US of thyroid nodules: can AI-assisted diagnostic system compete with fine needle aspiration?

OBJECTIVES: Artificial intelligence (AI) systems can diagnose thyroid nodules with similar or better performance than radiologists. Little is known about how this performance compares with that achieved through fine needle aspiration (FNA). This study aims to compare the diagnostic yields of FNA cytopathology alone and combined with BRAFV600E mutation analysis and an AI diagnostic system. METHODS: The ultrasound images of 637 thyroid nodules were collected in three hospitals. The diagnostic efficacies of an AI diagnostic system, FNA-based cytopathology, and BRAFV600E mutation analysis were evaluated in terms of sensitivity, specificity, accuracy, and the κ coefficient with respect to the gold standard, defined by postsurgical pathology and consistent benign outcomes from two combined FNA and mutation analysis examinations performed with a half-year interval. RESULTS: The malignancy threshold for the AI system was selected according to the Youden index from a retrospective cohort of 346 nodules and then applied to a prospective cohort of 291 nodules. The combination of FNA cytopathology according to the Bethesda criteria and BRAFV600E mutation analysis showed no significant difference from the AI system in terms of accuracy for either cohort in our multicenter study. In addition, for 45 included indeterminate Bethesda category III and IV nodules, the accuracy, sensitivity, and specificity of the AI system were 84.44%, 95.45%, and 73.91%, respectively. CONCLUSIONS: The AI diagnostic system showed similar diagnostic performance to FNA cytopathology combined with BRAFV600E mutation analysis. Given its advantages in terms of operability, time efficiency, non-invasiveness, and the wide availability of ultrasonography, it provides a new alternative for thyroid nodule diagnosis. CLINICAL RELEVANCE STATEMENT: Thyroid ultrasonic artificial intelligence shows statistically equivalent performance for thyroid nodule diagnosis to FNA cytopathology combined with BRAFV600E mutation analysis. It can be widely applied in hospitals and clinics to assist radiologists in thyroid nodule screening and is expected to reduce the need for relatively invasive FNA biopsies. KEY POINTS: • In a retrospective cohort of 346 nodules, the evaluated artificial intelligence (AI) system did not significantly differ from fine needle aspiration (FNA) cytopathology alone and combined with gene mutation analysis in accuracy. • In a prospective multicenter cohort of 291 nodules, the accuracy of the AI diagnostic system was not significantly different from that of FNA cytopathology either alone or combined with gene mutation analysis. • For 45 indeterminate Bethesda category III and IV nodules, the AI system did not perform significantly differently from BRAFV600E mutation analysis.

Comparison of endoscopic thyroidectomy via the oral vestibule approach and the areola approach for papillary thyroid carcinoma.

BACKGROUND: The endoscopic thyroidectomy areola approach (ETAA) has been widely applied for papillary thyroid carcinoma (PTC), but leaves scars and is not truly minimally invasive. The oral vestibular approach (ETOVA) leaves no scars and is even more minimally invasive. However, there have been few comparative studies of ETAA and ETOVA for PTC. The purpose of our research was to compare two PTC treatment methods in terms of feasibility, safety, efficacy, and cosmetic results. METHODS: A total of 129 patients with PTC underwent thyroidectomy combined with central lymph node dissection by the same surgeon. Among them, 79 patients underwent the ETOVA, and the others underwent the ETAA. We compared the two groups in terms of operative outcomes, postoperative complications, and cosmetic results. RESULTS: No significant differences were found in the clinical characteristics between the ETOVA and ETAA groups. There were no significant differences in the number of removed lymph nodes (P = 0.279) or the number of positive lymph nodes (P = 0.569), but the ETOVA group had a higher number of removed lymph nodes. There was also no significant difference in blood loss volume(P = 0.180), postoperative drainage volume (P = 0.063), length of hospital stay (P = 0.182), transient RLN injury rate (P = 1.000), permanent RLN injury rate (P = 1.000), or recurrence rate (P = 1.000). The ETOVA was a longer operation than the ETAA was (P < 0.01). The ETOVA group had less pain (VAS 1: P < 0.01, VAS 3: P = 0.001), less neck discomfort (1 month after surgery: P = 0.009, 3 months after surgery: P = 0.033), and better cosmetic results (P = 0.001). CONCLUSIONS: The ETOVA is not inferior to the ETAA in terms of safety and curability of PTC and is advantageous in terms of central lymph node dissection, minimal invasiveness, and cosmetic results. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Zhongshan Hospital of Xiamen University (2017 V1.0). No funding was received.

