Explore the vast range of titles available.

A large number of studies have focused on the role of substance P (SP) and the neurokinin-1 receptor (NK1R) in the pathogenesis of a variety of medical conditions. This review provides an overview of the role of the SP-NK1R pathway in the pathogenesis of musculoskeletal disorders and the evidence for its role as a therapeutic target for these disorders, which are major public health problems in most countries. To summarize, the brief involvement of SP may affect tendon healing in an acute injury setting. SP combined with an adequate conjugate can be a regenerative therapeutic option in osteoarthritis. The NK1R antagonist is a promising agent for tendinopathy, rheumatoid arthritis, and osteoarthritis. Research on the SP-NK1R pathway will be helpful for developing novel drugs for osteoporosis.

Defining the functional modules within transcriptional regulatory factors that govern switching between repression and activation events is a central issue in biology. Recently, we have reported the dynamic role of a β-catenin–reptin chromatin remodelling complex in regulating a metastasis suppressor gene KAI1 (ref. 1 ), which is capable of inhibiting the progression of tumour metastasis 2 , 3 , 4 , 5 . Here, we identify signalling factors that confer repressive function on reptin and hence repress the expression of KAI1 . Biochemical purification of a reptin-containing complex has revealed the presence of specific desumoylating enzymes that reverse the sumoylation of reptin that underlies its function as a repressor. Desumoylation of reptin alters the repressive function of reptin and its association with HDAC1. Furthermore, the sumoylation status of reptin modulates the invasive activity of cancer cells with metastatic potential. These data clearly define a functional model and provide a novel link for SUMO modification in cancer metastasis.

Background: This study aims to verify whether the blood flow velocity and the diameter size, measured through intra-carotid artery Doppler measurements performed on sepsis patients visiting the emergency department, are useful as tools for predicting the risk of early death. Methods: As a prospective study, this research was performed on sepsis patients who visited a local emergency medical center from August 2021 to February 2023. The sepsis patients’ carotid artery was measured using Doppler imaging, and they were divided into patients measured for the size of systolic and diastolic mean blood flow velocity and diameter size: those measured for their qSOFA (quick sequential organ failure assessment) score and those measured using the SIRS (systemic inflammatory response syndrome) criteria. By measuring and comparing their mortality prediction accuracies, this study sought to verify the usefulness of blood flow velocity and the diameter size of the intra-carotid artery as tools to predict early death. Results: This study was conducted on 1026 patients, excluding 45 patients out of the total of 1071 patients. All sepsis patients were measured using systolic and diastolic blood flow velocity and diameter by Doppler imaging of the intra-carotid artery, assessed using qSOFA and evaluated using SIRS criteria. The results of the analysis performed to compare the mortality prediction accuracy were as follows. First, the hazard ratio (95% CI) of the intra-carotid artery was significant (p < 0.05), at 1.020 (1.004–1.036); the hazard ratio (95% CI) of qSOFA was significant (p < 0.05), at 3.871 (2.526–5.931); and the hazard ratio (95% CI) of SIRS showed no significant difference, at 1.002 (0.995–1.009). After 2 h of infusion treatment, the diameter size was 4.72 ± 1.23, showing a significant difference (p < 0.05). After 2 h of fluid treatment, the blood flow velocity was 101 m/s ± 21.12, which showed a significant difference (p < 0.05). Conclusions: Measuring the mean blood flow velocity in the intra-carotid arteries of sepsis patients who visit the emergency department is useful for predicting the risk of death at an early stage. And this study showed that Doppler measurement of the diameter size of the carotid artery significantly increased after performing fluid treatment after early recognition.

Early detection and classification of bone tumors in the proximal femur is crucial for their successful treatment. This study aimed to develop an artificial intelligence (AI) model to classify bone tumors in the proximal femur on plain radiographs. Standard anteroposterior hip radiographs were obtained from a single tertiary referral center. A total of 538 femoral images were set for the AI model training, including 94 with malignant, 120 with benign, and 324 without tumors. The image data were pre-processed to be optimized for training of the deep learning model. The state-of-the-art convolutional neural network (CNN) algorithms were applied to pre-processed images to perform three-label classification (benign, malignant, or no tumor) on each femur. The performance of the CNN model was verified using fivefold cross-validation and was compared against that of four human doctors. The area under the receiver operating characteristic (AUROC) of the best performing CNN model for the three-label classification was 0.953 (95% confidence interval, 0.926-0.980). The diagnostic accuracy of the model (0.853) was significantly higher than that of the four doctors (0.794) (P = 0.001) and also that of each doctor individually (0.811, 0.796, 0.757, and 0.814, respectively) (P<0.05). The mean sensitivity, specificity, precision, and F1 score of the CNN models were 0.822, 0.912, 0.829, and 0.822, respectively, whereas the mean values of four doctors were 0.751, 0.889, 0.762, and 0.797, respectively. The AI-based model demonstrated high performance in classifying the presence of bone tumors in the proximal femur on plain radiographs. Our findings suggest that AI-based technology can potentially reduce the misdiagnosis of doctors who are not specialists in musculoskeletal oncology.

