Patient­reported outcome measures for assessing health­related quality of life in patients with differentiated thyroid cancer: a systematic review.

BACKGROUND: Patient-reported outcome measures (PROMs) have become important tools for evaluating health-related quality of life (HRQOL) in patients with differentiated thyroid cancer (DTC). While there are many PROMs available to measure HRQOL, there is a lack of a comprehensive overview of these PROMs. Therefore, we aimed to systematically review and categorize all PROMs that have been used to measure HRQOL in patients with DTC. MATERIALS AND METHODS: After determining the search strategy and identifying inclusion and exclusion criteria, articles were searched in PubMed and EMBASE from January 1900 to September 2023. Information on PROMs from the included studies, such as development language, target population, (sub)scales name, number of items per (sub)scale, completion time, and validation, was extracted and synthesized. The frequency with which PROMs were utilized in the included studies was also graphed. After innovatively classifying PROMs as five categories, all of the included PROMs were allocated to their respective categories. RESULTS: A total of 330 articles fulfilled all of the criteria, and they utilized 96 different PROMs to measure HRQOL in DTC patients. The 96 PROMs were classified into five categories, namely universal PROMs (16/96), DTC-related PROMs (11/96), radioiodine-related PROMs (4/96), operation-related PROMs (37/96), and psychology-related PROMs (28/96). Among them, some PROMs were the frequently employed PROMs to assess diverse aspects of HRQOL in patients with DTC. CONCLUSION: A large number of PROMs are available for patients with DTC, which evaluate all aspects of HRQOL. Combining the relevant information and frequency of PROMs utilization, it can provide convenience and reference for researchers to select PROMs across different categories. However, a more detailed critical appraisal of the PROMs used in various clinical scenarios is required. Additionally, PROMs usage frequency in previous studies can indirectly indicate the comprehensiveness or gaps in HRQOL aspects studied, guiding further review or research.

Long-term follow-up and prognostic analysis of parotid tumors in children and adolescents.

Objectives: The objective of this study is to summarize the clinical characteristics, treatment, and prognosis of parotid tumors in children and adolescents. Methods: Fifty-three children and adolescents diagnosed with parotid gland tumors were included. Survival was evaluated using the Kaplan-Meier method. Log-rank test and multivariate analysis were used to analyze the association between clinical factors and recurrence. Results: Of the 53 patients, 30 cases were benign and 23 cases were malignant. All patients underwent surgery. Patients with malignant tumors with high-risk factors received radiotherapy or chemotherapy. The median follow-up time was 61 months. Of these, 1 patient with benign tumor and 5 patients with malignant tumors recurred. Of the patients with malignant tumors, 2 developed distant metastases and 2 died. The 5-year overall survival (OS) and 5-year locoregional recurrence-free survival (LRFS) rates for benign tumors were 100.0% and 92.9%, respectively, whereas the 5-year OS and 5-year LRFS rates for malignant tumors were 94.4% and 72.5%, respectively. The log-rank univariate test showed that tumor size >3.5 cm (p = .056), distant metastasis (p = .056), and stage III and IV (p = .032) were associated with recurrence. However, multivariate analysis did not show the above factors to be independent prognostic factors for LRFS. Conclusion: Surgery for benign tumors depends on the location and size. Surgery for malignant parotid tumors depends mainly on the stage, grade, pathological type, and recurrence. Prophylactic lymph node dissection is required for high-grade tumors. Radiotherapy or chemotherapy for children needs more research. Both benign and malignant tumors have high survival rates after active treatment. Level of evidence: Level 2.

An analysis of health-related quality of life in children and adolescents after parotidectomy based on patient-reported outcomes.

