Reversible Transition of Semiconducting PtSe2 and Metallic PtTe2 for Scalable All-2D Edge-Contacted FETs.

Two-dimensional (2D) transition metal dichalcogenide (TMD) layers are highly promising as field-effect transistor (FET) channels in the atomic-scale limit. However, accomplishing this superiority in scaled-up FETs remains challenging due to their van der Waals (vdW) bonding nature with respect to conventional metal electrodes. Herein, we report a scalable approach to fabricate centimeter-scale all-2D FET arrays of platinum diselenide (PtSe2) with in-plane platinum ditelluride (PtTe2) edge contacts, mitigating the aforementioned challenges. We realized a reversible transition between semiconducting PtSe2 and metallic PtTe2 via a low-temperature anion exchange reaction compatible with the back-end-of-line (BEOL) processes. All-2D PtSe2 FETs seamlessly edge-contacted with transited metallic PtTe2 exhibited significant performance improvements compared to those with surface-contacted gold electrodes, e.g., an increase of carrier mobility and on/off ratio by over an order of magnitude, achieving a maximum hole mobility of ∼50.30 cm2 V-1 s-1 at room temperature. This study opens up new opportunities toward atomically thin 2D-TMD-based circuitries with extraordinary functionalities.

Tachol1 QTL on mouse chromosome 1 is responsible for hypercholesterolemia and diet-induced obesity.

Hypercholesterolemia raises the risk for cardiovascular complications and overall health. Hypercholesterolemia is common, affecting 10% of the general population of the US, and heritable. Most individuals with hypercholesterolemia have a polygenic predisposition to the condition. Previously we identified a quantitative trait locus, Tachol1, linked to hypercholesterolemia on mouse chromosome 1 (Chr1) in a cross between C57BL/6J (B6) and TALLYHO/JngJ (TH) mice, a polygenic model for human obesity, type 2 diabetes and hyperlipidemia. Subsequently, using congenic mice that carry a TH-derived genomic segment of Chr1 on a B6 background, we demonstrated that the distal segment of Chr1, where Tachol1 maps, is necessary to cause hypercholesterolemia, as well as diet-induced obesity. In this study, we generated overlapping subcongenic lines to the distal segment of congenic region and characterized subcongenic mice carrying the smallest TH region of Tachol1, ~ 16.2 Mb in size (B6.TH-Chr1-16.2 Mb). Both male and female B6.TH-Chr1-16.2 Mb mice showed a significantly increased plasma total cholesterol levels compared to B6 on both chow and high fat (HF) diet. B6.TH-Chr1-16.2 Mb mice also had greater fat mass than B6 on HF diet, without increasing food intake. The gene and protein expression levels of absent in melanoma 2 (Aim2) gene were significantly upregulated in B6.TH-Chr1-16.2 Mb mice compared to B6. In summary, we confirmed the effect of Tachol1 on hypercholesterolemia and diet-induced obesity using subcongenic analysis.

Longer peripheral-track lesions are associated with instability after arthroscopic Bankart repair.

BACKGROUND: The glenoid track concept has enabled the categorization of Hill-Sachs lesions (HSLs) into on-track lesions and off-track lesions. Furthermore, among the on-track lesions, further categorization has been established based on the distance from the medial edge of the Hill-Sachs lesion to the medial edge of the glenoid track, into peripheral-track lesions and central-track lesions. Recent studies on peripheral-track lesions and central-track lesions within the glenoid track have shown inconsistencies in failure rates, which deserves further investigation. METHODS: A retrospective cohort comparison of patients who underwent arthroscopic Bankart repair between 2015 and 2020 was performed. 102 patients with peripheral-track HSLs were included. The patients were divided into 2 groups based on the results of the postoperative apprehension test: the apprehension positive group (n = 30), and the apprehension negative group (n = 72). Using preoperative computed tomography (CT) and an image reconstruction program, 3-dimensional (3D) images were segmented to calculate the length, width, depth, and distance of the HSLs. A multivariate logistic regression was used to determine the risk factors of recurrence, for which odds ratio (OR) and 95% confidence interval (CI) were provided. RESULTS: A multivariate logistic regression analysis revealed that the length of the peripheral-track HSLs was a significant independent predictor of failure in this study. (OR 1.380; 95% CI 1.170-1.627; P < .001). The receiver operating characteristics curve (ROC) demonstrated a predictive power (area under the curve = 0.841) and a threshold value of 14.2 mm. CONCLUSION: Length was the only risk factor for the recurrent instability of peripheral-track HSLs after ABR. In the context of surgical decision-making, utilizing the glenoid track concept, medical practitioners may need to evaluate instability by considering the length as a continuous factor, while differentiating between peripheral-track and central-track classifications.