Wu's seven steps for endoscopic central and lateral neck dissection via breast combined with oral approach for papillary thyroid cancer.

OBJECTIVE: We had previously reported endoscopic central and lateral neck dissection via breast combined with an oral approach for papillary thyroid cancer treatment. In this study, we optimized the procedure with Wu's seven steps to make the procedure quicker and easier. METHODS: Wu's seven steps for endoscopic central and lateral neck dissection via breast combined with oral approach for papillary thyroid cancer are: (1) establish the working space, (2) isolate the sternocleidomastoid and internal jugular vein, (3) dissect the thyroid via breast approach, (4) dissect the central lymph nodes via oral approach, (5) dissect the inferior board of level IV via oral approach, (6) remove the tissues of levels IV, III, and II via breast approach, and (7) wash the working space and place drainage tubes. Twelve patients were assigned to the Wu's seven steps group, and 13 patients were assigned to the contrast group. The operative procedure of the contrast group was the same as Wu's seven steps except for a few key differences, such as that the central lymph nodes were dissected via breast approach first and the internal jugular vein(IJV) was dissected from the cricoid cartilage down to the venous angle. RESULTS: The Wu's seven steps group had a short operation time and few injuries of the internal jugular vein. There were no statistical differences in other clinicopathological features or surgical complications. CONCLUSION: It appears that Wu's seven steps for endoscopic central and lateral neck dissection via breast combined with oral approach for papillary thyroid cancer are effective and safe.

Prospective, randomized, controlled, noninferiority clinical trial to evaluate the safety and efficacy of absorbable macroporous polysaccharide composites as adjunct to hemostasis during open surgery.

BACKGROUND: To address intraoperative bleeding in cardiac surgery, reducing blood transfusion requirements, is mandatory to achieve effective hemostasis. Hemostatic agents may limit localized persistent bleeding. The introduction of carboxymethyl-chitosan component into the hemostatic agent and the application of the radiation crosslinking technique maintain its capacity for achieving intraoperative hemostasis, thus increasing the clinical utility. METHODS: A prospective, noninferiority and randomized controlled clinical trial to compare the safety and efficacy of absorbable macroporous polysaccharide composites (AMPC, treatment group) with compound microporous polysaccharide hemostatic powder (CMPHP, control group) (2:1 ratio) as adjuncts to hemostasis in open surgery. The main indication was used for hemostasis in various traumatic hemorrhage areas, including cardiothoracic, vascular, and general surgery. The primary endpoint was success rate of hemostasis within 300 s (at a 10% noninferiority margin). The secondary endpoint was hemostasis time. Both endpoints were assessed in the modified intention-to-treat (MITT) population. Safety parameters were assessed. This study is fully compliant with the CONSORT statement. RESULTS: Randomized patients in AMPC and CMPHP groups were 168 and 84, respectively. In MITT population, the success rates of hemostasis within 300 s were 98.8% (163 of 165) in AMPC and 94.0% (78 of 83) in CMPHP (treatment difference 4.8% [95% CI -0.57% to 10.20%]). AMPC was thus noninferior to CMPHP. Hemostasis time (median [interquartile range]) with AMPC (87 [52.5, 180] s) was better than CMPHP (110 [54.5, 181] s). Changes in laboratory parameters over time and shifts to abnormal values were typical of surgeries and similar between two groups. No noticeable adverse effects associated with AMPC or CMPHP were observed. CONCLUSIONS: AMPC is well tolerated as topical hemostatic agent, noninferior to commercial CMPHP, and exhibits excellent safety. This study provides a novel hemostatic agent which appears to offer significant clinical advantage in various hemorrhage areas.

Circular RNA circHECTD1 prevents Diosbulbin-B-sensitivity via miR-137/PBX3 axis in gastric cancer.

