and eventually to tumour cells. High expression of these patterns correlated with reduced relapse-free survival. In the tumour immune microenvironment, reduced interaction between myeloid-derived TGFB1 and TGFBR1 in tumour focus No. 2 contributed to tumourigenesis and increased heterogeneity. The spatial RNA-clinical analysis method developed here revealed prognosis-associated cellular heterogeneity in the PTC microenvironment. CONCLUSIONS: The occurrence of tumour foci No. 2 and three enhanced ligand-receptor interactions in the AFC area/tumour foci reduced the relapse-free survival of PTC patients, potentially leading to improved prognostic strategies and targeted therapies for PTC patients.

Giant cellular leiomyoma in the broad ligament of the uterus: A case report.

BACKGROUND: The treatment of large pelvic masses in postmenopausal women is a challenge in clinical practice. Although ultrasound or magnetic resonance imaging can be used to determine the size and location of the mass, it is still difficult to achieve a preoperative diagnosis. The majority of cellular leiomyomas are diagnosed by histopathology after surgery. We report the differential diagnosis and surgical management of a rare case of cellular leiomyoma in the broad ligament of the uterus. CASE SUMMARY: A 52-year-old Chinese woman without sexual history was admitted to the First Affiliated Hospital of Guangzhou University of Chinese Medicine for the first time. The patient had a 1-year history of progressive abdominal enlargement as well as a 2-year history of menopause, and complained of frequent abdominal pain and low-grade fever. Computed tomography of the abdomen showed a solid cystic mass (29.4 cm × 18.8 cm × 37.7 cm) in the pelvis and abdomen. Moreover, routine blood test results indicated a baseline cancer antigen 125 (CA-125) level of 187.7 U/mL and C-reactive protein of 109.58 mg/L. Subsequently, retrograde hysterectomy and bilateral adnexectomy were performed in this patient. On histopathologic examination of the surgical specimen, a rare cellular leiomyoma in the broad ligament was diagnosed. CONCLUSION: Clinicians need to constantly improve diagnosis and treatment for the challenges posed during clinical assessment, differential diagnosis, and surgical management.

Differential distribution and prognostic value of CD4+ T cell subsets before and after radioactive iodine therapy in differentiated thyroid cancer with varied curative outcomes.

Differentiated thyroid cancer is the most frequently diagnosed endocrine tumor. While differentiated thyroid cancers often respond to initial treatment, little is known about the differences in circulating immune cells amongst patients who respond differently. A prospective study of 39 patients with differentiated thyroid cancer was conducted. Serum thyroglobulin levels and thyroid and immunological functions were tested before and after radioactive iodine treatment (RAIT). Efficacy assessments were performed 6 to 12 months after radioactive iodine treatment. Most patients showed an excellent response to radioactive iodine treatment. Before radioactive iodine treatment, the excellent response group had considerably fewer circulating CD4+ T cell subsets than the non-excellent response group. Both the excellent response and non-excellent response groups had considerably lower circulating CD4+ T lymphocyte subsets 30 days after radioactive iodine treatment, but those of the excellent response group were still lower than those of the non-excellent response group. All circulating CD4+ T cell subsets in the excellent response group rose by varying degrees by the 90th day, but only Treg cell amounts increased in the non-excellent response group. Interestingly, in the non-excellent response group, we noticed a steady drop in Th1 cells. However, the bulk of circulating CD4+ T cell subsets between the two groups did not differ appreciably by the 90th day. Finally, we discovered that CD4+ T cell subsets had strong predictive potential, and we thus developed high-predictive-performance models that deliver more dependable prognostic information. In conclusion, in individuals with differentiated thyroid cancer, there is great variation in circulating immune cells, resulting in distinct treatment outcomes. Low absolute CD4+ T cell counts is linked to improved clinical outcomes as well as stronger adaptive and resilience capacities.

A prospective trial to evaluate the clinical efficacy and safety of neoadjuvant chemotherapy with arsenic trioxide and carboplatin in locally advanced cervical cancer: a study protocol for randomized controlled clinical.