Patterns of Anterior Inferior Tibiofibular Ligament Avulsion Fracture Accompanied by Ankle Fracture.

The anterior inferior tibiofibular ligament (AITFL) avulsion fracture accompanying an ankle fracture can compromise ankle stability, necessitating accurate evaluation and a clear understanding of its pathophysiology.. The aim of this study was to investigate the association between AITFL avulsion fracture and Lauge-Hansen, Wagstaffe classification. A retro-prospective study was conducted at a university-affiliated tertiary care medical center. We selected 128 patients who underwent surgery at our institution between January 2013 and July 2017 and analyzed the association between AITFL avulsion fracture and the foot position. According to the modified Wagstaffe classification system, there were 39 cases of type II, followed by 9 cases of type III and 8 cases of type IV. Of the7 pronation-abduction fractures, 3 were AITFL avulsion fracture (43%), while of the 21 pronation-external rotation fractures, 9 were AITFL avulsion fracture (43%). Of the 95 supination-external rotation fractures, there were 56 cases (59%) of AITFL avulsion fractures. Of the pronation fractures, 0% were fibular avulsion fractures and 43% were tibial avulsion fractures. Of the supination fractures, 44% were fibular avulsion fractures and 16% were tibial avulsion fracture. The difference in the ratio of fibular to tibial avulsion fractures between pronation and supination fractures was significant (p < .001). These results suggest that tibial avulsion fractures of type IV in the modified Wagstaffe classification and pronation fractures occur due to collision with the anterolateral corners of the distal bone when the talus externally rotates. Moreover, in cases of pronation fractures, a new type of AITFL avulsion fracture has been observed.

Selection Criteria for Completion Thyroidectomy in Follicular Thyroid Carcinoma Using Primary Tumor Size and TERT Promoter Mutational Status.

BACKGROUND: A stepwise surgical approach with hemithyroidectomy and completion thyroidectomy was used to achieve definite characterization of follicular thyroid carcinoma (FTC). Choosing appropriate candidates for completion thyroidectomy has been controversial. OBJECTIVE: The aim of this study was to clarify the selection criteria for completion thyroidectomy using telomerase reverse transcriptase (TERT) promoter mutation. METHODS: A total of 87 FTC patients who had information about TERT promoter mutation from August 1995 to November 2020 were investigated. The cumulative risk of initial distant metastasis, disease recurrence, and cancer-specific death according to primary tumor size in each of the World Health Organization (WHO) 2017 classifications were calculated. RESULTS: Of the 87 patients, 8 (9.2%) had initial distant metastasis and 15 (17.2%) had persistent disease or developed structural recurrence. The threshold diameter for initial distant metastasis, disease recurrence, and cancer-specific death was 2 cm in minimally invasive FTC (MI-FTC) with mutant TERT (M-TERT) and in encapsulated angioinvasive FTC (EA-FTC) with M-TERT, while that in MI-FTC with wild-type TERT (WT-TERT) and EA-FTC with WT-TERT was 4 cm. The cumulative risk of initial distant metastasis, disease recurrence, and cancer-specific death according to primary tumor size in each WHO 2017 classification was significantly different only in patients with WT-TERT (p = 0.001, p = 0.019, and p = 0.005, respectively). CONCLUSIONS: The data suggest 2 cm as a critical threshold diameter for performance of completion thyroidectomy in MI-FTC with M-TERT and EA-FTC with M-TERT. TERT promoter mutational status can help select candidates for completion thyroidectomy.

Association of clinical manifestations of secondary lymphedema and lymph node dissection sites in the lower extremities of patients with melanoma.