BACKGROUNDS: Gastric cancer (GC) is general disease in human digestive system with malignancy. Emerging findings indicated that hsa_circ_0031452 (circHECTD1) was strictly associated with carcinogenesis. Nevertheless, the role of circHECTD1 in drug-resistance still needed to be explained. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to examine the expression profiles of circHECTD1, microRNA (miR)-137, and pre-leukemia transcription factor 3 (PBX3). The function of circHECTD1 in tumorigenesis was evaluated via xenograft tumor model. The IC50 of Diosbulbin-B (DB) was detected using Cell Counting Kit-8 (CCK8). Cell-cycle and apoptosis were reckoned by flow cytometry. Besides, western blot was administrated to reckon the levels of PBX3 and cell apoptotic indicators. Moreover, the interrelation between miR-137 and circHECTD1 or PBX3 was expounded by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull down assays. RESULTS: We uncovered that circHECTD1 was ectopically up-regulated in GC tissues and cells. CircHECTD1 deficiency sensitized DB-treatment in DB-evoked AGS and HGC-27 cells. In vivo assay, circHECTD1 silencing led to the tumor reduction. Also, circHECTD1 served as miR-137 sponge in a sequence-complementary manner. Furthermore, transfection of miR-137 inhibitor markedly eliminated circHECTD1 absence-mediated promotion of DB-sensitivity in GC cells. Moreover, PBX3, a target of miR-137, play a DB-resistant role in GC cells. Fascinatingly, the deletion of PBX3 reversed the impact of miR-137 repression and circHECTD1 knockdown on DB-sensitivity in vitro. CONCLUSIONS: CircHECTD1 served as an oncogene by a novel miR-137/PBX3 axis, which might supply an underlying biomarker for the diagnosis and prognosis of GC management.

Neural monitoring during ultrasound-guided radiofrequency ablation of thyroid nodules.

BACKGROUND: Intraoperative neurological monitoring is important in locating and assessing nerves during surgery. This study aimed to investigate the feasibility of neural monitoring during ultrasound-guided radiofrequency ablation (RFA) of thyroid nodules. METHODS: From February 2019 to August 2019, 16 patients (age, 42.8 ± 15.9 years; range, 17-74 years) with benign thyroid nodules who underwent ultrasound-guided RFA with neural monitoring in Zhongshan Hospital, Xiamen University, were included. A neuromonitoring system stimulated the vagus nerve to obtain electromyographic (EMG) signals and predict the function of recurrent laryngeal nerves (RLNs) during RFA. The hydrodissection technique was used to protect the RLN area. Thyroid nodules were treated with the moving-shot technique. The EMG signal value results were recorded and analyzed. All patients underwent laryngoscopic investigation 1 day after the procedure. RESULTS: Twenty vagus nerves were stimulated preprocedure and postprocedure, and the EMG signals were successfully recorded (100%). The mean initial (before ablation) and final (final ablation) vagus nerve amplitudes were 612.7 ± 130.4 µV (range, 455-882 µV) and 592.7 ± 127.3 µV (range, 410-817 µV), respectively. Based on the EMG signals, all 20 RLNs were judged to be in good condition, consistent with the postprocedure laryngoscopic results. The maximum lesion size and volume at 6 months after RFA were significantly lesser than those at baseline (p < 0.05). The volume reduction rate was 68.5% ± 21.5% (range, 13.0-97.3%). Cosmetic and symptom scores were significantly lower than those at baseline. No complications from neural monitoring occurred. CONCLUSIONS: Neural monitoring during ultrasound-guided RFA of thyroid nodules is feasible to predict RLN function.

ProGRP AS A NOVEL BIOMARKER FOR THE DIFFERENTIAL DIAGNOSIS OF MEDULLARY THYROID CARCINOMA IN PATIENTS WITH THYROID NODULES.

Objective: To investigate the release of progastrin-releasing peptide (ProGRP) in patients with thyroid nodules and the value of ProGRP in fine-needle aspirate washout fluid (FNA-ProGRP) in the differential diagnosis between medullary thyroid carcinoma (MTC) and non-MTC thyroid nodules. Methods: We investigated 2,446 healthy persons and 212 patients with 235 thyroid nodules. They were classified into healthy, nodular goiter, chronic thyroiditis, thyroid follicular neoplasm, papillary thyroid carcinoma, follicular thyroid carcinoma, and medullary thyroid carcinoma. The serum ProGRP and FNA-ProGRP were measured. Results: The serum ProGRP median concentration in MTC was 124.40 pg/mL, significantly higher than in other groups. The cutoff value of serum ProGRP was 68.30 pg/mL, leading to 53.85% sensitivity, 96.98% specificity, and 0.51 kappa value in MTC. The FNA-ProGRP median concentration in MTC nodules was 2,096.00 pg/mL, significantly higher than in other groups. A receiver operating characteristic analysis of MTC nodules and non-MTC nodules indicated that the cutoff value was 22.77 pg/mL, leading to 94.12% sensitivity, 98.27% specificity, and 0.85 kappa value. Conclusion: FNA-ProGRP measurement could be served as an ancillary method for the differential diagnosis between MTC and non-MTC thyroid nodules. Abbreviations: CEA = carcinoembryonic antigen; CT = calcitonin; FNAC = fine-needle aspiration cytology; FNA-CT = calcitonin in fine-needle aspirate washout fluid; FNA-ProGRP = ProGRP in fine-needle aspirate washout fluid; MTC = medullary thyroid carcinoma; ProGRP = progastrin-releasing peptide; SCLC = small-cell lung cancer; TM = tumor marker.