PURPOSE: To assess health-related quality of life (HRQoL) and its influencing factors in these pediatric patients undergoing parotidectomy. METHODS: This was a cross-sectional study that included 37 children and adolescents (≤ 19 years) with parotid gland tumors who were treated in Sichuan Cancer Hospital between January 2006 and November 2021. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30). The Wilcoxon rank sum test was used to analyze the factors influencing patients' HRQoL. RESULTS: 37 children and adolescents were included in the study, including 22 cases of benign tumors and 15 cases of malignant tumors. All patients underwent surgery, and some patients with malignant tumors received radiotherapy or chemotherapy. Malignancy, permanent facial palsy, and Frey syndrome were associated with worse HRQoL in children and adolescents with parotid gland tumors. Radiotherapy and no cervical lymph node dissection were associated with worse HRQoL in pediatric patients with malignancy. The surgical approach of parotid is not a factor influencing HRQoL. CONCLUSION: Factors associated with HRQoL in children and adolescents with parotid gland tumors include pathological types, permanent facial palsy, and Frey syndrome. In addition, factors affecting patients with malignancy include lateral lymph node dissection and radiotherapy.

The updated surgical steps of gasless transaxillary endoscopic thyroidectomy with neck level and region orientation for thyroid cancer.

Introduction: We previously made a detailed expansion to the gasless transaxillary endoscopic thyroidectomy(GTET) procedure described in the previous literatures. In this study, we optimized the procedure focused on the limitation of the approach in terms of trauma and lymph node dissection and made a comparison with the early procedure. Materials and methods: This paper gave a detailed description of the updated procedure and prospectively collected data about patients with papillary thyroid carcinoma(PTC) performed by the two procedures from December 2020 to April 2023. The differences in surgical outcome, surgical trauma and parathyroid gland(PG) function protection were analyzed. Results: Of the 302 patients, 184 underwent with early procedure(EP), and 118 underwent with updated procedure(UP). The surgical outcomes of operative time, time of thyroidectomy and central neck dissection, blood loss, drainage and postoperative hospital stay were shorter in UP than that of the EP. The mean number of lymph nodes retrieved and weight of dissection lymphatic tissue in the UP were significantly more than that in EP without increasing the mean number of metastatic lymph nodes. Postoperative complications did not differ between the two procedures. The UP had more advantages in the identification and preservation of the superior parathyroid gland, however, it did not improve the preservation in situ of the inferior parathyroid gland. The visual analog scale score for pain and the changes among inflammation factors was lower in the UP. Conclusion: The UP of GTET could perform safely and efficiently while reducing surgical trauma in selected patients.

Construction of a system for head and neck tumor traceless resection with non-inflatable transaxillary total endoscopic surgery.

Radical cure and functional preservation of tumors are the fundamental goals of surgical treatment of head and neck tumors, and the preservation of good aesthetics is a higher pursuit on this basis. Fully hiding the surgical incision and reducing the visibility of scars are important goals of cosmetic surgery. Using complete endoscopy for the head and neck is an effective method. CO2-free transaxillary total endoscopic surgery is a method with many advantages, which has been widely used in the resection of thyroid tumors, but for other parts and types of tumors in the head and neck, this surgical method is rarely used. The research team expanded its application scope and applied it to submandibular gland tumor resection and other head and neck surgeries for the first time. Through this exploration, it improved traction devices such as retractors, strictly limited the surgical indications, analyzed and summarized the key points, steps and methods of surgery, and built a treatment system for head and neck tumor surgery under complete endoscopy using the non-inflatable transaxillary approach. In this article, we introduce the system and select typical cases to share.

circ_0000045 promotes proliferation, migration, and invasion of head and neck squamous cell carcinomas via regulating HSP70 and MAPK pathway.

OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) is one severe malignancy driven by complex cellular and signaling mechanisms. However, the roles of circular RNAs (circRNAs) in HNSCC's development remains poorly understood. Therefore, this study investigated the functions of differentially expressed circRNAs in regulating HNSCC cell functions. METHODS: Differentially expressed circRNAs were characterized through RNA sequencing in HNSCC tissues. CircRNA's identity was then confirmed using RT-PCR and Sanger's sequencing. Next, expression levels of circRNA and mRNA were detected by qRT-PCR, after which protein abundances were measured by Western blotting. Subsequently, the proliferation, migration, and invasion of HNSCC cells was assessed by MTS, wound healing, and Transwell system, respectively, followed by identification of circRNA-binding proteins in HNSCC cells by circRNA pull-down, coupled with mass spectrometry. RESULTS: Great alterations in circRNA profiles were detected in HNSCC tissues, including the elevated expression of circ_0000045. As observed, silencing of circ_0000045 effectively repressed the proliferation, migration, and invasion of HNSCC cell lines (FaDu and SCC-9). Contrarily, circ_0000045's overexpression promoted the proliferation, migration, and invasion in FaDu and SCC-9 cells. Results also showed that circ_0000045 was associated with multiple RNA-binding proteins in HNSCC cells, such as HSP70. Moreover, circ_0000045 knockdown enhanced HSP70 expression and inhibited JNK2 and P38's expression in HNSCC cells, which were oppositely regulated by circ_0000045's overexpression. CONCLUSION: The high expression of circ_0000045; therefore, promoted cell proliferation, migration, and invasion during HNSCC's development through regulating HSP70 protein and mitogen-activated protein kinase signaling.

Digital surgery group versus traditional experience group in head and neck reconstruction: a retrospective controlled study to analyze clinical value and time-economic-social effect.

OBJECTIVE: Discuss the application value of digital surgical technology in the reconstruction of head and neck defects after tumor resection and comprehensively evaluate time-economic-benefit cost. METHODS: A retrospective analysis of head and neck cancer patients who underwent reconstructive operations in head and neck surgery at Sichuan Cancer Hospital from January 2015 to January 2021 was performed. According to the inclusion and exclusion criteria, a total of 52 cases were included, including 25 cases using digital surgery (DS) and 27 cases using the conventional surgery (CS). The clinical-pathological characteristics, postoperative complications, functional aesthetic evaluation indexes, and time-cost-satisfaction evaluation indexes between the two groups were compared and statistically analyzed. Typical cases using digital surgery were shared. RESULTS: Outcomes between the two groups were comparable, and there was no significant difference in survival outcome and follow-up time between the two groups (P > 0.05). There was no significant difference between the two groups in the defect size, pathological type, other major clinicopathological features, or operation-related indicators (P > 0.05). The incidence of titanium plate displacement, deformation or exposure, and facial scar deformity in the DS group was significantly lower than that in the CS group (P < 0.05). However, there was no significant difference in other short-term or long-term complications (P > 0.05). The incidence of dysphagia and eating disorders in the DS group was significantly reduced (P < 0.05). The speech and social functions were improved, but not significantly (P > 0.05). Meanwhile, there was no significant difference in the evaluation index of facial aesthetics in this study (P > 0.05). Furthermore, the total operation time, preparation time of bone flap from the donor site, osteotomy time, and reconstruction time in the DS group were significantly lower than those in the traditional operation group (P < 0.05), but the shaping time and vascular anastomosis time of recipient area could not be shortened (P > 0.05). In addition, there was no significant difference in total hospitalization days between the DS group and CS group (P > 0.05), but the time of ICU treatment and postoperative intravenous nutrition support in the DS group were shorter than those in the CS group (P < 0.05). In particular, the preoperative doctor-patient communication of the DS group was more effective, and the treatment satisfaction of patients including their families was higher after operation (P < 0.05). CONCLUSION: Comprehensive application of digital surgical technology (CAD, CAM, VR, MA, etc.) in the reconstruction of the head and neck after tumor resection is feasible in clinical practice, which can not only improve the accuracy of repair, decrease some surgical complications, better preserve and improve patient's diet and speech function, and reduce the operation and hospitalization time, but also increase the treatment cost. Furthermore, it is conducive to doctor-patient communication and improves patient satisfaction.

Gasless transaxillary endoscopic thyroidectomy for unilateral low-risk thyroid cancer: Li's six-step method.

