[Controversy and boundary in the diagnose and treatment of thyroid cancer].

In recent years, the incidence of thyroid cancer has rapidly increased, whereas the mortality rate has not risen correspondingly. Therefore, scholars at home and abroad have proposed the view of overdiagnosis in thyroid cancer, sparking intense debates about the phenomenon of overdiagnosis and overtreatment. A historical review and discussion of the primary reasons for the increase in thyroid cancer incidence and the improvement in treatment outcomes are beneficial. It helps clarify that the real increase in thyroid cancer is primarily due to the higher incidence rate, rather than overdiagnosis. Additionally, it allows us to reevaluate which factors guarantee favorable efficacy in thyroid cancer.

A national study of postoperative thyroid hormone supplementation rates after thyroid lobectomy.

BACKGROUND: The American Thyroid Association updated guidelines in 2015 to allow lobectomy for low-risk thyroid cancers. The objectives of this study were (1) to determine thyroid hormone supplementation rates after lobectomy and (2) to evaluate the effect of the American Thyroid Association guideline change on lobectomy and hormone supplementation rates among thyroid cancer patients. METHODS: The Merative MarketScan Databases was used to identify adult (≥age 18) patients who underwent thyroidectomy for benign nodules or thyroid cancer. The association between indication for surgery and postoperative thyroid hormone supplementation was examined using χ2 analyses and multivariable logistic regression models. Among patients with thyroid cancer, lobectomy and hormone supplementation rates were compared in the periods before (2008-2015) and after the guideline change (2016-2019). RESULTS: Of the 81,926 patients identified, 33,756 (41.2%) underwent thyroid lobectomy, 45,104 (55.1%) underwent total thyroidectomy, and 3,066 (3.7%) underwent completion thyroidectomy. Patients who underwent lobectomy for malignancy were significantly more likely to require hormone supplementation (59.3% vs 39.4% [P < .001], adjusted odds ratio 2.34 [95% confidence interval 2.20-2.48]) compared to those with benign disease. Compared to the 2008 to 2015 period, the proportion of patients who underwent lobectomy for thyroid cancer was higher in the 2016 to 2019 period (34.3% vs 30.3%, P < .001), with fewer patients requiring completion thyroidectomy (25.6% vs 29.8%, P < .001) and thyroid hormone supplementation (56.9% vs 60.1%, P = .04). CONCLUSION: The postoperative thyroid hormone supplementation rate was significantly higher in patients who had thyroid cancers compared to benign diseases. After the American Thyroid Association guidelines changed, lobectomy rates increased significantly without a concomitant increase in the completion of thyroidectomy.

[Application status and progress of intraoperative nerve monitoring in pelvic autonomic nerve preserving radical resection of rectal cancer].

The current treatment strategy for rectal cancer is a comprehensive treatment centered on surgery. The application of total mesorectal excision (TME) has significantly reduced the local recurrence rate and improved the survival prognosis, but a series of pelvic organ dysfunction caused by pelvic autonomic nerve injury during the operation will reduce the postoperative quality of life of patients. Pelvic autonomic nerve preserving (PANP) radical proctectomy has emerged, but the biggest challenge in the implementation process of this technology is the accurate identification of nerves. A series of studies have shown that pelvic intraoperative autonomic monitoring (pIONM) can effectively assist surgeons to identify nerves, The purpose of this article is to introduce the function of pelvic autonomic nerve, the clinical manifestation of postoperative pelvic dysfunction and its relationship with nerve injury, the key points of implementing PANP, and the current situation and research progress of pIONM technology application.

[Changes of uterine morphology and endometrial T2 signal intensity in the fibrotic repair secondary to endometrial injury].

