Epidemiology and Characteristics of Ankle and Foot Injuries in Electric Scooter-Related Accidents.

Background: The use of electric scooters (e-scooters) continues to increase as a simple, inexpensive means of transport, resulting in a sharp increase in the incidence of scooter-related accidents. No study to date has closely examined the injury extent to the lower leg, joints, and extremities from e-scooter-related accidents. Here, we investigated the epidemiology and injury patterns of such accidents, focusing on injuries to the ankle and foot. Methods: Based on data from a single tertiary hospital's database, the demographics of 563 patients with scooter-associated injuries were analyzed retrospectively. Among the patients, 229 patients who were injured by e-scooter riding were further investigated. Based on the data, the general demographics of whole scooter-associated injuries and the injury characteristics and fracture cases of the lower leg, ankle, and foot were analyzed. Results: During the 4-year study period, the number of patients injured by e-scooters increased every year. Lower extremities were the most common injury site (67.2%) among riders, whereas injuries to the head and neck (64.3%) were more common in riders of non-electric scooters. Among the lower leg, ankle, and foot injuries of riders (52 cases), the ankle joint (53.8%) was the most commonly injured site, followed by the foot (40.4%) and lower leg (21.2%). The fracture group scored significantly higher on the Abbreviated Injury Scale than the non-fracture group (p < 0.001). Among the fracture group (20 cases), ankle fractures (9 cases) were most common, including pronation external rotation type 4 injuries (4 cases) and pilon fractures (2 cases). Five patients (25%) had open fractures, and 12 patients (60%) underwent surgical treatment. Conclusions: The ankle and foot are the most common injury sites in e-scooter-related accidents. Given the high frequency and severity of e-scooter-related ankle and foot injuries, we suggest that more attention be paid to preventing these types of injuries with greater public awareness of the dangers of using e-scooters.

Maternal human papillomavirus infection and the risk of congenital malformations: A nationwide population-based cohort study.

Previous research has explored theories regarding the vertical transmission of human papillomavirus (HPV) infection and its association with adverse pregnancy and perinatal outcomes. However, the impact of maternal HPV infection on congenital anomalies (CAs) in offspring remains relatively understudied. We conducted a population-based cohort study linking the Taiwan Birth Registry, Taiwan Death Registry, and National Health Insurance Research Database, in which newborns born in Taiwan between 2009 and 2015 were included. We established a maternal HPV infection cohort comprising 37 807 newborns and matched them with a comparison group of 151 228 newborns at a 1:4 ratio based on index year, age, and sex. The study examined a composite outcome and subgroups of different types of congenital malformations. Differences in cumulative incidence of CAs were assessed using Kaplan-Meier curves and log-rank tests. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazard regressions. No significant association was found between HPV infection and the broad spectrum of CAs (aHR: 1.04, 95% confidence interval [CI]: 0.98-1.10; log-rank test p = 0.14). However, we observed a 19% increased risk of musculoskeletal CAs in the maternal HPV infection group (aHR: 1.19; 95% CI: 1.05-1.34) compared to those without maternal HPV exposure. Other factors, including the type of HPV (aHR: 0.65; 95% CI: 0.16-2.63), the timing of exposure (during or before pregnancy), and maternal age (aHR for <30 years: 1.02, 95% CI: 0.94-1.1; aHR for 30-39 years: 1.05, 95% CI: 0.99-1.11; aHR for ≥40 years: 0.88, 95% CI: 0.67-1.17), did not significantly affect the risk for any CA. In conclusion, gestation detection of HPV infection was associated with musculoskeletal CAs but not other major CAs. Prospective studies are warranted to elucidate the necessity of prenatal screening in populations at risk.

[Analysis of 41 cases of non-metastatic Ewing's sarcoma in children]. / 儿童非转移性尤文肉瘤41例分析.

