Increased FGFR3 is involved in T-2 toxin-induced lesions of hypertrophic cartilage associated with endemic osteoarthritis.

This study evaluated the effect of fibroblast growth factor receptor 3 (FGFR3) on damaged hypertrophic chondrocytes of Kashin-Beck disease (KBD). Immunohistochemical staining was used to evaluate FGFR3 expression in growth plates from KBD rat models and engineered cartilage. In vitro study, hypertrophic chondrocytes were pretreated by FGFR3 binding inhibitor (BGJ398) for 24 h before incubation at different T-2 toxin concentrations. Differentiation -related genes (Runx2, Sox9, and Col Ⅹ) and ECM degradation -related genes (MMP-13, Col Ⅱ) in the hypertrophic chondrocytes were analyzed using RT-PCR, and the corresponding proteins were analyzed using western blotting. Hypertrophic chondrocytes death was detected by the Annexin V/PI double staining assay. The integrated optical density of FGFR3 staining was increased in knee cartilage of rats and engineered cartilage treated with T-2 toxin. Both protein and mRNA levels of Runx2, Sox9, Col Ⅱ, and Col Ⅹ were decreased in a dose-dependent manner when exposed to the T-2 toxin and significantly upregulated by 1 µM BGJ398. The expression of MMP-1, MMP-9, and MMP-13 increased in a dose-dependent manner when exposed to T-2 toxin and significantly reduced by 1 µM BGJ398. 1 µM BGJ398 could prevent early apoptosis and necrosis induced by the T-2 toxin. Inhibiting the FGFR3 signal could alleviate extracellular matrix degradation, abnormal chondrocytes differentiation, and excessive cell death in T-2 toxin-induced hypertrophic chondrocytes.

Highly Biocompatible Polyester-Based Piezoelectric Elastomer with Antitumor and Antibacterial Activity for Ultrasound-Enhanced Piezoelectric Therapy.

Currently, the use of piezoelectric materials to provide sustainable and noninvasive bioelectric stimulation to eradicate tumor cells and accelerate wound healing has raised wide attention. The development of a multifunctional piezoelectric elastomer with the ability to perform in situ tumor therapy as well as wound repair is of paramount importance. However, current piezoelectric materials have a large elastic modulus and limited stretchability, making it difficult to match with the dynamic curvature changes of the wound. Therefore, by copolymerizing lactic acid, butanediol, sebacic acid, and itaconic acid to develop a piezoelectric elastomer (PLBSIE), we construct a new ultrasound-activated PLBSIE-based tumor/wound unified therapeutic platform. Excitedly, it showed outstanding piezoelectric performance and high stretchability, and the separated carrier could react with water to generate highly cytotoxic reactive oxygen species (ROS), contributing to effectively killing tumor cells and eliminating bacteria through piezoelectric therapy. In addition, ultrasound-triggered piezoelectric effects could promote the migration and differentiation of wound-healing-related cells, thus accelerating wound healing. Herein, such a piezoelectric elastomer exerted a critical role in postoperative tumor-induced wound therapy and healing with the merits of possessing multifunctional abilities. Taken together, the developed ultrasound-activated PLBSIE will offer a comprehensive treatment for postoperative osteosarcoma therapy.

Melatonin Improves Mitochondrial Dysfunction and Attenuates Neuropathic Pain by Regulating SIRT1 in Dorsal Root Ganglions.