Katanin P60 and P80 in papillary thyroid carcinoma patients: Indicators for exacerbated tumor features and worse disease-free survival.

BACKGROUND: This study aimed to explore the clinical implications of katanin P60 and P80 (katanin P60/P80) regarding their correlations with clinicopathological features and survival profiles in papillary thyroid carcinoma (PTC) patients. METHODS: Tumor tissue and paired adjacent tissue specimens were obtained from 172 PTC patients who underwent lobectomy or thyroidectomy. Besides, immunohistochemistry assay and immunoreactive (IR) score (multiplying staining intensity score by density score) were used to determine katanin P60/P80 expressions. According to IR score (from 0 ~ 12), katanin P60/P80 expressions were classified as low (IR score 0 ~ 3) and high (IR score 4 ~ 12) expressions. RESULTS: Both katanin P60/P80 expressions were highly expressed in tumor tissue compared with adjacent tissue. Besides, tumor katanin P60 expression positively correlated with tumor katanin P80 expression. Tumor katanin P60 high expression correlated with larger tumor size, extrathyroidal invasion, advanced pT stage, pN stage, and pTNM stage, while no correlation of tumor katanin P60 expression with age or gender was observed; tumor katanin P80 high expression correlated with advanced pN stage and pTNM stage, whereas there was no correlation of tumor katanin P80 expression with age, gender, tumor size, extrathyroidal invasion, or pT stage. Furthermore, both tumor katanin P60/P80 high expressions correlated with shorter accumulating disease-free survival. As for overall survival (OS), neither tumor katanin P60 nor P80 expression correlated with OS. CONCLUSION: Katanin P60/P80 measurement might assist with tumor management and prognosis surveillance in PTC patients.

Endoscopic Central Lymph Node Dissection via Breast Combined with Oral Approach for Papillary Thyroid Carcinoma: A Preliminary Study.

OBJECTIVE: To investigate the feasibility and necessity of endoscopic thyroidectomy with central lymph node dissection via the combined breast and trans-oral approaches. METHODS: Six patients with papillary thyroid carcinoma who underwent endoscopic total thyroidectomy with central node dissection via combined breast and trans-oral approaches from November 2014 to January 2015 in Zhongshan Hospital, Xiamen University, were analyzed. RESULTS: After completion of endoscopic central lymph node dissection via the traditional breast approach, eight pieces of lymph nodes could still be dissected via the trans-oral approach. Two of these eight pieces were positive for thyroid cancer metastasis. CONCLUSIONS: It is advisable to perform endoscopic central lymph node dissection for thyroid carcinoma via the breast approach combined with the trans-oral approach.

[Reversal of stemness in multidrug-resistant hepatocellular carcinoma cells by SIS3].