OBJECTIVES: To summarize the clinical characteristics, treatment outcomes, and prognostic factors of children with non-metastatic Ewing's sarcoma (ES). METHODS: A retrospective analysis was conducted on the clinical data of 41 children with non-metastatic ES diagnosed and treated at the Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2018. All patients underwent chemotherapy based on the RMS-2009 protocol of the center, and local treatment such as surgery and/or radiotherapy was performed according to risk grouping. The Kaplan-Meier method was used to calculate the overall survival (OS) and event-free survival (EFS) rates. Univariate prognostic analysis was performed using the log-rank test, and multivariate analysis was conducted with Cox regression. RESULTS: Of the 41 children, 21 were male and 20 were female. The median age at diagnosis was 7.7 years (range: 1.2-14.6 years). The median follow-up time for patients with event-free survival was 68.1 months (range: 8.1-151.7 months). As of the last follow-up, 33 patients were in complete remission, and the overall 5-year EFS and OS rates were (78±6)% and (82±6)%, respectively. Univariate analysis by the log-rank test showed that a tumor diameter ≥8 cm, time from diagnosis to start of local treatment ≥16 weeks, and incomplete surgical resection were associated with poor prognosis (P<0.05). Multivariate Cox regression analysis indicated that incomplete surgical resection (HR=8.381, 95%CI: 1.681-41.801, P=0.010) was an independent risk factor for poor prognosis in children with ES. Secondary tumors occurred in 2 cases. CONCLUSIONS: A comprehensive treatment strategy incorporating chemotherapy, surgery, and radiotherapy can improve the prognosis of children with ES. Poor prognosis is associated with an initial tumor diameter ≥8 cm, while complete surgical resection and early initiation of local treatment can improve outcomes.

A novel phthalein component ameliorates neuroinflammation and cognitive dysfunction by suppressing the CXCL12/CXCR4 axis in rats with vascular dementia.

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanxiong, a plant of the Umbelliferae family, is a genuine medicinal herb from Sichuan Province. Phthalides are one of its main active components and exhibit good protective effect against cerebrovascular diseases. However, the mechanism by which phthalides exert neuroprotective effects is still largely unclear. AIM OF THE STUDY: In this study, we extracted a phthalein component (named as QBT) from Ligusticum Chuanxiong, and investigated its neuroprotective effects against vascular dementia (VaD) rats and the underlying mechanism, focusing on the chemokine 12 (CXCL12)/chemokine (C-X-C motif) receptor 4 (CXCR4) axis. METHODS: A rat model of VaD was established, and treated with QBT. Cognitive dysfunction in VaD rats was assessed using the Y-maze, new object recognition, and Morris water maze tests. Neuronal damage and inflammatory response in VaD rats were examined through Nissl staining, immunofluorescence, enzyme-linked immunospecific assay, and western blotting analysis. Furthermore, the effects of QBT on CXCL12/CXCR4 axis and its downstream signaling pathways, Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/nuclear factor-κB (NF-κB), were investigated in VaD rats and BV2 microglial cells exposed to oxygen glucose deprivation. RESULTS: QBT significantly alleviated cognitive dysfunction and neuronal damage in VaD rats, along with inhibition of VaD-induced over-activation of microglia and astrocytes and inflammatory response. Moreover, QBT exhibited anti-inflammatory effects by inhibiting the CXCL12/CXCR4 axis and its downstream JAK2/STAT3 and PI3K/AKT/NF-κB pathways, thereby attenuating the neuroinflammatory response both in vivo and in vitro. CONCLUSION: QBT effectively mitigated neuronal damage and cognitive dysfunction in VaD rats, exerting neuroprotective effects by suppressing neuroinflammatory response through inhibition of the CXCL12/CXCR4 axis.

Comparison of oral aprepitant and intravenous fosaprepitant for prevention of chemotherapy-induced nausea and vomiting in pediatric oncology patients: a randomized phase III trial.