BACKGROUND: Lymphedema is a chronic, debilitating disease that often requires life-long management. Predicting clinical manifestations and prognosis is crucial in clinical practice because the treatment of lymphedema should be individualized for best clinical outcome. The aim of this study is to explore the location and severity of lymphedema secondary to inguinal and/or iliac lymph node dissection (LND) in patients with melanoma. METHODS: Patients with melanoma who received LND at a single tertiary medical center between 1 January 2010 and 31 September 2022 were retrospectively reviewed. Patient who received inguinal LND only were designate as the inguinal group while those who received both ilioinguinal LND were included in the ilioinguinal group. Volumetric measurement was used to objectify the severity and location of lymphedema. Clinical data was acquired for 12-15 months of follow-up. RESULTS: Among 81 patients, 43 (53%) had developed lymphedema in the lower extremities at an average of 33 days after the surgery. Initially, patients manifested with medial thigh lymphedema in the inguinal group while patients were presented with whole leg lymphedema in the ilioinguinal group. Lower leg volume of the ilioinguinal group was significantly higher than the inguinal group. After more than 12 months of lymphedema treatment, upper leg volume was higher in the ilioinguinal group than the inguinal group (12.7% vs 5.4%, p < 0.05). CONCLUSION: Lymphedema developed in early post-op period. The ilioinguinal group presented with a larger volume of lymphedema in the distal area of the legs. Even after sufficient treatment, predominant lymphedema remained in the proximal leg for the ilioinguinal group. Patients with both inguinal and iliac LND were associated with more severe lymphedema. Based on the dissection sites, the clinical manifestations and prognosis of leg lymphedema can vary widely. Thus, clinicians should consider the dissection site when approaching melanoma patients with lymphedema.

Influence of joint volume on range of motion after arthroscopic rotator cuff repair.

BACKGROUND: Capsular contracture is a well-known etiology in the primary stiff shoulder; thus capsular contracture and resultant decreased joint volume could lead to postoperative stiffness, which is a commonly reported morbidity after arthroscopic rotator cuff repair (ARCR). The purpose of this study was (1) to quantify the joint volume (total joint volume and each quadrant compartmental volume) using computed tomography arthrography (CTA) and (2) to demonstrate the relationship between joint volume and postoperative range of motion (ROM) after ARCR. MATERIALS AND METHODS: Eighty-three patients (60 ± 5.11 years, men = 26, women = 57) who had undergone ARCR between January 2015 to December 2020 due to small to medium full-thickness tear and followed by CTA 6 months postoperatively were retrospectively reviewed. An image reconstruction program (3D Slicer, version 4.11.2 software) was used to calculate the joint volume (total joint volume and quadrant compartment joint volumes; anteroinferior, anterosuperior, posterosuperior and posteroinferior). For shoulder ROM, data including scaption (Sc), external rotation on side (ERs), external rotation at 90° (ER90), and internal rotation on back (IRb) were collected 6 months postoperatively. An evaluation of the correlation between joint volume and each shoulder motion was performed. RESULTS: There were moderate correlations between the total joint volume and each motion (Sc: Pearson coefficient, 0.32, p = 0.0047; ERs: Pearson coefficient, 0.24, p = 0.0296; ER90: Pearson coefficient, 0.33, p = 0.0023; IRb: Pearson coefficient, 0.23, p = 0.0336). Among the quadrant compartments, the anteroinferior (Sc: Pearson coefficient, 0.26, p = 0.0199; ERs: Pearson coefficient, 0.23, p = 0.0336; ER90: Pearson coefficient, 0.25, p = 0.0246; IRb: Pearson coefficient, 0.26, p = 0.0168) and posterosuperior (Sc: Pearson coefficient, 0.24, p = 0.029; ER90: Pearson coefficient, 0.29, p = 0.008; IRb: Pearson coefficient, 0.22, p = 0.0491) and posteroinferior (Sc: Pearson coefficient, 0.30, p = 0.0064; ER90: Pearson coefficient, 0.29, p = 0.0072) showed moderate correlations with each shoulder motion. CONCLUSION: Total joint volume, anteroinferior compartment joint volume, posterosuperior compartment joint volume and posteroinferior compartment joint volume were related to postoperative ROM after ARCR. Perioperative methods to increase the joint volume, especially the anteroinferior, posterosuperior and posteroinferior parts of the capsule may prevent postoperative stiffness after ARCR. LEVEL OF EVIDENCE: Level III; Retrospective Case-Control Study.

Parameters affecting improvement of excessive daytime sleepiness in obstructive sleep apnea patients.