OBJECTIVE: To investigate whether SIS3, a specific inhibitor of Smad3 phosphorylation, can reverse the stemness of multidrug-resistant(MDR) hepatocellular carcinoma cells. METHODS: MDR HCC Huh7.5.1/ADM cell lines were developed by exposing parental cells to stepwise increasing concentrations of ADM. CCK-8 assay was used to determine the cellular sensitivity of various anticancer drugs. Flow cytometry (FCM) was used to analyze the expression level of cancer stem cell marker CD133. Clone formation assay and mouse subcutaneous xenograft tumors were used to investigate the tumorigenicity in vitro and in vivo. Western blotting (WB) was used to analyze the changes of expressions of CD133, Smad3, Bcl-2, Bax and p-Smad3 in different conditions. RESULTS: ADM treatment of HCC cells in vitro resulted in a development of subline, Huh7.5.1/ADM cells, with CSC phenotypes: stable MDR phenotype (besides ADMc Huh7.5.1/ADM cells were also more resistant to some other anticancer drugs including VCR, MMC and CTX ) (IC50: 0.215 ± 0.018 vs. 0.123 ± 0.004, 0.145 ± 0.009 vs. 0.014 ± 0.002, 1.021 ± 0.119 vs. 0.071 ± 0.006, 27.007 ± 1.606 vs. 1.919 ± 0.032) (unit: µg/ml) (P<0.05). Huh7.5.1/ADM cells enriched the cancer stem-like cell fraction (CD133-positive subpopulation) (76.06 ± 2.948% vs. 25.38 ± 4.349%) (P<0.05), had stronger tumorigenicity in vivo and colony formation ability, and activated the Smad3 activity. Inhibition of Smad3 activity by SIS3 decreased stemness of the Huh7.5.1/ADM cells: CD133-positive subpopulation (48.49 ± 2.304% vs. 76.06 ± 2.948%) (P<0.05); ADM IC50: (0.112 ± 0.019 vs. 0.215 ± 0.018), VCR IC50 (0.065 ± 0.013 vs. 0.145±0.009), MMC IC50 (0.749 ± 0.121 vs. 1.021 ± 0.119), CTX IC50 (10.576 ± 1.248 vs. 27.007 ± 1.606) (unit: µg/ml) (P<0.05), and decreased tumorigenicity and colony formation ability. CONCLUSION: SIS3 as a specific inhibitor of Smad3 signal is involved in the stemness of multidrug resistant hepatocellular carcinoma cells.

Cancer-associated fibroblast-derived periostin promotes papillary thyroid tumor growth through integrin-FAK-STAT3 signaling.

Background: Periostin (POSTN) is a critical extracellular matrix protein in various tumor microenvironments. However, the function of POSTN in thyroid cancer progression remains largely unknown. Methods: Postn and Rag1 knock-out mice and orthotopic mouse models were used to determine the role of POSTN on papillary thyroid tumor progression. Immunofluorescence, cell co-culture, fluorescence in situ hybridization, chromatin immunoprecipitation assay, recombinant protein and inhibitor treatment were performed to explore the underlying mechanisms of POSTN-promoted papillary thyroid tumor growth. Results: POSTN is up-regulated in papillary thyroid tumors and negatively correlates with the overall survival of patients with thyroid cancer. Cancer-associated fibroblast (CAF)-derived POSTN promotes papillary thyroid tumor growth in vivo and in vitro. POSTN deficiency in CAFs significantly impairs CAF-promoted papillary thyroid tumor growth. POSTN promotes papillary thyroid tumor cell proliferation and IL-4 expression through integrin-FAK-STAT3 signaling. In turn, tumor cell-derived IL-4 induces the activation of CAFs and stimulates POSTN expression by activating STAT6. We reveal the crucial role of CAF-derived POSTN and tumor cell-derived IL-4 in driving the development of papillary thyroid tumors through the POSTN-integrin-FAK-STAT3-IL-4 pathway in tumor cells and IL-4-STAT6-POSTN signaling in CAFs. Conclusion: Our findings underscore the significance of POSTN and IL-4 as critical molecular mediators in the dynamic interplay between CAFs and tumor cells, ultimately supporting the growth of papillary thyroid tumors.

[Metformin induces apoptosis in hepatocellular carcinoma Huh-7 cells in vitro and its mechanism].

OBJECTIVE: to investigate the effects of antidiabetic drug metformin on proliferation and apoptosis in human hepatocellular carcinoma cell line Huh-7 cells. METHODS: Huh-7 cells were treated with metformin at different concentrations. Cell viability was determined by MTT assay. Cell apoptosis and CD133(+) expression rate were detected by flow cytometery (FCM). Expressions of PTEN, Akt, p-Akt, Bcl-2, Bax proteins in the cells were measured by Western blot. The effect of metformin on the hepatosphere formation was observed in the serum-free suspension culture. Reverse transcription-polymerase chain reaction (RT-PCR) was used to validate the expression levels of stemness marker genes CD133, ß-catenin, and ABCG2 mRNA in the hepatospheres. RESULTS: The proliferation of Huh-7 cells was inhibited by metformin in a dose- and time-dependent manner. The early and late cell apoptosis rates induced by metformin at dose of 10 mmol/L for 48 hrs were (22.29 ± 0.8)% and (13.87 ± 1.2)%, respectively, and 25 mmol/L for 48 hrs (15.28 ± 2.1)% and (25.89 ± 2.3)%, respectively. Western blotting results revealed that the expression of CD133, phosphorylated Akt and the Bcl-2/Bax ratio were downregulated, and PTEN was upregulated in the Huh-7 cells after treated with 25 mmol/L metformin for 48 hrs. Metformin inhibited the formation of hepatospheres. Metformin also downregulated the expression of several cancer stem cells (CSCs)-related genes which are involved in the signaling pathways governing the self-renewal, proliferation and differentiation of CSCs in the hepatospheres. CONCLUSIONS: Metformin inhibits the proliferation of human hepatocellular carcinoma Huh-7 cells and enhances their apoptosis in vitro. It may be related to the downregulation of PI3K/Akt signal pathway and selectively targeting CD133(+) cells.