Background: Neurokinin-1 receptor antagonists have improved the management of chemotherapy-induced nausea and vomiting (CINV), but to date there has been no prospective comparison between oral aprepitant and intravenous fosaprepitant in pediatric oncology patients. Methods: Our study was a double-parallel study, and the distribution ratio was 1:1. Children aged 2-12 years who were undergoing moderate or highly emetogenic chemotherapy (MEC or HEC) were randomly assigned to receive ondansetron and dexamethasone combined with either a single dose of intravenous fosaprepitant (arm A), or 3 days of oral aprepitant (arm B). The primary outcome measure was the rate of complete response (CR) of CINV within the acute phase, defined as from the start through 24 hours after the last chemotherapy dose. Response during the delayed phase, overall response, and use of rescue antiemetics were also assessed. Results: We prospectively evaluated 108 eligible patients, including 55 receiving fosaprepitant. Study observations were made during a single cycle for each patient. The occurrence of CR in the acute phase was statistically higher for patients receiving fosaprepitant (95% vs. 79%, P=0.018<0.05). Modest differences were seen in CR rates during the delayed phase (71% vs. 66%, P=0.586), and overall response rate (69% vs. 57%, P=0.179). The use of antiemetic rescue medicines was similar between arms A (11%) and B (7%). Conclusions: Fosaprepitant produced more CRs of CINV in the acute phase than did aprepitant, although there were no statistical differences in delayed phase response, overall response, or use of rescue antiemetics. This study confirms the safety, efficacy, and potential advantages of fosaprepitant in reducing CINV in pediatric oncology patients. Trial Registration: ClinicalTrials.gov identifier: NCT04873284.

A Randomized Comparison of Multimodal Analgesia and Fentanyl-Based Patient-Controlled Analgesia in Women Undergoing Robot-Assisted Bilateral Axillary Breast Approach Thyroidectomy.

Opioid-free multimodal analgesia (MMA) emerges as a preferable approach for postoperative pain management compared to opioid-based patient-controlled analgesia (PCA) in robot-assisted bilateral axillary breast approach thyroidectomy, a procedure commonly undergone by young female patients. We compared the analgesic efficacy and other recovery profiles between MMA and PCA. In total, 88 female patients were administered fentanyl-based PCA or the combination of lidocaine continuous infusion and nefopam injection before recovery from general anesthesia. The visual analog scale score of postoperative pain was assessed at the post-anesthesia care unit and at 6, 12, and 24 h after the termination of surgery. Postoperative nausea and vomiting (PONV), rescue analgesic and anti-emetic agents, recovery profiles, and adverse events were also compared. The median numeric rating scores on postoperative pain at 6 h after recovery from general anesthesia were three in both groups, with no significant difference between the groups at any time point. The PONV incidence was significantly higher in the PCA group than in the MMA group. The combination of systemic lidocaine infusion and nefopam injection has an analgesic effect equivalent to that of fentanyl-based PCA without PONV.

Effects of occupational exposure to dust, gas, vapor and fumes on chronic bronchitis and lung function.

Background: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality worldwide, and therefore the identification of the modifiable risk factors [such as exposure to vapors, gases, dust and fumes (VGDF)] for accelerate disease progression has important significance. Methods: We conducted COPD surveillance in six cities of southern China between 2014 and 2019. We recorded the diagnosis of chronic bronchitis, respiratory symptoms, occupational exposure to VGDF and other covariates by using a structured questionnaire. Logistic regression and multivariate linear regression model were adopted for analysis. We performed sensitivity analyses based on two methods of propensity score (PS) methods to evaluate the robustness of our results. Results: A total of 7,418 participants were included. Cough [odds ratios (ORs): 1.60, 95% confidence interval (CI): 1.22 to 2.08] and phlegm (OR: 1.49, 95% CI: 1.19 to 1.85) correlated significantly with exposure to dust. There was an increased risk of cough (OR: 1.53, 95% CI: 1.11 to 2.07) for occupational exposure to gas/vapor/fume. Dual exposure to dust and gas/vapor/fume was associated with a significantly increased risk of chronic bronchitis (OR: 1.74, 95% CI: 1.20 to 2.52), cough (OR: 1.43, 95% CI: 1.15 to 1.79) and phlegm (OR: 1.49, 95% CI: 1.24 to 1.79). In 5,249 participants with complete data of spirometry, gas/vapor/fume was associated with a decreased ratio of forced expiratory volume in one second and forced vital capacity (FEV1/FVC) (ß: -1.05, 95% CI: -1.85 to -0.26) and maximal mid-expiratory flow (MMEF) (ß: -0.15, 95% CI: -0.23 to -0.07). Dual exposure to dust and gas/vapor/fume was significantly associated with decreased FEV1/FVC (ß: -0.74, 95% CI: -1.28 to -0.20) and MMEF (ß: -0.06, 95% CI: -0.12 to -0.01). Results of sensitivity analysis were not materially changed. Conclusions: VGDF exposure is associated with chronic bronchitis, respiratory symptoms and decreased lung function, suggesting that VGDF contributes to the pathogenesis and progression of COPD.