Objective: To investigate the value of uterine morphological parameters and endometrial T2 signal intensity (T2-SI) in evaluating the degree of the fibrotic repair secondary to endometrial injury. Methods: From Sep. 2018 to Feb. 2023, this study prospectively enrolled 29 patients with fibrotic repair secondary to severe endometrial injury (severe group), 17 patients with fibrotic repair secondary to mild to moderate endometrial injury (mild to moderate group), and 40 healthy women of reproductive age (control group) in Nanjing Drum Tower Hospital. The length of uterine cavity (LUC), length of cervix and isthmus (LCI), width of upper uterine cavity (WUUC) and width of lower uterine cavity (WLUC) were measured using magnetic resonance imaging. T2-SI of endometrium and subcutaneous fat of buttocks were measured, and endometrial normalized T2-SI (nT2-SI; T2-SI of endometrium/T2-SI of subcutaneous fat of buttocks) was calculated. Statistical analyses of data were performed using one-way analysis of variance, Mann-Whitney U test, intraclass correlation coefficient, Spearman rho test, area under the receiver operating characteristic curve (AUC). Results: LUC, WUUC, WLUC and endometrial nT2-SI of severe group [(19.7±3.5) mm, (26.9±6.4) mm, (7.9±1.4) mm, 0.73±0.11, respectively] were significantly lower than those of the control group (all P<0.01), while LCI and WUUC/LUC [(51.3±7.3) mm and 1.38±0.34] were significantly higher than those of the control group (all P<0.001). LUC and WLUC of severe group were significantly lower than those of mild to moderate group [(32.4±5.1) mm and (8.8±1.2) mm; all P<0.05], while LCI and WUUC/LUC were significantly higher than those of mild to moderate group [(41.8±8.6) mm and 0.94±0.16; all P<0.001]. LUC and endometrial nT2-SI of mild to moderate group were significantly lower than those of the control group [ (32.4±5.1) vs (35.3±3.5) mm, 0.68±0.13 vs 0.80±0.12; all P<0.01]. LUC, WUUC, WLUC and endometrial nT2-SI were significantly negatively correlated to the degree of the fibrotic repair secondary to endometrial injury (Spearman rho:-0.794, -0.441, -0.471 and -0.316, respectively; all P<0.05), while LCI and WUUC/LUC were significantly positively correlated to the degree of the fibrotic repair secondary to endometrial injury (Spearman rho: 0.481 and 0.674, respectively; all P<0.05). LUC and WUUC/LUC showed high value in distinguishing severe group from the control group or mild to moderate group (all AUC>0.9, all P<0.001). Conclusion: As noninvasive and quantitative biomarkers, uterine morphological parameters and endometrial nT2-SI could evaluate the degree of the fibrotic repair secondary to endometrial injury.

Research progress into adipose tissue macrophages and insulin resistance.

In recent years, there has been an increasing incidence of metabolic syndrome, type 2 diabetes, and cardiovascular events related to insulin resistance. As one of the target organs for insulin, adipose tissue is essential for maintaining in vivo immune homeostasis and metabolic regulation. Currently, the specific adipose tissue mechanisms involved in insulin resistance remain incompletely understood. There is increasing evidence that the process of insulin resistance is mostly accompanied by a dramatic increase in the number and phenotypic changes of adipose tissue macrophages (ATMs). In this review, we discuss the origins and functions of ATMs, some regulatory factors of ATM phenotypes, and the mechanisms through which ATMs mediate insulin resistance. We explore how ATM phenotypes contribute to insulin resistance in adipose tissue. We expect that modulation of ATM phenotypes will provide a novel strategy for the treatment of diseases associated with insulin resistance.

Choice in Ablative Therapies for Thyroid Nodules.

Ultrasound-guided ablation procedures have been growing in popularity and offer many advantages compared with traditional surgery for thyroid nodules. Many technologies are available, with thermal ablative techniques being the most popular currently though other nonthermal techniques, such as cryoablation and electroporation, are gaining interest. The objective of the present review is to provide an overview of each of the currently available ablative therapies and their applications in various clinical indications.

[Effect of miR-96-5p targeting IRS1 on apoptosis of PC12 cells induced by aluminum maltol].