BACKGROUND: Cervical cancer is the fourth most common malignancy in women, which is threatening female reproductive tract health. Chemotherapy can be used for neoadjuvant therapy of locally advanced cervical cancer and postoperative adjuvant therapy for patients with high-risk factors, so as to reduce the focus, sensitize radiotherapy, and reduce recurrence. The current first-line treatment is paclitaxel combined with platinum. Many literature studies have found that As2O3 alone or in combination with platinum drugs have good efficacy in a variety of tumors both in vivo and in vitro. Moreover, our research group has verified that the efficacy of As2O3 combined with platinum drugs in the treatment of cervical cancer is not inferior to the traditional first-line regimen at the cellular and animal levels, and paclitaxel is more expensive than As2O3. Hence, we aim to evaluate the clinical efficacy and safety of neoadjuvant chemotherapy with As2O3 and carboplatin in locally advanced cervical cancer. METHODS: Sixty participants in the IB2, IIA2, and IIB stages of cervical cancer will be recruited in this study. After excluding patients who did not meet the criteria, they were randomly assigned to two groups in a 1:1 ratio. All patients underwent colposcopic biopsies to confirm the diagnosis and detailed clinical examinations. Eligible patients will receive either 2 cycles of paclitaxel and carboplatin or As2O3 and carboplatin every 3 weeks. Patients were assessed for clinical efficacy after the second cycle of chemotherapy. Patients who had disease stable or disease progression at these time points will receive concurrent chemotherapy and radiation directly, while responders will receive PiverRutledge grade III radical hysterectomy and bilateral pelvic lymphadenectomy. Both groups of patients undergoing radical hysterectomy were given adjuvant therapy as per protocol-defined criteria. The efficacy and toxicity of the two groups were evaluated according to WHO acute and subacute toxicity classification standards. DISCUSSION: This is the first single-center, prospective, two-arm design, open-label randomized control trial that will evaluate the clinical efficacy and safety of neoadjuvant chemotherapy with As2O3 and carboplatin in locally advanced cervical cancer. TRIAL REGISTRATION: ChineseClinicalTrialRegistry ChiCTR1900023822 . Registered on 13 June 2019.

Dynamic Immune Function Changes Before and After the First Radioactive Iodine Therapy After Total Resection of Differentiated Thyroid Carcinoma.

The effects of total thyroidectomy or radioactive iodine therapy on immune activation and suppression of the tumor microenvironment remain unknown. We aimed to investigate the effects of these treatments on the immune function in patients with differentiated thyroid carcinoma (DTC). Our cohort included 45 patients with DTC treated with total thyroidectomy and radioactive iodine therapy (RAIT). Immune function tests were performed by flow cytometry at 0, 30, and 90 days post-RAIT. Both the percentage and absolute number of circulating regulatory T cells were significantly lower in the postoperative DTC compared to the healthy controls. Notably, the absolute number of multiple lymphocyte subgroups significantly decreased at 30 days post-RAIT compared to those pre-RAIT. The absolute counts of these lymphocytes were recovered at 90 days post-RAIT, but not at pre-RAIT levels. Additionally, the Th17 cell percentage before RAIT was positively correlated with thyroglobulin (Tg) levels after RAIT. The tumor burden might contribute to increased levels of circulating Tregs. In conclusion, RAIT caused transient radiation damage in patients with DTC and the percentage of Th17 cells before RAIT could be a significant predictor of poor prognosis in patients with DTC.

Significance of DMBT1 in Papillary Thyroid Carcinoma Concurrent With Hashimoto's Thyroiditis.

BACKGROUND: Papillary thyroid carcinoma (PTC) concurrent with Hashimoto's thyroiditis (HT) was associated with a better clinical prognosis. This study aimed to investigate a potential mRNA gene that affects the development of PTC, which helps PTC concurrent with HT patients have a better prognosis. MATERIAL/METHODS: PTC data were obtained from The Cancer Genome Atlas (TCGA) database. And the validation data of tissue specimens were collected from Guangzhou First People's Hospital. The thyroid tissue sections were hybridized with deleted in malignant brain tumor 1 (DMBT1) probes by situ hybridization. Survival rates were analyzed using Kaplan-Meier curves, and the log-rank test was used to compare group survival rates. Prognosis clinicopathological factors were analyzed by Cox regression. Gene Ontology (GO) and Kyoto Gene and Genomic Encyclopedia (KEGG) pathway enrichment analyses were performed using single-sample gene set enrichment analysis (ssGSEA). Finally, the correlation of deletion in DMBT1 expression with overall immune status, tumor purity, and human leukocyte antigen (HLA) gene expression profile was analyzed. RESULTS: HT was significantly associated with sex, tumor foci, extrathyroidal extension (ETE), residual tumor, and tumor stage (T stage). Moreover, PTC concurrent with HT had a lower risk of recurrence versus non-HT groups. A total of 136 differentially expressed mRNAs (DEMs) were identified between HT and non-HT groups. Among them, the expression level of DMBT1 in HT groups was statistically higher than that in non-HT groups. A significant association with ETE and recurrence was revealed in the high expression and the low expression of DMBT1. Furthermore, DMBT1 was an independent predictor of survival. The overall immune activity of high expression of DMBT1 was higher than that of the low-expression group. CONCLUSIONS: The PTC patients with HT had better behavior features and prognosis than those with simple PTC. DMBT1 in PTC-HT patients was a potential possible factor that inhibits tumors. High expression of DMBT1 may improve PTC prognosis by immune-related pathways.