Prevalence and risk factors of fatigue and its association with quality of life among patients with chronic pancreatitis: A cross-sectional study.

BACKGROUND: Fatigue is a debilitating symptom found in various chronic diseases and is associated with more severe symptoms and worse quality of life (QoL). However, this symptom has not been adequately addressed in chronic pancreatitis (CP), and there have been no studies on fatigue in patients with CP. METHODS: This cross-sectional study was conducted at the Changhai Hospital in Shanghai, China. Data on the patients' sociodemographic, disease, and therapeutic characteristics were collected. Fatigue was assessed using the Multidimensional Fatigue Inventory-20. QoL was assessed utilizing the European Organization for the Research and Treatment of Cancer of QoL questionnaire (EORTC-QLQ-C30). Sleep quality, anxiety and depression, and pain was assessed using Pittsburgh Sleep Quality Index, the Hospital Anxiety and Depression Scale, and the Brief Pain Inventory, respectively. RESULTS: The prevalence of fatigue among Chinese patients with CP was 35.51 % (87/245). Multivariate analysis showed that steatorrhea (OR = 2.638, 95 % CI: 1.117-6.234), history of smoking (OR = 4.627, 95 % CI: 1.202-17.802), history of endoscopic treatment (OR = 0.419, 95 % CI: 0.185-0.950), depression (OR = 5.924, 95 % CI: 2.462-14.255), and sleep disorder (OR = 6.184, 95 % CI: 2.543-15.034) were influencing factors for the presence of fatigue. The scores for global health and all functional dimensions in the EORTC-QLQ-C30 significantly decreased, whereas the scores for all symptom dimensions significantly increased in patients with fatigue. CONCLUSIONS: This study indicated that Fatigue is a common symptom and has a negative impact on the QoL of patients with CP. Steatorrhea, smoking history, endoscopic treatment, depression, and sleep disorders were associated with fatigue.

Morphologic and genomic changes of thyroid cancer cell lines exposed to conditions of simulated microgravity.

Microgravity in space impacts human health. In particular, thyroid cancer, which has a high incidence rate, has been the subject of numerous studies with respect to microgravity. However, most studies have focused on Western follicular thyroid cancer cell lines, while data regarding the effects of microgravity on Asian cell lines are lacking. Therefore, we aimed to investigate the effect of simulated ground-based microgravity on two Korean thyroid cancer cell lines, namely SNU-790 and SNU-80. We found that both cell lines formed multicellular spheroids under simulated microgravity. Gene expression analysis revealed that in SNU-790 cells, histone-related genes were upregulated and microRNA-related genes were downregulated. Meanwhile, in SNU-80 cells, genes related to the cellular response to hypoxia were downregulated. These findings contribute to a better understanding of the effects of microgravity on thyroid cancer cells. Further validation studies and clinical significance analyses are needed to fully understand the implications of these findings.

Intraoperative pathologic evaluation of central compartment lymph nodes in patients undergoing lobectomy for unilateral papillary thyroid carcinoma.