Transoral endoscopic thyroid surgery via vestibular approach with silastic chin augmentation genioplasty.

From July 2020 to March 2022, 3 patients with papillary thyroid cancer (PTC) and microgenia underwent transoral endoscopic thyroid surgery via a vestibular approach or a endoscopic lateral neck dissection via the breast and transoral approaches with chin silastic augmentation genioplasty performed concurrently. Image documentation, patient satisfaction, complications and other factors such as demographics and clinicopathologic details were recorded. None of the patients developed major complications and there were no complications such as infection or displacement of the implant. All patients were satisfied with the cosmetic outcomes. Despite the study being limited to these 3 selected patients with PTC and microgenia, the follow-up to our initial description of the new technique established its safety and efficacy.

Exploring the Therapeutic Potential of Ethyl 3-Hydroxybutyrate in Alleviating Skeletal Muscle Wasting in Cancer Cachexia.

Cachexia (CAC) is a debilitating metabolic syndrome. Although dietary interventions are attractive, long-term adherence to specific diets is difficult to maintain and can lead to systemic side effects. Ethyl 3-hydroxybutyrate (EHB) is a commonly used food additive found in wine and Tribolium castaneum. In this study, we investigated the effects of EHB administration in cachectic mice. After a single intraperitoneal injection of EHB into mice, 3-hydroxybutyrate (3-HB) levels were significantly increased in the serum and gastrocnemius of mice. The administration of EHB alleviated cachexia-related symptoms, ameliorated skeletal muscle atrophy, and improved survival in cachectic mice. In addition, the supplementation of cachectic mice with 3-HB by EHB administration significantly reduced tumor weights, indicating the anti-tumor effects of 3-HB. Remarkably, the addition of 3-HB to the culture medium significantly attenuated the C2C12 myotube atrophy induced by the culture supernatant of CT26 cell lines, highlighting its potential to counteract the destructive effects of tumor-derived elements on muscle tissue. NMR-based metabolomics analysis provided insights into the underlying mechanisms and revealed that the anti-cachexia effects of 3-HB treatment can be attributed to three key mechanisms: the promotion of the TCA cycle and the attenuation of proteolysis, the promotion of protein synthesis and the improvement of metabolic homeostasis, and a reduction in inflammation and an enhancement of the antioxidant capacity. This study provided compelling evidence for the protective effects of 3-HB treatment on the cachectic gastrocnemius and highlighted the efficacy of EHB administration as a ketone supplementation approach to achieve nutritional ketosis without the need for dietary restriction.

Performance of CT-based deep learning in diagnostic assessment of suspicious lateral lymph nodes in papillary thyroid cancer: a prospective diagnostic study.

BACKGROUND: Preoperative evaluation of the metastasis status of lateral lymph nodes (LNs) in papillary thyroid cancer is challenging. Strategies for using deep learning to diagnosis of lateral LN metastasis require additional development and testing. This study aimed to build a deep learning-based model to distinguish benign lateral LNs from metastatic lateral LNs in papillary thyroid cancer and test the model's diagnostic performance in a real-world clinical setting. METHODS: This was a prospective diagnostic study. An ensemble model integrating a three-dimensional residual network algorithm with clinical risk factors available before surgery was developed based on computed tomography images of lateral LNs in an internal dataset and validated in two external datasets. The diagnostic performance of the ensemble model was tested and compared with the results of fine-needle aspiration (FNA) (used as the standard reference method) and the diagnoses made by two senior radiologists in 113 suspicious lateral LNs in patients enrolled prospectively. RESULTS: The area under the receiver operating characteristic curve of the ensemble model for diagnosing suspicious lateral LNs was 0.829 (95% CI: 0.732-0.927). The sensitivity and specificity of the ensemble model were 0.839 (95% CI: 0.762-0.916) and 0.769 (95% CI: 0.607-0.931), respectively. The diagnostic accuracy of the ensemble model was 82.3%. With FNA results as the criterion standard, the ensemble model had excellent diagnostic performance ( P =0.115), similar to that of the two senior radiologists ( P =1.000 and P =0.392, respectively). CONCLUSION: A three-dimensional residual network-based ensemble model was successfully developed for the diagnostic assessment of suspicious lateral LNs and achieved diagnostic performance similar to that of FNA and senior radiologists. The model appears promising for clinical application.