OBJECTIVES: Obstructive sleep apnea (OSA) is a sleep-related breathing disorder caused by repetitive obstruction of the upper airway; this impairs gaseous exchange, resulting in hypoxia, hypercapnia, and frequent arousals. Excessive daytime sleepiness (EDS) is a common daytime symptom of OSA. EDS manifests as fatigue and impaired attention, leading to poor performance at work and falling asleep while driving, which is a major socioeconomic problem. Therefore, it is important to properly treat EDS and accurately predict the response to treatment. However, few studies have compared OSA patients showing and not showing improvement in EDS. Therefore, this study aimed to objectively analyze and compare EDS improvement and non-improvement groups. SUBJECTS AND METHODS: We retrospectively reviewed the medical records of 57 OSA patients with EDS. Patients were divided into two groups according to the improvement in EDS after positive airway pressure (PAP) device treatment. We analyzed differences in clinical records including patients' age, sex, history of smoking, hypertension, diabetes, myocardial infarction, and cerebrovascular disease between the two groups. Systolic, diastolic blood pressure, blood test including blood glucose, total cholesterol, high- and low-density lipoprotein cholesterol, and triglyceride levels were also analyzed. Polysomnography (PSG) data, PAP device treatment compliance and scores of questionnaires related to various psychiatric symptoms, subjective sleep quality between the two groups were also analyzed. RESULTS: There was no statistically significant difference in age, gender, or past medical history between the two groups. Systolic and diastolic blood pressure, and blood test results, were also not significantly different. Among the questionnaires related to various psychiatric symptoms, the groups showed statistically significant differences in Social Avoidance and Distress Scale (SADS) and Fear of Negative Evaluation (FNE) scores (P = 0.001 and 0.020, respectively). The group differences in the scores on the other questionnaires were not significantly different. Among the PSG items, significant group differences were observed in the percentage of stage 2 non-REM sleep (N2%, P = 0.023), apnea index (AI, P = 0.005), apnea-hypopnea index (AHI, P = 0.023), and frequency of 3 % oxygen desaturation (ODI3, P = 0.001). No obesity-related parameters showed significant group differences. The percentage of days on which a PAP device was used (out of 90 days; PAP%) and percentage of days on which a PAP device was used for >4 h (Time4%) did not differ significantly. CONCLUSIONS: The SADS, FNE, AI, AHI, N2%, and ODI3 parameters differed significantly between the EDS improvement and non-improvement groups. These parameters may help clinicians treat and predict the prognosis of patients suffering with EDS.

The Role of ROR1 in Chemoresistance and EMT in Endometrial Cancer Cells.

Background and Objectives: Receptor tyrosine kinase-like orphan receptor type 1 (ROR1) plays a critical role in embryogenesis and is overexpressed in many malignant cells. These characteristics allow ROR1 to be a potential new target for cancer treatment. The aim of this study was to investigate the role of ROR1 through in vitro experiments in endometrial cancer cell lines. Materials and Methods: ROR1 expression was identified in endometrial cancer cell lines using Western blot and RT-qPCR. The effects of ROR1 on cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) markers were analyzed in two endometrial cancer cell lines (HEC-1 and SNU-539) using either ROR1 silencing or overexpression. Additionally, chemoresistance was examined by identifying MDR1 expression and IC50 level of paclitaxel. Results: The ROR1 protein and mRNA were highly expressed in SNU-539 and HEC-1 cells. High ROR1 expression resulted in a significant increase in cell proliferation, migration, and invasion. It also resulted in a change of EMT markers expression, a decrease in E-cadherin expression, and an increase in Snail expression. Moreover, cells with ROR1 overexpression had a higher IC50 of paclitaxel and significantly increased MDR1 expression. Conclusions: These in vitro experiments showed that ROR1 is responsible for EMT and chemoresistance in endometrial cancer cell lines. Targeting ROR1 can inhibit cancer metastasis and may be a potential treatment method for patients with endometrial cancer who exhibit chemoresistance.

Molecular classification of follicular thyroid carcinoma based on TERT promoter mutations.