BACKGROUND/OBJECTIVE: Although papillary thyroid carcinoma (PTC) has an excellent prognosis, it can cause central lymph node metastasis (CLNM) which can increase local recurrence. Intraoperative pathologic evaluation (IOPE) can provide evidence regarding CLNM and help surgeons determine the appropriate surgical approach. The aim of this study was to evaluate the efficacy of IOPE and to determine risk factors associated with CLNM in unilateral PTC without preoperative clinical evidence of CLNM. METHODS: Medical charts of 227 patients who had unilateral PTC without clinical lymph node metastasis preoperatively were reviewed retrospectively. They were scheduled for thyroid lobectomy and prophylactic central lymphadenectomy (CND) from January 1, 2017 to December 31, 2017. RESULTS: Total follow-up period was 47.6 ± 10.6 months. CLNM was identified in 57 (25.1%) patients during IOPE and in 72 (31.7%) patients during final pathological analysis. The sensitivity and specificity of IOPE were 76.4% and 98.7%, respectively. IOPE through central lymph node dissection was safely performed with low complications (vocal cord palsy, 5.7%; hypoparathyroidism, 22.8%). Age < 55 years, echogenic foci on preoperative ultrasonography, and extrathyroidal extension at final pathological report were significantly associated with an increased risk of CLNM (p = 0.006, p < 0.001, and p < 0.001, respectively). In terms of oncological outcomes, there was no significant difference between the true negative and false negative results in IOPE. CONCLUSION: IOPE can safely provide accurate information for determining disease status and surgical extent. Further long-term studies are needed to evaluate clinical benefits of IOPE.

Virtual surgical planning in orthognathic surgery: a dental hospital's 10-year experience.

PURPOSE: The primary objective of this study was to evaluate how the utilization of virtual surgical planning (VSP) and the epidemiological profile of patients undergoing orthognathic surgery (OGS) have changed in the past decade. METHODS: The records of patients who had undergone orthognathic surgery at a national dental hospital were reviewed. Trends in VSP, epidemiological data, presentation of dentofacial deformity, and management details were recorded. RESULTS: A total of 1184 patients were included in this study. The majority of the patients seeking treatment in this dental hospital were young Chinese adults with dentofacial deformities requiring bimaxillary surgeries. Most patients presented with a skeletal Class III pattern (79.0%), and asymmetry was diagnosed in 80.8% of all cases. CONCLUSION: There was an initial slow pick-up rate for VSP, but this rapidly increased to a high adoption rate of 98.7-100% between 2019 and 2021. Together with an increasing body of evidence suggesting greater accuracy in VSP, utilization in this technology can be enhanced with greater familiarity with the technology and improvements in the VSP services.

N6-Methyladenosine (m6A) Modification in Natural Immune Cell-Mediated Inflammatory Diseases.

The post-transcriptional N6-methyladenosine (m6A) modification of RNA influences stability, transport, and translation with implications for various physiological and pathological processes. Immune cell development, differentiation, and activation are also thought to be regulated by m6A and affect host defense against pathogens and inflammatory response with impacts on infectious, neoplastic, autoimmune, cardiovascular, hepatic, and osteal diseases. The current review summarizes recent research on m6A in monocyte/macrophages, neutrophils, dendritic cells, natural killer cells, and microglia and gives insights into epigenetic modifications of the immune system and novel therapeutic strategies for immune-related diseases.

Comparative analysis between ultrasonic shears versus advanced bipolar device in transoral endoscopic thyroidectomy: a randomized controlled trial.