Objective: To investigate the effect and mechanism of miR-96-5p on apoptosis of PC12 cells induced by maltol aluminum. Methods: In January 2021, PC12 cells at logarithmic growth phase were divided into blank control group and low, medium and high dose group. Cells in each group were treated with 0, 100, 200 and 400 µmol/L maltol aluminum for 24 hours respectively. Cells were collected and cell apoptosis rates were detected by flow cytometry, miR-96-5p and insulin receptor substrate 1 (IRS1) mRNA expressions were detected by qRT-PCR, and the protein expression levels of cysteine protease 3 (Caspase3) 、activated cysteine protease 3 (Cleaved-caspase3) 、IRS1、phosphorylated protein kinase B (p-AKT) and phosphorylated glucose synthesis kinase 3ß (p-GSK3ß) were detected by western blotting. The target binding relationship between miR-96-5p and IRS1 was detected by double luciferase reporter gene experiment. The miR-96-5p inhibitor cells and negative control cells were constructed after transfecting PC12 cells with miR-96-5p inhibitor for 24 hours. The cells were divided into blank control group, negative control group, aluminum exposure group, aluminum exposure+negative control group, aluminum exposure+miR-96-5p inhibition group, and miR-96-5p inhibition group. After transfecting PC12 cells with miR-96-5p inhibition and IRS1 siRNA for 24 h, the cells were divided into aluminum exposure+miR-96-5p inhibition+negative control group and aluminum exposure+miR-96-5p inhibition+IRS1 inhibition group. The control group was cultured in complete culture medium, and cells in the aluminum exposure group were treated with 200 µmol/L maltol aluminum for 24 hours. Cells in each group were collected and the apoptosis rate, miR-96-5p and IRS1 mRNA expression levels, as well as protein expression levels of Caspase3, Cleaved-caspase3, IRS1, p-AKT, and p-GSK3ß were measured. Results: After 24 hours of exposure, compared with blank control group and low-dose group, the apoptosis rates, relative expressions of Caspase3 and Cleaved-caspase3 proteins, and relative expressions of miR-96-5p in the medium and high-dose groups of PC12 cells were significantly increased, while the relative expression levels of IRS1 mRNA, IRS1, p-AKT and p-GSK3ß proteins were significantly decreased (P<0.05). Targetscan prediction and double luciferase report experiment both proved that IRS1 was a direct target gene of miR-96-5p. In the transfection experiment, compared with the aluminum exposure group, the apoptosis rate, the relative expressions of Caspase3 and Cleaved-caspase3 proteins, the relative expression of miR-96-5p in the aluminum exposure+miR-96-5p inhibition group were significantly decreased, while the relative expression levels of IRS1 mRNA and IRS1, p-AKT and p-GSK3ß proteins were significantly increased (P<0.05). In the IRS1 low expression experiment, compared with the aluminum exposure+miR-96-5p inhibition+negative control group, the apoptosis rate, the relative expressions of Caspase3 and Cleaved-caspase3 proteins in the aluminum exposure+miR-96-5p inhibition+IRS1 inhibition group were significantly increased, while the relative expression levels of IRS1 mRNA and IRS1, p-AKT and p-GSK3ß proteins were significantly decreased (P<0.05) . Conclusion: The increased expression of miR-96-5p and the targeted inhibition of IRS1 may be one of the mechanisms of apoptosis of PC12 cells induced by maltol aluminum exposure.

Acceleration of bone repair in critical-size defect using angiopoietin-2 associated with novel carbon nanotubes scaffold via mitophagy-pyroptosis pathway.

OBJECTIVE: To investigate the curative effect of Ang-2 combined with novel carbon nanotubes (CNTs) scaffold critical-size bone defect in rabbits. MATERIALS AND METHODS: CNTs with good properties were first prepared by freeze-drying method. The mechanical properties and surface hydrophilicity of scaffolds were improved by adjusting the addition ratio of polylactic acid (LPA) and chitin fibers (CHI). After purification and functionalization of CNTs, CNTs/PLA/CHI three-dimensional porous scaffolds were prepared for animal experiments. Subsequently, the CNTs/PLA/CHI scaffolds were implanted into the rabbit critical-sized radius defect model to evaluate the osteogenic properties in vivo. Adult male New Zealand white rabbits were randomly allocated into three groups. Group A was the control group, and both groups B and C underwent radial bone defect surgery and implanted CNTs/PLA/CHI scaffolds. Animals in group C received a daily local injection of 1 mL of 400 ng/mL Ang-2 dissolved in physiological saline in the bone defect area for up to 14 days after surgery, while group B received the same amount of physiological saline. RESULTS: Scanning electron microscope results showed that the porosity of the CNTs/PLA/CHI three-dimensional porous scaffolds was as high as 80%. The surface contact angle was 35° to 55°, and the hydrophilicity was suitable for cell adhesion and growth. The CNTs/PLA/CHI three-dimensional porous scaffolds had excellent biological properties. The general observation and X-ray imaging after 12 weeks together indicated that the CNTs/PLA/CHI scaffolds could accelerate bone repair with the combination of endogenous angiogenic factor Ang-2. The results of western blotting and histology revealed that the expression of mitophagy proteins LC3, Beclin-1, PINK1 and Parkin was elevated in the new bone, and the expression of pyroptosis proteins Nod-like receptor protein NLRP3, caspase-1 and Gasdermin D (GSDMD) was decreased. CONCLUSIONS: Ang-2 associated with CNTs/PLA/CHI scaffolds accelerated bone regeneration through autophagy-pyroptosis pathway.

[Centromere protein U is highly expressed in colorectal cancer and associated with a poor long-term prognosis].