The past decade has witnessed rapid advances in gasless transaxillary endoscopic thyroidectomy (GTET) for thyroid cancer, which has become a reliable procedure with good therapeutic effectiveness, aesthetic benefits, and safety. This procedure has been widely promoted in some Asian countries; however, few studies have described the specific surgical steps for unilateral low-risk thyroid cancer. Based on a review of the literature and our own clinical experience, we introduce in detail the surgical procedure of GTET for the unilateral low-risk thyroid cancer, briefly summarized into Li's 6 steps: surgical position and incision design; creation of surgical cavities; dissection of the superior pole of the thyroid and its vessels, and identification and protection of superior laryngeal nerve; identification and protection of the superior parathyroid gland, and identification of the inferior parathyroid gland; identification and protection of the recurrent laryngeal nerve and the inferior parathyroid gland, and central neck dissection; and processing of the suspensory ligaments of thyroid gland and en bloc resection of the tumor. The six-step approach is simple to learn. The lymph nodes are dissected first, followed by resection of the primary lesion and protect important structures, which meets the principles of radical tumor treatment. It is hoped that the proposed Li's six-step method can promote the standardized, safe, and wide application in treating early thyroid cancer.

The application of venous nerve conduit trap in the immediate repair and reconstruction of facial nerve in parotid gland tumor: an attempt of a new technique.

OBJECTIVE: To introduce the application of venous nerve conduit in the immediate repair and reconstruction of facial nerve in parotid gland tumor. METHODS: Three patients with parotid gland tumor in Sichuan Provincial Cancer Hospital were reviewed. All patients were found that the tumor encased and invaded the facial nerve which was difficult to be separated during the operation when all patients were treated with facial nerve repair and reconstruction with the venous nerve conduit trapping technique. RESULTS: After 1-year follow-up, all patients recovered well in facial nerve function. CONCLUSION: The venous nerve conduit trapping technique is an effective attempt in the immediate repair and reconstruction of facial nerve in parotid gland tumor, but it needs to be further confirmed by multiple studies.

Relationship between the extent of central node dissection and parathyroid function preservation in thyroid cancer surgery.

BACKGROUND: The risk and effect of hypocalcemia following surgery of different magnitudes remains unclear. Thus, we assessed whether different extents of central lymph node dissection (CLND) and status of preserved parathyroid glands can influence parathyroid function in differentiated thyroid carcinoma (DTC) patients with initial surgical resection. METHODS: Participants were categorized into 6 groups based on the extent of the surgical procedures, number of parathyroid glands preserved in situ, and parathyroid autotransplantation. The frequencies of hypocalcemia, serum calcium (Ca) levels, and parathyroid hormone (PTH) levels among the different groups were analyzed. RESULTS: The prevalence of hypocalcemia, number and status of parathyroid glands preserved in situ, and parathyroid autotransplantation were inversely related to extensive CLND (r=-0.18; P<0.05). The decrease of serum Ca and PTH was most severe on postoperative days (POD) 1-7. The incidence of hypocalcemia was higher in Group C than in Group B and A (P<0.05). The average postoperative serum Ca and PTH levels in Group C were significantly lower than group A on POD 1-7 (P<0.05). The incidence of hypocalcemia was obviously increased in Group D compared to Groups E and F (P<0.05). The mean serum Ca and PTH levels in Group D were significantly lower than in Group F (P<0.05), and the same results could be observed between Groups D and E (P<0.05). However, through parathyroid autotransplantation, there was no significant difference that could be found between Groups E and F on POD 1-7 (P>0.05). CONCLUSIONS: With the expansion of CLND scope, postoperative parathyroid function will be affected, increasing the risk of postoperative hypocalcemia. When at least 1-2 parathyroid glands were reserved in situ plus at least 1 parathyroid gland autotransplantation, there was little effect on postoperative parathyroid function.

Retracted: Parthenolide Inhibits the Proliferation of MDA-T32 Papillary Thyroid Carcinoma Cells In Vitro and in Mouse Tumor Xenografts and Activates Autophagy and Apoptosis by Downregulation of the Mammalian Target of Rapamycin (mTOR)/PI3K/AKT Signaling Pathway.