Background: The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is the most recently developed minimally invasive technique with no skin incision. For tissue dissection and bleeding control, the use of proper energy devices is very important in endoscopic thyroid surgery. To date, there have been no clinical studies reported regarding which energy device is better in TOETVA, ultrasonic shears or advanced bipolar device. The aim of our study is to determine which energy device is more useful for TOETVA. Methods: This study was designed as an open-label, prospective randomized controlled trial in a single university hospital. Patients were randomly assigned to the ultrasonic group or advanced bipolar group before the surgery. From June 2020 to May 2022, 40 patients were enrolled (20 patients were assigned to the ultrasonic group, and 20 patients were assigned to the advanced bipolar group). Primary endpoints were operation time for lobectomy, number of camera cleanings, and blood loss during the lobectomy. Secondary endpoints were pain score, postoperative drainage, and blood chemistry. A single endocrine surgeon had performed all surgeries. Results: There were no significant differences between the two groups in age, sex, body mass index (BMI), tumor location, preoperative cytology, or surgical extent. The time for lobectomy was significantly shorter in the advanced bipolar group (33.8±6.4 vs. 41.9±9.0 minutes, P=0.002). The number of camera cleanings was significantly lower in the advanced bipolar group (2.9±1.6 vs. 5.8±2.5 times, P<0.001). Estimated blood loss was also significantly less in the advanced bipolar group (11.5±17.3 vs. 81.8±99.5 mL, P=0.004). Postoperative hospital stays, drainage, pain score, laboratory findings, and complications were not significantly different between the two groups. Conclusions: According to this study, advanced bipolar device showed better performance, with a shorter operation time, less camera cleaning, and less blood loss. We suggest that advanced bipolar device can be a better choice in TOETVA. Trial Registration: ClinicalTrials.gov identifier: NCT04320901.

Cost-effectiveness analysis of dinutuximab ß for the treatment of high-risk neuroblastoma in China.

BACKGROUND: Dinutuximab ß can be used to treat children with high-risk neuroblastoma (NB). Due to its high price, whether dinutuximab ß is cost-effective for the treatment of high-risk NB remains uncertain. Therefore, assessing the cost-effectiveness of dinutuximab ß in children with high-risk NB is of high importance. METHODS: The health utilities and economic outcomes in children with high-risk NB were projected using a partitioned survival model. The individual patient data (IPD) of add-on treatment with dinutuximab ß (GD2 group) were derived from the literature, while the IPD of traditional therapy (TT group) were obtained from retrospective data of Shanghai Children's Medical Center. Treatment costs included drugs, adverse event-related expenses, and medical resource use. Utility values were obtained from the literature. Costs and quality-adjusted life-years (QALYs) were measured over a 10-year time horizon. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were also conducted. RESULTS: Compared with the TT group, QALY increased in the GD2 group by 0.72 with an increased cost of $171,269.70, leading to an incremental cost-effectiveness ratio of 236,462.75$/QALY. DSA showed that the price of dinutuximab ß was the main factor on the results than other parameters. Compared with the TT group, the GD2 group could not be cost-effective in the PSA at the $37,920/QALY threshold. CONCLUSION: Results found that dinutuximab ß is not a cost-effective treatment option for children with high-risk NB unless its price is significantly reduced.

Robot-Assisted Parathyroidectomy Using Indocyanine Green (ICG) Fluorescence in Primary Hyperparathyroidism.

Background and Objectives: Surgical treatment for primary hyperparathyroidism (PHPT) has evolved from bilateral exploration through a long transcervical incision to focused parathyroidectomy with a minimal incision above the pathologic gland. Recently, endoscopic or robot-assisted parathyroid surgery without direct neck incision has been introduced. The aim of this study was to investigate the effectiveness of indocyanine green (ICG) fluorescence as a new method for the visual identification of abnormal hyperfunctioning parathyroid glands in robot-assisted parathyroidectomy using FireflyTM technology. We also aimed to conduct a comparative analysis between robot-assisted parathyroidectomy and conventional focused parathyroidectomy in order to identify clinical differences between the two surgical approaches. Materials and Methods: A total of 37 patients with PHPT underwent parathyroidectomy at a single university hospital between September 2018 and December 2022. Thirty-one patients underwent open focused parathyroidectomy (open group), and six patients underwent robot-assisted parathyroidectomy (robot group). Pre-operative localization via parathyroid SPECT-CT and an intraoperative parathyroid hormone (IOPTH) assay were used to successfully remove the pathologic parathyroid in both groups. ICG was administered only in the robot group. Results: Pathologic parathyroid showed a persistent fluorescence pattern under near-infrared vision. After the removal of the fluorescent parathyroid gland, IOPTH was normalized in all six patients in the robot group. However, the open group showed shorter hospital stays (1.8 ± 1.2 vs. 3.0 ± 0.0 days, p < 0.001) and shorter operation times (91.1 ± 69.1 vs. 152.5 ± 23.6 min, p = 0.001) than the robot group. After 6 months of surgery, PTH, calcium, and ionized calcium levels were all normalized without significant differences between the groups. Conclusions: Robot-assisted parathyroidectomy using ICG is helpful for the visual identification of the pathologic parathyroid gland. The advantage of robot parathyroidectomy is a better cosmetic outcome. However, it still does not show better clinical outcomes than conventional open focused parathyroidectomy.