Neuropathic pain is a debilitating chronic pain condition and is refractory to the currently available treatments. Emerging evidence suggests that melatonin exerts analgesic effects in rodent models of neuropathic pain. Nevertheless, the exact underlying mechanisms of the analgesic effects of melatonin on neuropathic pain are largely unknown. Here, we observed that spinal nerve ligation (SNL) in rats L5 and L6 induced an obvious decrease in the 50% paw withdrawal threshold (PWT) and paw withdrawal latency (PWL), indicating the induction of mechanical allodynia and the hyperalgesia, and melatonin prevented the genesis and maintenance of mechanical allodynia and the hyperalgesia. Notably, the inhibitory action of melatonin on SNL-induced mechanical allodynia and heat hypersensitivity was inhibited by a SIRT1 inhibitor (EX527). Melatonin treatment increased the expression of neuronal sirtuin1 (SIRT1) in DRGs following nerve injury. Furthermore, melatonin treatment restored the injury-dependent decrease in mitochondrial membrane potential and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and reduced the injury-dependent increase in hydrogen peroxide and 8-hydroxy-2-deoxyguanosine (8-OHdG), which was inhibited by EX527. In addition, we found that EX527 impeded the inhibitory effects of melatonin on the SNL-induced increased expression of cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). In conclusion, the above data demonstrated that melatonin alleviated mechanical allodynia and hyperalgesia induced by peripheral nerve injury via SIRT1 activation. Melatonin resolved mitochondrial dysfunction-oxidative stress-dependent and neuroinflammation mechanisms that were driven by SIRT1 after nerve injury.

Change in quality of life and return to work and sports after isolated closing-wedge distal femoral osteotomy.

PURPOSE: To analyze return to work and sports, and health-related quality of life (HRQoL) after closing-wedge distal femoral osteotomy (CWDFO) for valgus deformity and lateral compartmental osteoarthritis. METHODS: Thirty-three patients underwent isolated CWDFO in our center between January 2018 and June 2020 were enrolled, of whom 32 and 23 patients were included in the return-to-work and return-to-sports analyses, respectively. Short Form-36 (SF-36), Tegner score, Knee injury and Osteoarthritis Outcome Score (KOOS) and visual analog scale (VAS) pain score were compared preoperatively and postoperatively. And postoperative complications were recorded. RESULTS: Overall, 33 patients were contacted at a mean follow-up of 37.94 ± 6.68 months, with a median age of 35 years (range: 26-63 years) at the surgery time. The physical component summary of SF-36 (p < 0.001) increased significantly at 1 year postoperatively. All patients returned to work, including 96.86% who returned to the same level of work in 1.89 ± 0.98 months, and to sports, including 78.26% who returned to the same sport level in 6.50 ± 2.05 months. Rates of returning to work (p = 0.215) and sports (p = 0.165) did not differ with work/sports intensity. Tegner scores (p = 0.025) and VAS pain scores (p < 0.001) decreased, and KOOS (p < 0.001) increased at 1 year postoperatively. Revision/conversion surgery was not required. In all, 30.43% patients reported a subjective decrease in sports ability; 82.61% patients considered their sports ability acceptable. CONCLUSION: Patients returned to work/sports after isolated CWDFO, and had increased HRQoL. Patients playing high-impact sports had lower rates of returning to the same sport level, and may require preoperative counseling. LEVEL OF EVIDENCE: IV, Case series.

The PFNA in treatment of intertrochanteric fractures with or without lateral wall fracture in elderly patients: a retrospective cohort study.

BACKGROUND: There is no consensus about intertrochanteric fractures with lateral wall treated with intramedullary nail-proximal femoral nail antirotation (PFNA). The aim of the present study was to compare function outcomes between lateral wall and no lateral wall fractures after surgery by PFNA. METHODS: This retrospective study evaluated patients with or without lateral wall fractures who underwent PFNA between January 2015 and June 2018. The operative time, intraoperative blood loss, time to fracture healing, complications and functional outcomes qualified by Harris hip score and Parker - Palmer mobility score (PPMS) were compared between the two groups. RESULTS: Two groups were comparable with regard to patient age, sexual distribution, mechanism of injury, fracture type, body mass index (BMI), Time to surgery, American Society of Anesthesiologists (ASA) score and quality of reduction. The incomplete group had a longer operation time (54.1 ± 8.74 min vs. 51.0 ± 9.86 min) and more intraoperative blood loss (228.4 ± 48.8 ml vs. 151.3 ± 43.5 ml) in comparison with the control group (P < 0.01). Regarding functional outcome, the HHSs of the two groups were 76.2 ± 11.6 vs 75.6 ± 12.5 at the 3 months (P = 0.603), 81.9 ± 9.4 vs 82.6 ± 8.7 at the six months (P = 0.224), 83.8 ± 6.6 vs 84.5 ± 6.0 at the twelve months 85.2 ± 5.5 vs 86.0 ± 5.8 at the twenty-four months (P > 0.05), respectively. Similar results were obtained about PPMS. We found no difference in Weight bearing time, Time of fracture healing, and Complications between incomplete group and intact group. CONCLUSIONS: There is no substantial difference in functional results or complication rates for intertrochanteric fractures with lateral wall fractures, except from increased blood loss and operation time. We believe that an intramedullary nail will be sufficient to repair an intertrochanteric fracture with or without a lateral wall fracture.