OBJECTIVE: To analyze the expression of centromere protein U (CENPU) in colorectal cancer and its predictive value for long-term prognosis of the patients. METHODS: We retrospectively analyzed the data of 102 patients with colorectal cancer undergoing radical resection in our hospital between January, 2005 and December, 2011. The expression level of CENPU in colorectal cancer tissue was detected immunohistochemically, and its association with clinicopathological characteristics of the patients were analyzed. The patients were divided into low expression group (n=51) and high expression group (n=51) based on the median CENPU expression level for analysis the value of CENPU for predicting long-term prognosis of the patients after radical resection of the tumors. In the in vitro study, we constructed colorectal cancer cell lines with CENPU interference and CENPU overexpression by lentiviral transfection and assessed the changes in the proliferation, migration and invasion of the cells using CCK-8 assay and Transwell assay. RESULTS: The protein expression level of CENPU was significantly higher in colorectal cancer tissues than in the adjacent tissues (P < 0.05) and was positively correlated with the expressions levels of Ki67 (r=0.569, P < 0.05) and VEGF-C (r=0.629, P < 0.05). CENPU expression level in colorectal cancer tissue was closely related with tumor progression and clinicopathological stage of the tumor (P < 0.05). Kaplan-Meier survival analysis showed that the patients with high CENPU expression had significantly decreased postoperative overall survival (χ2=11.155, P < 0.05); Cox multivariate regression analysis suggested that CENPU expression level was an independent risk factor affecting the overall survival of the patients after radical resection (HR=1.848, P < 0.05). The results of cell experiments demonstrated that high CENPU expression significantly promoted the proliferation, migration and invasion of the tumor cells. CONCLUSION: CENPU is highly expressed in colorectal cancer tissues in closely correlation with tumor progression and may serve as a potential biomarker for evaluating the long-term prognosis of colorectal cancer patients.

Are Kids More Than Just Little Adults? A Comparison of Surgical Outcomes.

INTRODUCTION: While complication rates have been well described using the National Surgical Quality Improvement Program (NSQIP) and National Surgical Quality Improvement Program-Pediatric registries, there have been no direct comparisons of outcomes between adults and children. Our objective was to describe differences in postoperative outcomes between children and adults undergoing common surgical procedures. METHODS: Using data from 2013 to 2017, we identified patients undergoing laparoscopic appendectomy, laparoscopic cholecystectomy, thyroidectomy, and colectomy. Propensity score matching on gender, race, American Society of Anesthesiologists class, surgical indication, and procedure type was performed. Outcomes included surgical site infection (SSI), readmission rates, mortality/serious morbidity, and hospital length of stay and were analyzed using χ2 and student's t-test with statistical significance defined as P < 0.05. RESULTS: We matched 79,866 patients from 812 hospitals. Compared to adults, children had higher rates of SSI following appendectomy (4.12% versus 1.40%, P < 0.01) and cholecystectomy (0.96% versus 0.66%, P = 0.04), readmission following appendectomy (4.26% versus 2.47%, P < 0.01), and longer length of stay in all procedures. In adults, 30-day mortality/serious morbidity was higher for all procedures. CONCLUSIONS: Compared to adults, children demonstrate unique surgical complication and outcome profiles. Quality improvement efforts such as SSI prevention bundles and enhanced recovery protocols used in adults should be expanded to children.

Efficacy of robot-assisted core decompression combined with human umbilical cord-derived mesenchymal stem cell transplantation for osteonecrosis of the femoral head.

OBJECTIVE: The aim of this paper was to evaluate the effects of robot-assisted core decompression combined with human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation for early-stage osteonecrosis of the femoral head (ONFH). PATIENTS AND METHODS: A retrospective analysis was performed on 18 patients with a total of 26 hips who were diagnosed with Association Research Circulation Osseous stage 2 avascular necrosis of the femoral head and who received core decompression combined with hUC-MSC transplantation. All surgeries were completed under robotic assistance. Preoperative and postoperative visual analogue scale (VAS) scores and the Harris Hip Score (HHS) were recorded to assess clinical function. A Magnetic Resonance Imaging (MRI) examination was performed at the last follow-up. RESULTS: The mean follow-up was 18.6 months (12-28 months), the VAS score (4.5±0.8 vs. 0.9±0.2, t=12.6, p≤0.001) and HHS (79.5±5.8 vs. 60.5±4.6, t=14.3, p≤0.001) were significantly improved at the last follow-up, compared with preoperative value. The MRI results showed that the necrotic volume of the femoral heads was significantly reduced. CONCLUSIONS: Robot-assisted core decompression combined with hUC-MSC transplantation is a feasible and relatively safe method for the treatment of femoral head necrosis.

Cost analysis of reflexive versus selective molecular testing for indeterminate thyroid nodules.