FOXK2 amplification and overexpression promotes breast cancer development and chemoresistance.

Activation of oncogenes through DNA amplification/overexpression plays an important role in cancer initiation and progression. Chromosome 17 has many cancer-associated genetic anomalies. This cytogenetic anomaly is strongly associated with poor prognosis of breast cancer. FOXK2 gene is located on 17q25 and encodes a transcriptional factor with a forkhead DNA binding domain. By integrative analysis of public genomic datasets of breast cancers, we found that FOXK2 is frequently amplified and overexpressed in breast cancers. FOXK2 overexpression in breast cancer patients is associated with poor overall survival. FOXK2 knockdown significantly inhibits cell proliferation, invasion and metastasis, and anchorage-independent growth, as well as causes G0/G1 cell cycle arrest in breast cancer cells. Moreover, inhibition of FOXK2 expression sensitizes breast cancer cells to frontline anti-tumor chemotherapies. More importantly, co-overexpression of FOXK2 and PI3KCA with oncogenic mutations (E545K or H1047R) induces cellular transformation in non-tumorigenic MCF10A cells, suggesting that FOXK2 is an oncogene in breast cancer and is involved in PI3KCA-driven tumorigenesis. Our study identified CCNE2, PDK1, and Estrogen receptor alpha (ESR1) as direct transcriptional targets of FOXK2 in MCF-7 cells. Blocking CCNE2- and PDK1-mediated signaling by using small molecule inhibitors has synergistic anti-tumor effects in breast cancer cells. Furthermore, FOXK2 inhibition by gene knockdown or inhibitors for its transcriptional targets (CCNE2 and PDK1) in combination with PI3KCA inhibitor, Alpelisib, showed synergistic anti-tumor effects on breast cancer cells with PI3KCA oncogenic mutations. In summary, we provide compelling evidence that FOXK2 plays an oncogenic role in breast tumorigenesis and targeting FOXK2-mediated pathways may be a potential therapeutic strategy in breast cancer.

Thrap3 promotes nonalcoholic fatty liver disease by suppressing AMPK-mediated autophagy.

Autophagy functions in cellular quality control and metabolic regulation. Dysregulation of autophagy is one of the major pathogenic factors contributing to the progression of nonalcoholic fatty liver disease (NAFLD). Autophagy is involved in the breakdown of intracellular lipids and the maintenance of healthy mitochondria in NAFLD. However, the mechanisms underlying autophagy dysregulation in NAFLD remain unclear. Here, we demonstrate that the hepatic expression level of Thrap3 was significantly increased in NAFLD conditions. Liver-specific Thrap3 knockout improved lipid accumulation and metabolic properties in a high-fat diet (HFD)-induced NAFLD model. Furthermore, Thrap3 deficiency enhanced autophagy and mitochondrial function. Interestingly, Thrap3 knockout increased the cytosolic translocation of AMPK from the nucleus and enhanced its activation through physical interaction. The translocation of AMPK was regulated by direct binding with AMPK and the C-terminal domain of Thrap3. Our results indicate a role for Thrap3 in NAFLD progression and suggest that Thrap3 is a potential target for NAFLD treatment.