A novel NET-related gene signature for predicting DLBCL prognosis.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy. Neutrophil extracellular traps (NETs) are pathogen-trapping structures in the tumor microenvironment that affect DLBCL progression. However, the predictive function of NET-related genes (NRGs) in DLBCL has received little attention. This study aimed to investigate the interaction between NRGs and the prognosis of DLBCL as well as their possible association with the immunological microenvironment. METHODS: The gene expression and clinical data of patients with DLBCL were downloaded from the Gene Expression Omnibus database. We identified 148 NRGs through the manual collection of literature. GSE10846 (n = 400, GPL570) was used as the training dataset and divided into training and testing sets in a 7:3 ratio. Univariate Cox regression analysis was used to identify overall survival (OS)-related NETs, and the least absolute shrinkage and selection operator was used to evaluate the predictive efficacy of the NRGs. Kaplan-Meier plots were used to visualize survival functions. Receiver operating characteristic (ROC) curves were used to assess the prognostic predictive ability of NRG-based features. A nomogram containing the clinical information and prognostic scores of the patients was constructed using multivariate logistic regression and Cox proportional risk regression models. RESULTS: We identified 36 NRGs that significantly affected patient overall survival (OS). Eight NRGs (PARVB, LYZ, PPARGC1A, HIF1A, SPP1, CDH1, S100A9, and CXCL2) were found to have excellent predictive potential for patient survival. For the 1-, 3-, and 5-year survival rates, the obtained areas under the receiver operating characteristic curve values were 0.8, 0.82, and 0.79, respectively. In the training set, patients in the high NRG risk group presented a poorer prognosis (p < 0.0001), which was validated using two external datasets (GSE11318 and GSE34171). The calibration curves of the nomogram showed that it had excellent predictive ability. Moreover, in vitro quantitative real-time PCR (qPCR) results showed that the mRNA expression levels of CXCL2, LYZ, and PARVB were significantly higher in the DLBCL group. CONCLUSIONS: We developed a genetic risk model based on NRGs to predict the prognosis of patients with DLBCL, which may assist in the selection of treatment drugs for these patients.

The relationship between dietary patterns derived from inflammation and cognitive impairment in patients undergoing hemodialysis.

Introduction: Dietary patterns were shown to be closely related to inflammation, which was independently associated with cognitive impairment (CI) in patients undergoing hemodialysis (HD). However, it remains unclear the influence of dietary patterns derived from inflammation on CI in this population. This study aimed to examine the association between dietary patterns derived from C-reactive protein (CRP) and interleukin-6 (IL-6) and CI in patients undergoing HD. Methods: Dietary intake was obtained from the simplified quantitative food frequency questionnaire. Reduced rank regression (RRR) was used to extract two dietary patterns, with IL-6 and CRP as response variables. Cognitive function was examined by the Montreal Cognitive Assessment (Beijing version). Venous blood was drawn for measuring IL-6 and CRP levels. Multivariable logistic regression was used to investigate the association between dietary patterns and CI. Results: Dietary pattern derived from IL-6 was not significantly associated with CI. The third quartile of dietary pattern, which used CRP as the response variable, significantly contributed to the increased risk of CI (AOR 8.62, 95% CI 1.47-50.67) after controlling age, sex, education level, marital status, and residential pattern (p-for-trend = 0.028). After considering hypertension and diabetes, physical activity level, anxiety and depression, smoking and drinking status, social support, energy intake, and the dietary pattern derived from IL-6 (p-for-trend = 0.026), the relationship between the dietary pattern derived from CRP and CI remained significant (AOR 14.54, 95% CI 1.40-151.13). Conclusion: Dietary pattern associated with high CRP level, including high intake of rice, liquor, fruit, tea and coffee and low intake of dark vegetables and juice, contributed to the increased risk of CI. The association between the consumption of seafood, sweet beverages, and alcohol and CI is yet to be established. However, they may be dietary contributing factors to inflammation in patients undergoing HD.