HIV and HCV cooperatively promote hepatic fibrogenesis via induction of reactive oxygen species and NFkappaB.

HIV/HCV coinfection leads to accelerated hepatic fibrosis progression, with higher rates of cirrhosis, liver failure, and liver death than does HCV mono-infection. However, the profibrogenic role of HIV on hepatocytes and hepatic stellate cells (HSC) has not been fully clarified. We hypothesized that HIV, HCV induce liver fibrosis through altered regulation of the production of extracellular matrix and matrix metalloproteinases. We examined the fibrogenesis- and fibrolysis-related gene activity in LX2 HSC and Huh7.5.1 cells in the presence of inactivated CXCR4 and CCR5 HIV, as well as HCV JFH1 virus. The role of reactive oxygen species (ROS) upon fibrosis gene expression was assessed using the ROS inhibitor. Fibrosis-related transcripts including procollagen α1(I) (CoL1A), TIMP1, and MMP3 mRNA were measured by qPCR. TIMP1 and MMP3 protein expression were assessed by ELISA. We found that inactivated CXCR4 HIV and CCR5 HIV increased CoL1A, and TIMP1 expression in both HSC and Huh7.5.1 cells; the addition of JFH1 HCV further increased CoL1A and TIMP1 expression. CXCR4 HIV and CCR5 HIV induced ROS production in HSC and Huh7.5.1 cells which was further enhanced by JFH1 HCV. The ROS inhibitor DPI abrogated HIV-and HCV-induced CoL1A and TIMP1 expression. HIV and HCV-induced CoL1A and TIMP1 expression were also blocked by NFκB siRNA. Our data provide further evidence that HIV and HCV independently regulate hepatic fibrosis progression through the generation of ROS; this regulation occurs in an NFκB-dependent fashion. Strategies to limit the viral induction of oxidative stress are warranted to inhibit fibrogenesis.

Initial Experience With Transoral Endoscopic Thyroidectomy via the Submental and Vestibular Approach for the Treatment of Thyroid Cancer: A Retrospective Cohort Study.

Background: Transoral endoscopic thyroidectomy vestibular approach is feasible and safe but has some unavoidable limitations, such as sensory changes in the center of the chin region. We aim to report our initial experience in performing transoral endoscopic thyroidectomy via the submental and vestibular approach for the treatment of thyroid cancer. Patients and Methods: This retrospective cohort study included patients with thyroid cancer confirmed by fine-needle aspiration who underwent endoscopic thyroidectomy and central lymph node dissection via the submental and vestibular approaches between November 2019 and January 2020. Patients' clinicopathological characteristics, operation details, and postoperative complications were analyzed. Results: Fifteen surgeries were performed successfully. The mean ± standard deviation age of the patients was 37 ± 10.8 years, the average duration of surgery was 146.5 ± 34.6 min, and the median intraoperative blood loss was 11.1 ± 6.3 mL. None of the surgeries were converted to open thyroidectomy. According to postoperative pathology, all cases involved papillary thyroid carcinoma or papillary thyroid microcarcinoma. One patient developed transient recurrent laryngeal nerve paralysis. No patient developed skin numbness at the center of the chin region. Conclusions: Transoral endoscopic thyroidectomy via the submental and vestibular approach is effective and safe in patients with thyroid cancer and does not lead to skin numbness at the center of the chin region. This technique is beneficial for surgeons less experienced in performing transoral thyroid surgery as it involves using a short and direct route to the thyroid gland, which can reduce the difficulty in establishing the first operative space to some extent.

Endoscopic lateral neck dissection via the breast and transoral approaches for papillary thyroid carcinoma: A preliminary report.