BACKGROUND: Molecular testing is now commonly used to refine the diagnosis of indeterminate thyroid nodules. The purpose of this study is to compare the costs of a reflexive molecular testing strategy to a selective testing strategy for indeterminate thyroid nodules. METHODS: A Markov model was constructed to estimate the annual cost of diagnosis and treatment of a real-world cohort of patients with cytologically indeterminate thyroid nodules, comparing a reflexive testing strategy to a selective testing strategy. Model variables were abstracted from institutional clinical trial data, literature review, and the Medicare physician fee schedule. RESULTS: The average cost per patient in the reflexive testing strategy was $8,045, compared with $6,090 in the selective testing strategy. In 10,000 Monte Carlo simulations, diagnostic thyroid lobectomy for benign nodules was performed in 2,440 patients in the reflexive testing arm, compared with 3,389 patients in the selective testing arm, and unintentional observation for malignant nodules occurred in 479 patients in the reflexive testing arm, compared with 772 patients in the selective testing arm. The cost of molecular testing had the greatest impact on overall costs, with $1,050 representing the cost below which the reflexive testing strategy was cost saving compared with the selective testing strategy. CONCLUSION: In this cost-modeling study, reflexive molecular testing for indeterminate thyroid nodules enabled patients to avoid unnecessary thyroid lobectomy at an estimated cost of $20,600 per surgery avoided.

[Analysis of components of proteins from Echinococcus granulosus cyst fluid].

OBJECTIVE: To analyze the components of proteins from Echinococcus granulosus cyst fluid using the shotgun method, and to identify the active components with potential regulatory effects for immune dysregulation diseases. METHODS: The E. granulosus cyst fluid was collected aseptically from the hepatic cysts of patients with cystic echinococcosis, and characterized by liquid chromatography (LC) tandem mass spectrometry (MS/MS) following digestion with trypsin. The protein data were searched using the software MaxQuant version 1.6.1.0 and the cellular components, molecular functions, and biological processes of the identified proteins were analyzed using the Gene Ontology (GO) method. RESULTS: The E. granulosus cyst fluid separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) had a relative molecular mass of 25 to 70 kDa. LS-MS/MS analysis identified 37 proteins, including 32 known proteins and 5 unknown proteins. At least 4 proteins were preliminarily found to exhibit potential regulatory effects for immune dysregulation diseases, including antigen B, glutathione-S-transferase (GST), thioredoxin peroxidase (TPX) and malate dehydrogenase (MDH). GO enrichment analysis showed that the identified proteins had 149 molecular functions and were involved in 341 biological processes. CONCLUSIONS: E. granulosus cyst fluid has a variety of protein components, and four known proteins are preliminarily identified to be associated with immune dysregulation diseases.

[HBx promotes ubiquitination and degradation of ZO1 and increases the migration and invasion of liver cancer cells].

Objective: To study the effect of hepatitis B virus X protein (HBx) expression level on migration and invasion of zonula occludens protein-1 (ZO-1) in HepG2 liver cancer cells. Methods: Liver cancer cells were transfected with HBV full gene plasmid (pcDNA3.1-HBV1. 1 or pcDNA3.1-HBV1.3), empty plasmid (pcDNA3.1) and HBV-encoded protein plasmids (pHBc, pHBs, pHBp and pHBx), respectively. Western blot and RT-PCR were used to detect ZO1 protein and mRNA levels. Immunoprecipitation was used to detect transfected pHBx. Western blot was used to detect ZO1 ubiquitination levels. Transwell chambers were used to assess cell migration and invasion. Cell proliferation and lactate dehydrogenase assay was used to detect siRNA transfecting targeting ZO1. Flow cytometry was used to detect cell apoptosis and cycle. The data was compared between two and multiple groups by using an independent sample t-test and one-way analysis of variance. Results: Compared with the empty plasmid, ZO1 protein level in HepG2 cells after transiently transfected with pHBV1.1 and pHBV1.3 was decreased by 42.99% ± 6.8% and 55.0% 5 ± 4.56%, respectively, and their mRNA levels did not change significantly. ZO1 protein level in Huh7 cells was decreased by 17.46% ± 4.94% and 47.53% ± 3.38%, respectively. ZO1 protein level after transfection with pHBx was decreased by 47.02% ± 3.4%, while the ZO1 protein level after transfection with pHBc, pHBs and pHBp did not change significantly. ZO1 mRNA level was unaffected with pHBx transfection. ZO1 ubiquitin level and cell migration and invasion ability in HepG2 cells was significantly increased with transfected pHBx. HepG2 cells proliferation, apoptosis and cycle after transfection with ZO1-targeted siRNA did not change significantly, but the migration and invasion ability were significantly increased. Conclusion: HBx can increase the migration and invasion of liver cancer cells by promoting the ubiquitination and degradation of ZO1 protein level.