This paper is being retracted at the author's request. Reference: 1. Chao Li, Yuqiu Zhou, Yongcong Cai, Chunyan Shui, Wei Liu, Xu Wang, Jian Jiang, Dingfen Zeng, Chunhan Gui, Ronghao Sun: Parthenolide Inhibits the Proliferation of MDA-T32 Papillary Thyroid Carcinoma Cells In Vitro and in Mouse Tumor Xenografts and Activates Autophagy and Apoptosis by Downregulation of the Mammalian Target of Rapamycin (mTOR)/PI3K/AKT Signaling Pathway. Med Sci Monit, 2019; 25: 5054-5061. DOI: 10.12659/MSM.915387.

An algorithm for one-stage malignant oncologic scalp reconstruction.

BACKGROUND: Scalp reconstruction has always been a challenging problem after oncological resection. Advanced surgical techniques can reconstruct any defects, but there are a large number of patients who cannot benefit from surgery for immature strategies. The authors here describe an algorithm for selecting the best reconstructive categories and minimizing complications according to the surgical defect of scalp tumors. METHODS: A single-institution retrospective review was conducted that included 173 patients with scalp tumors treated with surgery followed by reconstruction. Patients were identified by tumor type and nature; the location of scalp defect, size, and depth; the types of reconstructions and surgical. A systematic algorithm was developed according to our findings and current literature. RESULTS: Small defects (≤4 cm2) could be closed by primary closure. Medium defects (4-30 cm2) were reconstructed by local flaps. We routinely used skin graft for significant surgical defects (30-90 cm2). And the tumor's location did not have an impact on reconstructive categories of above three types of defects. Free flaps should reconstruct very large-sized defects (>90 cm2) in frontal, temporal, and vertex locations while pedicle flaps suited for occipital defects due to its anatomic vicinity. The reconstruction algorithm of recurrent disease was like the management in primary tumors except for the medium size defect in the occipital region that was primarily reconstructed by a skin graft. Multiple free flaps reconstruction is the best possibility for total scalp resection. Free flap reconstruction is used mainly for composite resection of the scalp, calvarium, and dura. CONCLUSIONS: Successful scalp reconstruction requires careful preoperative assessment, flexible and precisely intraoperative management. The algorithm based on defect size, depth, and location can supply some degree of guidelines when considering choosing suitable reconstructive procedures.

Surgery for retrosternal goiter: cervical approach.

BACKGROUND: Retrosternal goiter refers to when the thyroid gland extends from the neck to the substernal portion, descending below the thoracic inlet into the mediastinum. It is typically accompanied by compressive symptoms, and most patients need to undergo surgery. This retrospective study set out to analyze the surgical approach to retrosternal goiter and to evaluate perioperative complications, with the aim of recommending best surgical technique. METHODS: We carried out retrospective analysis of 115 patients with retrosternal goiter treated at our center between May 4, 2011 and March 19, 2019. We analyzed patient characteristics, surgical methods, and perioperative complications using SPSS. RESULTS: Of the 115 patients in our study, 112 underwent thyroidectomy by cervical approach, with only 3 requiring an extracervical approach. The median age of the patients was 52.3 years, and the majority were female (81.74%). Most of the patients (73.91%) experienced no symptoms but were diagnosed with tracheal compression during surgery or preoperative imaging examination. Ninety-eight (85.22%) of our patients underwent preoperative evaluation of their condition by CT imaging. No obvious surgical contraindications were found before thyroid function tests. The mean operation time was 115.11 min, and the average amount of bleeding during surgery was 54.43 mL. The mean postoperative hospital stay was 5.38 days. In 109 cases (94.78%), the goiter was found to be benign, and malignancy was diagnosed in 6 patients (5.22%). Of the 112 patients who were treated with the cervical approach, 7 (6.25%) experienced recurrent laryngeal nerve palsy; 6 of these cases were transitory and 1 was permanent. The number of patients treated by cervical and extracervical approach who experienced transient hypocalcaemia was 23 (20.54%) and 2, respectively. Transient hypoparathyroidism affected 16 patients (14.29%) treated by cervical approach. Two patients had tracheomalacia phenomenon and one patient had pleural effusion after surgery. No cases experienced permanent hypocalcemia, permanent hypoparathyroidism, postoperative hematoma, tracheostomy, or death. CONCLUSIONS: Retrosternal goiter surgery is challenging for surgeons. The best surgical approach for the patient should be based on CT scan evaluation. In our study, based on preoperative CT imaging and in-operation evaluation, 50% of the tumor volume was located below the thoracic inlet and 50% of the tumor volume was located above the thoracic inlet in almost all of the patients. Both sections could be successfully removed via a cervical incision, and no obvious complications were observed during the perioperative period. With careful planning and execution before surgery and meticulous operation during surgery, most retrosternal goiters can be safely treated by cervical approach.