Posttranslational modification by small ubiquitin-like modifier (SUMO) controls diverse cellular functions of transcription factors and coregulators and participates in various cellular processes including signal transduction and transcriptional regulation. Here, we report that pontin, a component of chromatin-remodeling complexes, is SUMO-modified, and that SUMOylation of pontin is an active control mechanism for the transcriptional regulation of pontin on androgen-receptor target genes in prostate cancer cells. Biochemical purification of pontin-containing complexes revealed the presence of the Ubc9 SUMO-conjugating enzyme that underlies its function as an activator. Intriguingly, 5α-dihydroxytestosterone treatments significantly increased the SUMOylation of pontin, and SUMOylated pontin showed further activation of a subset of nuclear receptor-dependent transcription and led to an increase in proliferation and growth of prostate cancer cells. These data clearly define a functional model and provide a link between SUMO modification and prostate cancer progression.

Intractable xerostomia is defined as the subjective perception of dry mouth and persistent salivary gland hypofunction. Pilocarpine is an approved salivary sialagogue that is frequently prescribed for the treatment of intractable xerostomia; however, it often exhibits more side effects at high-doses and limited effectiveness at low-doses. Baekhogainsam-Tang (BIT) is a common herbal formula used by patients complaining of sore throats and thirst. It seems that BIT can compensate for the insufficient effect of low-dose pilocarpine. However, no clinical trials have studied the efficacy of combined administration of BIT and low-dose pilocarpine for intractable xerostomia. We aim to assess the non-inferior efficacy and fewer side effects of combined administration of BIT and low-dose pilocarpine compared with the administration of high-dose pilocarpine. A randomized, open-label, parallel-group, multi-center trial will be conducted. A total of 120 patients with Sjogren's syndrome having an unstimulated salivary flow rate (SFR) ≤0.1 mL/min or who have undergone radiotherapy to the head and neck with an unstimulated SFR ≤0.25 mL/min will be recruited competitively. They will be randomly allocated to either the experimental or control groups. The experimental group will receive BIT herbal granules three times and pilocarpine (2.5-mg) four times daily; meanwhile, the control group will receive only 5-mg pilocarpine four times daily for 12 weeks. The primary outcome is unstimulated SFR after 12 weeks of treatment. Secondary outcomes are stimulated SFR after 12 weeks of medication, as well as differences and mean percentage changes in unstimulated and stimulated SFR, visual analog scale, salivary scintigraphy, and questionnaires for both oral symptoms and quality of life during the clinical trial. An independent T test or Mann-Whitney U test will be performed to compare values between the two groups. The Paired T test or Wilcoxon signed-rank test will be performed to compare intragroup continuous values. This trial will be significant evidence on the efficacy and safety of combined use of BIT and low-dose pilocarpine to treat intractable xerostomia. The Clinical Research Information Service of the Republic of Korea (ISRCTN, KCT0005982). Registered on 10 February 2021.