Massage therapy significantly improves cancer-related fatigue in cancer patients: a meta-analysis of randomized controlled trials.

PURPOSE: This study was designed to investigate the effectiveness and safety of massage therapy in cancer-related fatigue (CRF) and to provide a reference for the future management of CRF. METHODS: Eight databases (PubMed, Embase, Cochrane Library, CINAHL, Sinomed, Chinese Scientific Journal database (VIP), Wanfang, and China National Knowledge Infrastructure (CNKI)) were systematically reviewed from inception to May 2022 for randomized controlled trials. Two reviewers critically and independently assessed the risk of bias using Cochrane Collaboration criteria and extracted correlated data using the designed form. The meta-analysis was performed using RevMan 5.3 to calculate the pooled effect sizes and 95% confidence intervals (CIs). Sensitivity analysis was performed to find the source of the heterogeneity. Publication bias was assessed via funnel plot analysis and the Egger test. RESULT: A total of 11 qualified studies that included 789 patients (massage therapy group: 389; control group: 400) were included in the meta-analysis. Massage therapy had a marked effect on fatigue in cancer patients [standardized mean difference (SMD) = - 1.69, 95% CI (- 2.46, - 0.93), P < 0.01], especially in breast cancer [SMD = - 1.62, 95% CI (- 2.18, - 1.05), P < 0.01]. Reflexology [SMD = - 2.71, 95% CI (- 4.65, - 0.77), P < 0.01] and Chinese massage [SMD = - 1.14, 95% CI (- 1.95, - 0.33), P < 0.01] can have a more significant effect on fatigue. Massage time is 20 to 40 min [SMD = - 2.39, 95% CI (- 4.13, - 0.66), P < 0.01], twice a week [SMD = - 3.46, 95% CI (- 5.47, - 1.45), P < 0.01] for 3-5 weeks [SMD = - 2.36, 95% CI (- 3.53, - 1.19), P < 0.01], which is more effective in relieving fatigue in cancer patients. Five studies described the occurrence of adverse events and only two studies had adverse events. CONCLUSION: Massage therapy can be effective in relieving fatigue in cancer patients. Current evidence suggests that reflexology is the most effective approach to relieve fatigue, particularly in the breast cancer patients. The optimal intervention frequency and cycle for massage therapy is twice a week for 3-5 weeks, and the optimal duration is 20-40 min.

A competing risk-based nomogram to predict cancer-specific survival in patients with retroperitoneal leiomyosarcoma.

Considering the rarity and aggressive nature of retroperitoneal leiomyosarcoma (RLMS), several prognostic factors might contribute to the cancer-specific mortality of these patients. This study aimed to construct a competing risk-based nomogram to predict cancer-specific survival (CSS) for patients with RLMS. In total, 788 cases from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2015) were included. Based on the Fine & Gray's method, independent predictors were screened to develop a nomogram for predicting 1-, 3-, and 5-year CSS. After multivariate analysis, CSS was found significantly associated with tumor characteristics (tumor grade, size, range), as well as surgery status. The nomogram showed solid prediction power and was well calibrated. Through decision curve analysis (DCA), a favorable clinical utility of the nomogram was demonstrated. Additionally, a risk stratification system was developed and distinctive survival between risk groups was observed. In summary, this nomogram showed a better performance than the AJCC 8th staging system and can assist in the clinical management of RLMS.

AdipoRon Engages Microglia to Antinociception through the AdipoR1/AMPK Pathway in SNI Mice.