Predictive role of intraoperative clinicopathological features of the central compartment in estimating lymph nodes metastasis status.

BACKGROUND: To explore the feasibility of immediate assessment, which focuses on clinicopathological characteristics of central lymph nodes (LNs) during operation. Moreover, to analyze the predictive effect of various evaluated indicators on the nature, quantities, and ratios of central lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC), to provide the basis for precise individualized central lymph node dissection (LND). METHODS: According to the inclusion and exclusion criteria, 1,271 PTC patients were selected in this cohort study. In the study, the clinical and pathological characteristics of the central LNs were evaluated by the treatment groups during the operation, which had a similar therapeutic experience. The parameters including the texture, volume, maximum/vertical meridian, extracapsular infiltration, adhesion or fusion, and nano-carbon staining status of the central LNs were collected. According to the pathological results after the operation, the nature, quantities, and rate of LNM in the central compartment were counted. The relationship between these parameters and metastatic nature, quantities, and ratios was analyzed and compared. RESULTS: Univariate analysis showed that when the larger size of LNs (especially the maximum meridian >0.9 cm), extracapsular infiltration, adhesion and fusion being found, A higher possibility of LNM in the central compartment (P<0.05), higher number and ratio of metastasis (P<0.05) might be existed. Moreover, more than two positive LNs were more likely to appear. Maximum/vertical meridian <2 and texture hardness could not indicate metastasis (P>0.05) and higher metastasis ratio (P>0.05), but could only be used as a reference for the existence of metastasis (P<0.05). The number of metastatic LNs dissected by carbon nanoparticles during operation could be increased (P<0.05). However, it has no predictive effect on the nature and rate of LNM (P>0.05). Multivariate analysis showed that larger central LNs, the maximum meridian >0.9 cm, extracapsular infiltration, adhesion, and fusion were independent prognostic factors for central LNM (P<0.05), which could be used as a predictor of the properties of central LNs during operation. At the same time, larger LNs, extracapsular infiltration, adhesion and fusion, and nano-carbon black staining were independent predictors of LNM in the central compartment, which are more than two (P<0.05). CONCLUSIONS: It is practical and feasible to evaluate the clinicopathological features of central LNs immediately during the operation. Intraoperative assessment of central LNs volume, capsular infiltration, maximum/vertical meridian, carbon nano tracking, and adhesion and fusion has predictive effects differently on the nature, quantities, and ratios of central LNM. In order to make an early prediction and advance judgment, surgeons should pay more attention to evaluate clinicopathological features of central LNs during operation, which is conducive to the proper implementation of LND in the central compartment.

Primary repair and reconstruction of tumor defects in parotid masseter region: a report of 58 cases.