Purpose This study aimed to evaluate the outcomes of arthroscopic type 2 superior labrum anterior–posterior (SLAP) lesion repair in the general population and compare clinical outcomes according to patient age and repair site. Methods Between 2005 and 2018, patients who underwent arthroscopic repair for isolated type 2 SLAP lesions were retrospectively reviewed. Baseline characteristics, pre- and postoperative [1-year and > 2-year (final)] shoulder range-of-motion, and functional scores, comprising the pain visual analogue scale (PVAS), functional VAS, and American Shoulder and Elbow Surgeons (ASES) score, were evaluated. Return to overhead activities and subjective satisfaction were assessed at the final follow-up, and patients were divided by age [group YB (< 40 years] and group OB (≥ 40 years)] and repair site [group P (only posterior labrum repair) and group AP (anterior and posterior labrum repair)]. Overall patient outcomes were analysed and compared between groups. Results This study included 54 patients (45 men) with a mean age of 37.1 ± 8.3 years. The mean follow-up was 90.8 ± 51.3 months. Two patients experienced early failure, and one patient had a ruptured biceps tendon during the follow-up period. Final functional scores improved compared to their preoperative scores in all patients, except three (all p  < 0.001). Fifty patients (98.0%) were satisfied, and 39 patients (76.5%) were able to perform overhead sports without restriction. In 25 patients who attended more than 7 years of follow-up (mean, 11.3 ± 2.7 years), 21 patients (84%) had an ASES score ≥ 80, and all patients had PVAS ≤ 2. There was no significant difference in clinical outcomes between groups YB and OB. The final median external rotation was significantly more restricted in group AP than in group P (40 [25–65] vs. 60 [50–70], p  = 0.002). Conclusion Arthroscopic type 2 SLAP repair induced good short- and long-term clinical outcomes, return to overhead activities, and subjective satisfaction in the general population, regardless of age, due to the careful evaluation of patient history, physical examination, and imaging studies. However, performing only posterior repair seems sufficient since anterior labral SLAP lesion repair can limit ER. Isolated type 2 SLAP lesion posterior repair only is, thus, recommended to reduce external rotation deficit risk and increase satisfaction, regardless of patient age. Study design Case series. Level of evidence Level IV.

Background Various cancer stem cell (CSC) biomarkers and the genes encoding them in head and neck squamous cell carcinoma (HNSCC) have been identified and evaluated. However, the validity of these factors in the prognosis of HNSCC has been questioned and remains unclear. In this study, we examined the clinical significance of CSC biomarker genes in HNSCC, using five publicly available HNSCC cohorts. Methods To predict the prognosis of patients with HNSCC, we developed and validated the expression signatures of CSC biomarker genes whose mRNA expression levels correlated with at least one of the four CSC genes ( CD44 , MET , ALDH1A1 , and BMI1 ). Results Patients in The Cancer Genome Atlas (TCGA) HNSCC cohort were classified into CSC gene expression-associated high-risk (CSC-HR; n  = 285) and CSC gene expression-associated low-risk (CSC-LR; n  = 281) subgroups. The 5-year overall survival and recurrence-free survival rates were significantly lower in the CSC-HR subgroup than in the CSC-LR subgroup ( p  = 0.04 and 0.02, respectively). The clinical significance of the CSC gene expression signature was validated using four independent cohorts. Analysis using Cox proportional hazards models showed that the CSC gene expression signature was an independent prognostic factor of non-oropharyngeal HNSCC which mostly indicates HPV (–) status. Furthermore, the CSC gene expression signature was associated with the prognosis of HNSCC patients who received radiotherapy. Conclusion The CSC gene expression signature is associated with the prognosis of HNSCC and may help in personalized treatments for patients with HNSCC, especially in cases with HPV (–) status who were classified in more detail.

To enhance the efficacy of radiotherapy (RT) in human papillomavirus (HPV)‐negative head and neck squamous cell carcinoma (HNSCC), we explored targeting ferroptosis, a regulated cell death process. We developed a gene signature associated with ferroptosis using Cox proportional hazard modeling in HPV‐negative HNSCC patients who underwent RT. This ferroptosis‐related gene signature (FRGS) was a significant predictor of overall survival and recurrence‐free survival in HPV‐negative HNSCC patients who received RT. Subtype B of the FRGS, characterized by decreased expression of ferroptosis inducers [nuclear receptor coactivator 4 (NCOA4) and natural resistance‐associated macrophage protein 2 homolog/divalent metal transporter 1 (NRAMP2/DMT1)] and increased expression of suppressors [phospholipid hydroperoxide glutathione peroxidase (GPX4) and ferritin heavy chain (FTH1)], was associated with poorer prognosis, potentially indicating the inhibition of ferroptosis. Furthermore, our in vitro and in vivo studies demonstrated that treatment with statins, such as atorvastatin and simvastatin, induced ferroptosis and sensitized radioresistant HNSCC cells to irradiation, improving radiosensitivity and potentially enhancing the response to RT. Additionally, in xenograft models, the combination of statins and RT led to a significant reduction in tumor initiation. These findings provide valuable insights for enhancing treatment and improving prognosis in HPV‐negative HNSCC by targeting ferroptosis and utilizing statins to sensitize tumors to RT‐induced cell death. Radiosensitive head and neck squamous cell carcinoma (HNSCC) cells downregulate GPX4 expression upon ionizing radiation (IR) exposure, inducing ferroptosis, whereas radioresistant HNSCC cells fail to do so. However, the combination of IR and statins can downregulate GPX4 expression, thereby inducing ferroptosis in radioresistant HNSCC cells as well.