Follicular thyroid carcinoma (FTC) has different clinicopathological characteristics than papillary thyroid carcinoma. However, there are no independent systems to predict cancer-specific survival (CSS) in FTC. Telomerase reverse transcriptase (TERT) promoter mutations are associated with tumor aggressiveness. Thus, it could be a potential prognostic marker. The aim of this study was to refine the CSS risk prediction using TERT promoter mutations in combination with the fourth edition of World Health Organization (WHO 2017) morphological classification. We investigated 77 FTC patients between August 1995 and November 2020. Cox regression was used to calculate hazard ratios to derive alternative groups. Disease-free survival (DFS) and CSS predictability were compared using Proportion of variation explained (PVE) and C-index. CSS was significantly different in encapsulated angioinvasive (EA)-FTC patients stratified by TERT promoter mutations [wild-type (WT-TERT) vs. mutant (M-TERT); P < 0.001] but not in minimally invasive (MI)-FTC and widely invasive (WI)-FTC patients (P = 0.691 and 0.176, respectively). We defined alternative groups as follows: Group 1 (MI-FTC with WT-TERT and M-TERT; EA-FTC with WT-TERT), Group 2 (WI-FTC with WT-TERT), and Group 3 (EA-FTC with M-TERT; WI-FTC with M-TERT). Both PVE (22.44 vs. 9.63, respectively) and C-index (0.831 vs. 0.731, respectively) for CSS were higher in the alternative groups than in the WHO 2017 groups. Likewise, both PVE (27.1 vs. 14.9, respectively) and C-index (0.846 vs. 0.794, respectively) for DFS were also higher in the alternative groups than in the WHO 2017 groups. Alternative group harmonizing of the WHO 2017 classification and TERT promoter mutations is effective in predicting CSS in FTC patients, thereby improving DFS predictability.

Large-area vertically aligned 2D MoS2layers on TEMPO-cellulose nanofibers for biodegradable transient gas sensors.

Crystallographically anisotropic two-dimensional (2D) molybdenum disulfide (MoS2) with vertically aligned (VA) layers is attractive for electrochemical sensing owing to its surface-enriched dangling bonds coupled with extremely large mechanical deformability. In this study, we explored VA-2D MoS2layers integrated on cellulose nanofibers (CNFs) for detecting various volatile organic compound gases. Sensor devices employing VA-2D MoS2/CNFs exhibited excellent sensitivities for the tested gases of ethanol, methanol, ammonia, and acetone; e.g. a high response rate up to 83.39% for 100 ppm ethanol, significantly outperforming previously reported sensors employing horizontally aligned 2D MoS2layers. Furthermore, VA-2D MoS2/CNFs were identified to be completely dissolvable in buffer solutions such as phosphate-buffered saline solution and baking soda buffer solution without releasing toxic chemicals. This unusual combination of high sensitivity and excellent biodegradability inherent to VA-2D MoS2/CNFs offers unprecedented opportunities for exploring mechanically reconfigurable sensor technologies with bio-compatible transient characteristics.

Is total thyroidectomy with bilateral central neck dissection the only surgery for papillary thyroid carcinoma patients with clinically involved central nodes?

BACKGROUND: In clinical practice, we often observed that patients who underwent total thyroidectomy due to clinically involved nodal disease (cN1a) actually had less extensive CLNM on final pathology. This study investigates whether total thyroidectomy and therapeutic bilateral CND are necessary for all PTC patients with cN1a. METHODS: This study retrospectively reviewed 899 PTC patients who underwent total thyroidectomy with bilateral CND from January 2012 to June 2017. The patients were divided into two groups according to pre-operative central lymph node (CLN) status: cN0, no suspicious CLNM; cN1a, suspicious CLNM. We compared the clinicopathological features of these two groups. RESULTS: There was no significant difference in recurrence between cN0 and cN1a groups after a mean follow-up time of 59.1 months. Unilateral cN1a was related to the largest central LN size ≥ 2 mm (OR = 3.67, p < 0.001) and number of CLNM > 5(OR = 2.24, p = 0.006). On the other hand, unilateral cN1a was not associated with an increased risk of contralateral lobe involvement (OR = 1.35, p = 0.364) and contralateral CLNM (OR = 1.31, p = 0.359). Among 106 unilateral cN1a patients, 33 (31.1%) were found to be pN0 or had ≤ 5 metastatic CLNs with the largest node smaller than 2 mm. CONCLUSIONS: Most cN1a patients were in an intermediate risk group for recurrence and required total thyroidectomy. However, lobectomy with CND should have performed in approximately 30% of the cN1a patients. Pre-operative clinical examination, meticulous radiologic evaluation, and intra-operative frozen sections to check the nodal status are prerequisites for this approach.

Chrysophanol-Induced Autophagy Disrupts Apoptosis via the PI3K/Akt/mTOR Pathway in Oral Squamous Cell Carcinoma Cells.