BACKGROUND: The purpose of this study was to investigate the one-stage reconstruction of primary or secondary neoplastic defects in the parotid masseter area. METHODS: Fifty-eight cases of soft tissue defects reconstruction caused by tumors in the parotid masseter area from 2014 to 2018 were analyzed. The minimum area of defect was 4 cm × 5 cm, and the maximum area was 12 cm × 12 cm. According to the characteristics of the defect and the condition of the patient, the individualized repair method was adopted. Among them, 40 cases were repaired with adjacent flaps, 6 cases with pectoralis major myocutaneous flaps and 12 cases with free flaps. RESULTS: All of the 58 flaps survived, 2 of which were recurrent after radiotherapy. The skin flaps healed poorly with the surrounding skin and healed entirely after 2 weeks of dressing change. The patients were followed up for 6 months to 4 years. One patient with parotid carcinoma recurred locally, one with squamous cell carcinoma of parotid gland died of lung metastasis, and one with malignant melanoma died of brain metastasis. CONCLUSIONS: The soft tissue defect in the parotid masseter region caused by the tumor is common. It is necessary to combine the characteristics of the defect and the general situation of the patient clinically. The individualized method of repair and reconstruction can achieve the effect of a radical cure of the tumor and the consideration of local morphology and function.

Parthenolide Inhibits the Proliferation of MDA-T32 Papillary Thyroid Carcinoma Cells in Vitro and in Mouse Tumor Xenografts and Activates Autophagy and Apoptosis by Downregulation of the Mammalian Target of Rapamycin (mTOR)/PI3K/AKT Signaling Pathway.

BACKGROUND This study aimed to examine the effects of the sesquiterpene lactone, parthenolide, on migration, autophagy, and apoptosis of MDA-T32 human papillary thyroid carcinoma cells in vitro and in mouse tumor xenografts. MATERIAL AND METHODS Cell proliferation and viability of MDA-T32 human papillary thyroid carcinoma cells were determined by MTT assay, and cell migration was studied using a transwell assay. Fluorescence microscopy using acridine orange (AO) and ethidium bromide (EB) staining evaluated apoptosis. Transmission electron microscopy was used to study the effects of parthenolide on autophagy, and Western blot examined the levels of autophagy-associated proteins, including Bax, Bcl-2, and LC3-ll. Mice (n=10) were injected with 5×106 MDA-T32 cells subcutaneously into the left flank, and xenograft tumors were grown for six weeks. Control untreated mice (n=5) were compared with treated mice (n=5) given parthenolide three times per week. RESULTS Parthenolide resulted in a dose-dependent reduction in viability and cell migration of MDA-T32 cells, with a half-maximal inhibitory concentration (IC50) of 12 µM. AO and EB staining showed that parthenolide induced cell apoptosis and electron microscopy identified autophagosomes in MDA-T32 cells. Parthenolide induced increased expression of the autophagocytic proteins, LC3-II and beclin-1, had a dose-dependent inhibitory effect on the mTOR/PI3K/AKT cascade in MDA-T32 cells and inhibited the growth of the mouse xenograft tumors in vivo. CONCLUSIONS Parthenolide inhibited the growth and migration of MDA-T32 human papillary thyroid carcinoma cells in vitro and mouse tumor xenografts and activated autophagy and apoptosis by downregulation of the mTOR/PI3K/AKT signaling pathway.

[Missing Data Replacement Methods in Different Scenarios].

OBJECTIVE: To compare the effect of different approaches of missing data replacement on the regression coefficient estimates r of "length of stay" on "hospital expenditure". METHODS: Data were extracted from the medical records of patients with head and neck neoplasms who were admitted to Sichuan Cancer Hospital. R 3.4.1 was used for generating and processing simulated datasets. Various scenarios were established by setting up different proportions of missing data and missing mechanisms using Monte Carlo method. Three strategies were tested for replacing missing data: Complete Case method,Expectation Maximization (EM),and Markov Chain Monte Carlo method (MCMC). The regression coefficient estimates r of standardized "length of stay" on standardized logarithmic "hospital expenditure" were calculated using these strategies and compared with that of the original complete dataset,in terms of their accuracy (magnitude of differences in r) and precision (differences in the standard error of r). RESULTS: The three replacement methods were all acceptable (within the limit rc±0.5 sc) when missing data were generated using MAR (2∶1) mechanism,or less than 30% data were simulated as missing using the MCAR and MAR (1∶2) mechanism. The EM method had the best estimation precision. CONCLUSION: Missing data replacement should consider the proportion of missing data and potential mechanisms involved.