Effective tracking of bone mesenchymal stem cells in vivo by magnetic resonance imaging using melanin-based gadolinium3+ nanoparticles.

Tracking transplanted stem cells is necessary to clarify cellular properties and improve transplantation success. In this study, we designed and synthesized melanin-based gadolinium3+ (Gd3+ )-chelate nanoparticles (MNP-Gd3+ ) of ∼7 nm for stem cell tracking in vivo. MNP-Gd3+ possesses many beneficial properties, such as its high stability and sensitivity, shorter T1 relaxation time, higher cell labeling efficiency, and lower cytotoxicity compared with commercial imaging agents. We found that the T1 relaxivity (r1 ) of MNP-Gd3+ was significantly higher than that of Gd-DTPA; the nanoparticles were taken up by bone mesenchymal stem cells (BMSCs) via endocytosis and were broadly distributed in the cytoplasm. Based on an in vitro MTT assay, no cytotoxicity of labeled stem cells was observed for MNP-Gd3+ concentrations of less than 800 µg/mL. Furthermore, we tracked MNP-Gd3+ -labeled BMSCs in vivo using 3.0T MRI equipment. After intramuscular injection, MNP-Gd3+ -labeled BMSCs were detected, even after four weeks, by 3T MRI. We concluded that MNP-Gd3+ nanoparticles at appropriate concentrations can be used to effectively monitor and track BMSCs in vivo. MNP-Gd3+ nanoparticles have potential as a new positive MRI contrast agent in clinical applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 131-137, 2017.

[Influence of urea formaldehyde resin on pyrolysis of biomass: a modeling study by TG-FTIR].

Pyrolysis is an efficient and recycling way to utilize waste wood-based panels, in which urea-formaldehyde resin (UF) is the main difference between wood-based board and other kinds of biomass. The present paper studied the three main components (cellulose, hemicelluloses, lignin) of poplar wood, in order to effectively and environmentally utilize or dispose of waste wood-based panels with pyrolysis technique, to study the influence of urea formaldehyde resin on pyrolytic characteristic of wood during the process of the pyrolysis of waste wood-based panels, and to in-depth explore the mechanism of the effect of UF on each component of wood. Innovatively, the weight-loss character and gas evolution rule of the model (made from cellulose, xylan and lignin, based on the chemical components stud of poplar wood), the main components as well as the ones mixed with UF were analyzed by TG-FTIR (thermogravimetric analyzer coupled to a Fourier transform infrared spectrometer). Results indicated that UF promoted the generation of water and carboxylic acid substances during the cellulose pyrolysis process. UF combined with lignin, formed some kind of unstable nitrogenous structure which produced a large amount of NH3, which took part in the low-temperature (200-300 degrees C) pyrolysis of lignin, and directly affected the production of pyrolysis products. It can be concluded that during the process of the pyrolysis of waste wood-based panels, lignin was the one that UF mainly impacted among the three main components of wood.

[Radioiodine-131 therapy improves sex hormones and sexual function in male patients with Graves' disease].

OBJECTIVE: To observe the changes of sex hormones and sexual function in male patients with Graves' disease (GD) after Radioiodine-131 (I-131) therapy. METHODS: Thirty-four male GD patients, aged 21 -40 (32.3 +/- 6.7) years, were treated with I-131 at the dose of 111 - 407 (237.8 +/- 51.8) MBq. The levels of serum sex hormones were measured, and the patients'scores on erectile function (IIEF-5) were obtained before and 3 and 6 months after the treatment. Another 20 healthy men aged 25 - 37 (31 +/- 3.1) years were enlisted as controls. RESULTS: The baseline levels of estrogen (E2), testosterone (T) and luteinizing hormone (LH) were (132.5 +/- 40.4) pmol/L, (21.6 +/- 4.6) nmol/L and (10.1 +/- 4.4) IU/L in the GD patients, significantly higher than (80.4 +/- 31.2) pmol/L, (14.5 +/- 4.2) nmol/L and (6.2 +/- 1.9) IU/L in the healthy controls (P < 0.05). The E2, T and LH levels showed a significant decrease in the GD patients after 3 months of treatment ([110.2 +/- 20.6] pmol/L, [17.7 +/- 5.5] nmol/L and (9.4 +/- 3.9) IU/L, P < 0.05), but exhibited no statistically significant differences from the healthy controls at 6 months ([82.6 +/- 30.1] pmol/L, [13.8 +/- 3.4 ] nmol/L and [6.6 +/- 1.5] IU/L, P > 0.05). The IIEF-5 score of the GD patients was 5 - 25 (15.5 +/- 3.5) before I-131 treatment, significantly lower than that of the controls (19 - 25, 24 +/- 0.5) (P < 0.05), and it was 8 - 25 (19.5 +/- 1.0) at 3 months and 10 - 25 (23.5 +/- 1.5) at 6 months, significantly higher in the latter than in the former (P < 0.05), and with no significant difference between the 6-month treated patients and the healthy controls (P > 0.05). CONCLUSION: The E2, T and LH levels are increased while the IIEF-5 score decreased markedly in male GD patients. Six-month treatment with I-131 can not only restore the E2, T and LH levels to normal but also significantly improve the patient's sexual function.