Purpose: Complete lymph node dissection is essential for the management of papillary thyroid carcinoma (PTC) with lymph node metastasis (LNM). This work aimed to describe the feasibility of endoscopic lateral neck dissection via the breast and transoral approach (ELNDBTOA) in PTC patients and the necessity of the addition of the transoral approach. Methods: We included 13 patients with PTC and suspected lateral LNM who underwent ELNDBTOA at the Zhongshan Hospital, Xiamen University. Total thyroidectomy, ipsilateral central lymph node dissection, and selective neck dissection (levels IIA, IIB, III, and IV) were performed endoscopically via the breast approach. Residual lymph nodes were further dissected via the transoral approach. Results: The mean operation time was 362.1 ± 73.5 min. In the lateral neck compartments, the mean number of retrieved lymph nodes was 36.6 ± 23.8, and the mean number of positive lymph nodes was 6.8 ± 4.7. In further dissection via the transoral approach, lymph nodes in the lateral neck compartment were obtained in nine patients (9/13, 69.2%), and three patients (3/13, 23.1%) had confirmed lateral neck metastases. Transient hypocalcemia occurred in two patients (2/13, 15.4%), and three patients (3/13, 23.1%) developed transient skin numbness in the mandibular area. No other major complications were observed. There was no evidence of local recurrence or distant metastasis during the follow-up period (range, 24-87 months). All patients were satisfied with the good cosmetic outcome. Conclusion: ELNDBTOA is an option with proven feasibility for select PTC patients with LNM, and the addition of the transoral approach is necessary to ensure complete dissection.

Hepatitis C virus regulates transforming growth factor beta1 production through the generation of reactive oxygen species in a nuclear factor kappaB-dependent manner.

BACKGROUND & AIMS: The generation of oxidative stress and transforming growth factor beta1 (TGF-beta1) production play important roles in liver fibrogenesis. We have previously shown that hepatitis C virus (HCV) increases hepatocyte TGF-beta1 expression. However, the mechanisms by which this induction occurs have not been well studied. We explored the possibility that HCV infection regulates TGF-beta1 expression through the generation of reactive oxygen species (ROS), which act through > or =1 of the p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor kappaB (NFkappaB) signaling pathways to induce TGF-beta1 expression. METHODS: We used small molecule inhibitors and short interfering RNAs to knock down these pathways to study the mechanism by which HCV regulates TGF-beta1 production in the infectious JFH1 model. RESULTS: We demonstrated that HCV induces ROS and TGF-beta1 expression. We further found that JFH1 induces the phosphorylation of p38MAPK, JNK, ERK, and NFkappaB. We also found that HCV-mediated TGF-beta1 enhancement occurs through a ROS-induced and p38 MAPK, JNK, ERK1/2, NFkappaB-dependent pathway. CONCLUSIONS: These findings provide further evidence to support the hypothesis that HCV enhances hepatic fibrosis progression through the generation of ROS and induction of TGF-beta1. Strategies to limit the viral induction of oxidative stress appear to be warranted to inhibit fibrogenesis.

Inhibition of circRNA circVPS33B Reduces Warburg Effect and Tumor Growth Through Regulating the miR-873-5p/HNRNPK Axis in Infiltrative Gastric Cancer.

BACKGROUND: Circular RNA VPS33B (circVPS33B) has been revealed to be upregulated in gastric cancer (GC) tissues. However, the role of circVPS33B in infiltrative GC is indistinct. METHODS: Expression of circVPS33B was detected using quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, and invasion of infiltrative GC cells (XGC-1) were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT), plate clone, wound-healing, or transwell assays. Protein levels were detected by Western blotting. Measurements of extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were executed using an XF96 extracellular flux analyzer. Glucose uptake and lactate production were analyzed by glycolysis assay. The regulatory mechanism of circVPS33B had been explored by bioinformatics analysis, dual-luciferase reporter assay, and/or RNA pull-down assay. In vivo tumorigenesis assay was executed to verify the oncogenicity of circVPS33B. RESULTS: CircVPS33B was upregulated in infiltrative GC tissues and cells. CircVPS33B silencing decreased tumor growth in vivo and inhibited proliferation, migration, invasion, EMT, and Warburg effect of infiltrative GC cells in vitro. Mechanically, circVPS33B regulated heterogeneous nuclear ribonucleoprotein K (HNRNPK) expression via sponging miR-873-5p. Furthermore, miR-873-5p inhibitor offset circVPS33B knockdown-mediated effects on malignant behaviors and Warburg effect of infiltrative GC cells. HNRNPK overexpression reversed the inhibitory impact of miR-873-5p mimic on malignant behaviors and Warburg effect of infiltrative GC cells. CONCLUSION: CircVPS33B accelerated Warburg effect and tumor growth through regulating the miR-873-5p/HNRNPK axis in infiltrative GC, manifesting that circVPS33B might be a potential target for infiltrative GC treatment.