Ocular surface complications following biological therapy for cancer.

Novel and highly effective biological agents developed to treat cancer over the past two decades have also been linked to multiple adverse outcomes, including unanticipated consequences for the cornea. This review provides an overview of adverse corneal complications of biological agents currently in use for the treatment of cancer. Epidermal growth factor receptor inhibitors and immune checkpoint inhibitors are the two classes of biological agents most frequently associated with corneal adverse events. Dry eye, Stevens-Johnson syndrome, and corneal transplant rejection have all been reported following the use of immune checkpoint inhibitors. The management of these adverse events requires close collaboration between ophthalmologists, dermatologists, and oncologists. This review focuses in depth on the epidemiology, pathophysiology, and management of ocular surface complications of biological therapies against cancer.

First Experience of Single-Port Robotic Areolar Approach Thyroidectomy.

OBJECTIVES: Numerous minimally invasive thyroidectomy techniques have been developed and are actively utilized in hospitals around the globe. Herein, we describe a recently developed minimally invasive thyroidectomy technique that employs the da Vinci SP, and we present the preliminary clinical outcomes of single-port robotic areolar thyroidectomy (SPRA). METHODS: A 3-cm semi-circular incision on the right areola and a small 8-mm incision on the left areola were created. Using hydro-dissection and an advanced bipolar device, a subcutaneous skin flap was created, extending from the areola to the thyroid cartilage. The da Vinci SP was then inserted through the incision in the right areola. Between December 2022 and March 2023, 21 SPRA procedures were conducted. Patients' medical records and surgical videos were subsequently reviewed. RESULTS: Lobectomy was performed in 17 patients, isthmectomy in 2 patients, and total thyroidectomy in 2 patients. The mean flap time was 14.9±4.2 minutes and the console time was 62.4±17.1 minutes. The mean tumor size was 0.89± 0.65 cm and the number of retrieved lymph nodes was 3.94±3.98 (range, 0-12). There were no observed instances of vocal cord palsy or hypoparathyroidism. CONCLUSION: We successfully developed and performed the novel SPRA for the first time worldwide. Unlike other robotic surgery. METHODS: SPRA is less invasive and leaves no visible scars. This technique employs a sophisticated single-port robotic device. However, to assess the efficacy of this method, we need to analyze more cases and conduct comparative studies in the near future.

Evaluation of the potential herb-drug interaction between Bojungikki-tang and PD-L1 immunotherapy in a syngeneic mouse model.

Atezolizumab (a PD-L1 inhibitor) has shown remarkable efficacy and tolerability in various cancer types. Despite its efficacy and safety, atezolizumab monotherapy has limitations, such as acquired resistance and adverse events. Bojungikki-tang (BJIKT) is an herbal decoction widely prescribed in Asian countries and used to treat cancer-related symptoms including fatigue, appetite loss, gastrointestinal disorders, and other side effects from cancer therapy. Due to its immunomodulatory effects, Bojungikki-tang has been investigated as a combined treatment with anticancer agents. We evaluated the potential drug-drug interaction (DDI) between Bojungikki-tang and the anti-PD-L1 antibody based on the Food and Drug Administration (FDA) guidelines. In the study, we conducted an in vivo drug-drug interaction study using a syngeneic mouse model of CMT-167 in C57BL/6. We then determined the antibody concentrations to evaluate the pharmacokinetic (PK) drug-drug interaction and measured variable biomarkers related to therapeutic efficacy and immune response. The pharmacodynamic (PD) drug-drug interaction study investigated changes in response between anti-PD-L1 antibody monotherapy and combination therapy. Using the pharmacokinetic and pharmacodynamic data, we conducted a statistical analysis to assess drug-drug interaction potential. In the presence of Bojungikki-tang, the pharmacokinetic characteristics of the anti-PD-L1 antibody were not changed. This study suggested that combination treatment with Bojungikki-tang and atezolizumab is a safe treatment option for non-small cell lung cancer. Clinical studies are warranted to confirm this finding.