[A comparative study of sentinel lymph node detection in laryngeal and hypopharyngeal carcinoma by lymphoscintigraphy method and blue dye].

OBJECTIVE: To investigate the clinical value of sentinel lymph node (SLN) detection in laryngeal and hypopharyngeal carcinoma patients with clinically negative neck (cN0) by lymphoscintigraphy method and blue dye. METHODS: Forty patients with cN0 laryngeal neoplasms and ten patients with cN0 hypopharyngeal carcinoma scheduled for tumor resection and neck dissection, were eligible for the study. single photon emission computed tomography (SPECT)/CT lymphoscintigraphy was performed with injection of radioactivity isotope 99Tc(m) labeled sulfur colloid (99Tc(m)-SC). Methylthioninium was injected into the same points as 99Tc(m)-SC during surgery, and the patients underwent lymphatic mapping with a handheld gamma-detecting probe. All removed lymph nodes were examined by routine histopathology. RESULTS: Thirty-five patients with laryngeal carcinoma and six patients with hypopharyngeal carcinoma detected SLN by radiolabeled tracer method, the detection rate of SLN was 82.0%. Twenty-nine patients with laryngeal carcinoma and 4 patients with hypopharyngeal carcinoma detected SLN by blue dye method, the detection rate of SLN was 66.0%. There were significant difference between two groups (chi² = 2.769, P < 0.05), and the number of SLN were respectively 96 and 83 by radiolabeled tracer method and blue dye (chi² = -2.098, P < 0.05), The sensitivity of SLN detection were respectively 83.3% and 66.7%. Twelve (24.0%) patients had lymph node metastasis. CONCLUSIONS: Either lymphoscintigraphy or blue dye mapping can be used to detect the SLN in cN0 laryngeal and hypopharyngeal carcinoma. The lymphoscintigraphy not only preoperatively can locate the accuracy of SLN detection, but also has higher detection rate and sensitivity than dye method.

[Significance of sentinel lymph node detection for cN0 laryngeal carcinoma].

OBJECTIVE: The purpose of this study was to investigate the clinical value of radiolabeled tracer method, methylene blue method and combination of these two methods in detection of sentinel lymph node (SLN), and to evaluate the accuracy of SLN in predicting the cervical lymph nodes status in laryngeal carcinoma patients with clinically negative neck lymph nodes (cN0 ). METHODS: Forty-one patients with cN0 laryngeal neoplasms underwent SLN detection using both of radiolabeled tracer and methylene blue. SLN imaging was performed with laryngoscope-guided injection of radioactive isotope 99Tc(m)-sulfur colloid (SC) into the laryngeal carcinoma before surgery, then all these patients underwent intraoperative lymphatic mapping with a handheld gamma-detecting probe. After mapping of SLN, methylene blue was subsequently injected at the same spots around the tumor in order to identify SLN during surgery. The results of SLN detection by isotope tracer, dye and combination of both methods were compared. RESULTS: The SLN detection rates by radiolabeled tracer, methylene blue and combined method were 87.8%, 70.7% and 92.7%, respectively (P < 0.01). The number of detected SLN was significantly different between radiolabeled tracer method and combined method (P < 0.05), and also between blue dye method and combined method (P < 0.01). However, no statistically significant difference was found between methylene blue method and radiolabeled tracer method (P > 0.05). Nine patients were found to have lymph node metastasis by final pathological examination. The sensitivity, accuracy and negative predictive values of SLN detection by the combined method using radiolabeled tracer and methylene blue were 88.9%, 97.4% and 96.7%, respectively. CONCLUSION: The combined method using radiolabeled tracer and methylene blue can improve the accuracy of sentinel lymph node detection. Furthermore, sentinel lymph node detection can accurately predict the cervical lymph node status in cN0 laryngeal carcinoma.