Background and Objectives: Natural products are necessary sources for drug discovery and have contributed to cancer chemotherapy over the past few decades. Furthermore, substances derived from plants have fewer side effects. Chrysophanol is an anthraquinone derivative that is isolated from rhubarb. Although the anticancer effect of chrysophanol on several cancer cells has been reported, studies on the antitumor effect of chrysophanol on oral squamous-cell carcinoma (OSCC) cells have yet to be elucidated. Therefore, in this study, we investigated the anticancer effect of chrysophanol on OSCC cells (CAL-27 and Ca9-22) via apoptosis and autophagy, among the cell death pathways. Results: It was found that chrysophanol inhibited the growth and viability of CAL-27 and Ca9-22 and induced apoptosis through the intrinsic pathway. It was also found that chrysophanol activates autophagy-related factors (ATG5, beclin-1, and P62/SQSTM1) and LC3B conversion. That is, chrysophanol activated both apoptosis and autophagy. Here, we focused on the roles of chrysophanol-induced apoptosis and the autophagy pathway. When the autophagy inhibitor 3-MA and PI3K/Akt inhibitor were used to inhibit the autophagy induced by chrysophanol, it was confirmed that the rate of apoptosis significantly increased. Therefore, we confirmed that chrysophanol induces apoptosis and autophagy at the same time, and the induced autophagy plays a role in interfering with apoptosis processes. Conclusions: Therefore, the potential of chrysophanol as an excellent anticancer agent in OSCC was confirmed via this study. Furthermore, the combined treatment of drugs that can inhibit chrysophanol-induced autophagy is expected to have a tremendous synergistic effect in overcoming oral cancer.

Meta-Analysis of Survival Effects of Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1).

Background and Objectives: Identification and targeting of membrane proteins in tumor cells is one of the key steps in the development of cancer drugs. The receptor tyrosine kinase-like orphan receptor (ROR) type 1 is a type-I transmembrane protein expressed in various cancer tissues, which is in contrast to its limited expression in normal tissues. These characteristics make ROR1 a candidate target for cancer treatment. This study aimed to identify the prognostic value of ROR1 expression in cancers. Materials and Methods: We conducted a comprehensive systematic search of electronic databases (PubMed) from their inception to September 2021. The included studies assessed the effect of ROR1 on overall survival (OS) and progression-free survival (PFS). Hazard ratios (HR) from collected data were pooled in a meta-analysis using Revman version 5.4 with generic inverse-variance and random effects modeling. Results: A total of fourteen studies were included in the final analysis. ROR1 was associated with worse OS (HR 1.95, 95% confidence interval (CI) 1.50−2.54; p < 0.001) with heterogeneity. The association between poor OS and ROR1 expression was high in endometrial cancer, followed by ovarian cancer, and diffuse large B cell lymphoma. In addition, ROR1 was associated with poor PFS (HR 1.84, 95% CI 1.60−2.10; p < 0.001), but heterogeneity was not statistically significant. In subgroup analysis, high ROR1 expression showed a significantly higher rate of advanced stage or lymph node metastasis. Conclusions: This meta-analysis provides evidence that ROR1 expression is associated with adverse outcome in cancer survival. This result highlights ROR1 as a target for developmental therapeutics in cancers.

Ursodeoxycholic acid shows antineoplastic effects in bile duct cancer cells via apoptosis induction; p53 activation; and EGFR-ERK, COX-2, and PI3K-AKT pathway inhibition.

Unlike in normal cells, ursodeoxycholic acid (UDCA) causes apoptosis rather than protection in cancer cells. Aim of this study was to demonstrate whether UDCA actually inhibits proliferation and induces apoptosis in bile duct cancer cells; the effect of UDCA on the expression of COX-2, PI3K/AKT, ERK, and EGFR; how UDCA affects cancer cell invasiveness and metastasis, since these effects are not established in bile duct cancer cells. SNU-245 cells (human extrahepatic bile duct cancer cells) were cultured. MTT assays were performed to evaluate the effect of UDCA on the cell proliferation. A cell death detection enzyme-linked immunosorbent assay and a caspase-3 activity assay were used to determine apoptosis. Western blot analysis measured expression levels of various proteins. The invasiveness of the cancer cells was evaluated by invasion assay. In cultured bile duct cancer cells, UDCA suppressed cell proliferation in bile duct cancer cells by inducing apoptosis and p53 activation, blocking deoxycholic acid (DCA)-induced activated EGFR-ERK signaling and COX-2, inhibiting DCA-induced activated PI3K-AKT signaling, and suppressing the invasiveness of bile duct cancer cells. In addition, a MEK inhibitor impaired UDCA-induced apoptosis in bile duct cancer cells. UDCA has antineoplastic and apoptotic effects in bile duct cancer cells. Thus, UDCA could be a chemopreventive agent in patients with a high risk of cancer, and/or a therapeutic option that enhances other chemotherapeutics.

Pegteograstim prophylaxis for chemotherapy-induced neutropenia and febrile neutropenia: a prospective, observational, postmarketing surveillance study in Korea.

PURPOSE: This observational study aimed to evaluate the safety and efficacy of pegteograstim prophylaxis in patients with lymphoma and solid malignancies. METHODS: This study was conducted at 18 sites in Korea between November 2015 and August 2018. RESULTS: In total, 611 patients (female, 61.2%) with a median age of 58 (range, 18-88) years were included. Most patients had lymphomas (n = 371, 60.7%) and breast cancer (n = 230, 37.6%) and were administered R-CHOP21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone per 21 days) (n = 284, 46.5%) and AC (doxorubicin and cyclophosphamide) (n = 177, 29.0%). The total pegteograstim dose in the 611 patients was 14,970 mg (2495 doses), with each patient receiving an average daily dose of 6.0 mg. Neutropenia grade 4 occurred in 97 patients (15.9%), and febrile neutropenia (FN) occurred in 31 patients (5.1%). Among the 611 patients, 267 patients (43.7%) developed 882 adverse events (AEs), and 11 patients (1.8%) experienced 18 adverse drug reactions (ADRs). There were 62 patients (10.2%) who experienced 81 cases of serious adverse events (SAEs), with FN and pneumonia being the most frequent at 14 and 13 episodes, respectively, in 13 patients (2.1%). Meanwhile, 1 patient (0.2%) developed 2 episodes of serious ADRs (grade 1 and grade 2 hypotension). No safety concerns in the elderly and patients with liver and/or renal disease were identified. CONCLUSION: The prophylactic use of pegteograstim might have good overall safety and efficacy in patients with lymphomas and solid malignancies in routine clinical practice, even in those who are elderly and have liver and renal diseases.

Peroneal Tendon Subluxation and Dislocation in Calcaneus Fractures.

The present study investigated the relationship between type of calcaneal fractures and subluxation or dislocation of peroneal tendon. Also, we investigated clinical outcomes of patients with both calcaneal fractures and dislocations or subluxations of peroneal tendons in early surgical treatments (at the time of surgery for calcaneal fractures) and delayed surgical treatment (at the time of surgery for calcaneal plate removal) for dislocations or subluxations of peroneal tendons. We included 151 patients with calcaneal fractures who were followed for ≥2 years after surgery. Among them, 21 cases (13.9%) required reduction for peroneal tendon subluxation or dislocation. Reductions of peroneal tendons were performed at the time of surgery for calcaneal fractures in 11 cases, whereas the other 10 cases were performed during surgery for calcaneal implant removal. As classified by Essex-Lopresti, 94 cases (62.3%) were joint depression type and 17 (18.1%) were accompanied by dislocations or subluxations of peroneal tendons, whereas 57 (37.7%) were tongue type and 4 (7.0%) were accompanied by dislocations or subluxations of peroneal tendons. As classified by the Sanders system, 96 cases (63.6%) were Sanders A fracture lines, and 18 (18.8%) were accompanied by dislocations or subluxations of peroneal tendons. In 55 cases (36.4%) without Sanders A fracture lines, 3 (5.5%) were accompanied by dislocations or subluxations of peroneal tendons. In conclusion, calcaneal fractures with peroneal tendon dislocations are more common in joint depression type and Sander A type. Also, after a ≥2-year follow-up period, there were no significant differences in visual analog scale or foot and ankle outcome score whether reduction of peroneal tendons was done with reduction of fracture or removal of implant of calcaneus.

Role of Luteolin-Induced Apoptosis and Autophagy in Human Glioblastoma Cell Lines.

Background and Objectives: Malignant glioblastoma (GBM) is caused by abnormal proliferation of glial cells, which are found in the brain. The therapeutic effects of surgical treatment, radiation therapy, and chemo-therapy against GBM are relatively poor compared with their effects against other tumors. Luteolin is abundant in peanut shells and is also found in herbs and other plants, such as thyme, green pepper, and celery. Luteolin is known to be effective against obesity and metabolic syndrome. The anti-inflammatory, and anti-cancer activities of luteolin have been investigated. Most studies have focused on the antioxidant and anti-inflammatory effects of luteolin, which is a natural flavonoid. However, the association between the induction of apoptosis by luteolin in GBM and autophagy has not yet been investigated. This study thus aimed to confirm the occurrence of luteolin-induced apoptosis and autophagy in GBM cells and to assess their relationship. Materials and Methods: A172 and U-373MG glioblastoma cell lines were used for this experiment. We confirmed the apoptosis effect of Luteolin on GBM cells using methods such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, immunofluorescence, Flow cytometry (FACS) western blot, and real-time quantitative PCR (qPCR). Results: In the luteolin-treated A172 and U-373MG cells, cell viability decreased in a concentration- and time-dependent manner. In addition, in A172 and U-373MG cells treated with luteolin at concentrations greater than 100 µM, nuclear fragmentation, which is a typical morphological change characterizing apoptosis, as well as fragmentation of caspase-3 and Poly (ADP-ribose) polymerase (PARP), which are apoptosis-related factors, were observed. Autophagy was induced after treatment with at least 50 µM luteolin. Inhibition of autophagy using 3MA allowed for a low concentration of luteolin to more effectively induce apoptosis in A172 and U-373MG cells. Conclusions: Results showed that luteolin induces apoptosis and autophagy and that the luteolin-induced autophagy promotes cell survival. Therefore, an appropriate combination therapy involving luteolin and an autophagy inhibitor is expected to improve the prognosis of GBM treatment.

Second-look arthroscopic findings and clinical outcomes after management of intra-articular lesions in acute ankle fractures with arthroscopy.

BACKGROUND: Anatomically surgical reduction of ankle fractures does not always result in a clinically favorable outcome. Arthroscopic examination combined with treatment of intra-articular lesion may related to clinical outcomes OBJECTIVES: The purpose of the present study was to review initial and second look arthroscopic finding of acute ankle fracture and to evaluate clinical outcomes. RESULTS: Lauge-Hansen classification system of ankle fractures included supination-external rotation type (n = 24), supination-adduction type (n = 3), pronation-external rotation type (n = 7), and pronation-abduction type (n = 6), total 40 ankles. Osteochondral lesions were found in 25 ankles (62%) with an initial arthroscopic finding of acute ankle fracture. Newly discovered chondral lesions in secondary arthroscopy were found in 17 cases. According to the Ferkel and Cheng staging at secondary arthroscopy, 4 of 25 ankles with osteochondral lesions of the talus were deteriorating (more than stage D). In terms of ICRS overall repair grades, 5 ankles (20%) were abnormal (grade III). Diffuse synovitis and arthrofibrosis were found in 12 and 7 ankles, respectively, in secondary arthroscopy, and correlations were found between AOFAS scores, VAS and intra-articular lesions. CONCLUSION: Second-look arthroscopic examination combined with treatment of intra-articular lesion such as arthrofibrosis and osteochondral lesion arising from ankle fracture surgery may consider to improve clinical outcomes.

The addition of metformin to systemic anticancer therapy in advanced or metastatic cancers: a meta-analysis of randomized controlled trials.

Preclinical studies have demonstrated that metformin has anticancer properties and act in additive or synergistic way when combined with anticancer agents. We conducted this meta-analysis of randomized clinical trials to evaluate the effect of metformin added to systemic anticancer therapy in patients with advanced or metastatic cancer. A computerized systematic electronic search was performed using PubMed, PMC, EMBASE, Cochrane Library, and Web of Science databases (up to June 2020). From nine randomized clinical trials, 821 patients were included in the pooled analyses of odds ratios (ORs) with 95% confidence intervals (CIs) for overall response rate (ORR) and hazard ratios (HRs) with 95% CIs for progression-free survival (PFS) and overall survival (OS). The concomitant use of metformin with systemic anticancer therapy did not increase tumor response (the pooled OR of ORR = 1.23, 95% CI: 0.89-1.71, p = 0.21), compared with anticancer therapy alone. In terms of survival, metformin added to anticancer agents failed to prolong PFS (HR = 0.95, 95% CI: 0.75-1.21, p = 0.68) and OS (HR = 0.97, 95% CI: 0.80-1.16, p = 0.71). In conclusion, this meta-analysis of randomized clinical trials indicates that the addition of metformin to systemic anticancer therapy has no clinical benefits in patients with advanced or metastatic cancer.