Background: Microglia-associated neuroinflammation plays a crucial role in the initiation and development of neuropathic pain (NeuP). AdipoRon is an analog of adiponectin that exerts an anti-inflammatory effect in various diseases through the adiponectin receptor 1 (AdipoR1) signaling mechanism. Adenosine monophosphate-activated protein kinase (AMPK) is a downstream target of AdipoR1, and the AdipoR1/AMPK pathway is involved in the regulation of inflammation. This study is aimed at investigating whether AdipoRon could alleviate NeuP by inhibiting the expression of microglia-derived tumor necrosis factor-alpha (TNF-α) through the AdipoR1/AMPK pathway. Methods: In vivo, the NeuP model was established in mice through the spared nerve injury. The von Frey test was used to detect the effect of AdipoRon on the mechanical paw withdrawal threshold. Western Blot was performed to detect the effects of AdipoRon on the expression of TNF-α, AdipoR1, AMPK, and p-AMPK. Immunofluorescence was performed to observe the effects of AdipoRon on spinal microglia. In vitro, lipopolysaccharide (LPS) was used to induce inflammatory responses in BV2 cells. The effect of AdipoRon on cell proliferation was detected by CCK-8. qPCR was used to examine the effects of AdipoRon on the expression of TNF-α and polarization markers. And the effect of AdipoRon on the AdipoR1/AMPK pathway was confirmed by Western Blot. Results: Intraperitoneal injection of AdipoRon alleviated mechanical nociception in SNI mice, and the application of AdipoRon reduced the expression of TNF-α and the number of microglia in the ipsilateral spinal cord. Additionally, AdipoRon decreased the protein level of AdipoR1 and increased the protein level of p-AMPK in the ipsilateral spinal cord. In vitro, AdipoRon inhibited BV2 cell proliferation and reversed LPS-induced TNF-α expression and polarization imbalance. Furthermore, AdipoRon reversed the LPS-induced increase in AdipoR1 expression and decrease in p-AMPK expression in BV2 cells. Conclusions: AdipoRon may alleviate NeuP by reducing microglia-derived TNF-α through the AdipoR1/AMPK pathway.

Modification and application of "zero-line" incision design in total endoscopic gasless unilateral axillary approach thyroidectomy: A preliminary report.

Introduction: Gasless unilateral trans-axillary approach (GUA) thyroidectomy has witnessed rapid development in technologies and applications. However, the existence of surgical retractors and limited space would increase the difficulty of guaranteeing the visual field and disturb safe surgical manipulation. We aimed to develop a novel zero-line method for incision design to access optimal surgical manipulation and outcomes. Methods: A total of 217 patients with thyroid cancer who underwent GUA were enrolled in the study. Patients were randomly classified into two groups (classical incision and zero-line incision), and their operative data were collected and reviewed. Results: 216 enrolled patients underwent and completed GUA; among them, 111 patients were classified into the classical group, and 105 patients were classified into the zero-line group, respectively. Demographic data, including age, gender, and the primary tumor side, were similar between the two groups. The duration of surgery in the classical group was longer (2.66 ± 0.68 h) than in the zero-line group (1.40 ± 0.47 h) (p < 0.001). The counts of central compartment lymph node dissection were higher in the zero-line group (5.03 ± 3.02 nodes) than that in the classical group (3.05 ± 2.68 nodes) (p < 0.001). The score of postoperative neck pain was lower in the zero-line group (1.0 ± 0.36) than that in the classical group (3.3 ± 0.54) (p < 0.05). The difference in cosmetic achievement was not statistically significant (p > 0.05). Conclusion: The "zero-line" method for GUA surgery incision design was simple but effective for GUA surgery manipulation and worth promoting.

Which Exercise Approaches Work for Relieving Cancer-Related Fatigue? A Network Meta-analysis.

OBJECTIVE: To determine the most effective exercise modalities for managing cancer-related fatigue during and after cancer treatment. DESIGN: Network meta-analysis (NMA) of randomized controlled trials. LITERATURE SEARCH: Seven electronic databases were systematically searched from inception to January 2022. STUDY SELECTION CRITERIA: Randomized controlled trials testing the effects of exercise on relieving cancer-related fatigue in adult patients with cancer. DATA SYNTHESIS: An NMA of 56 studies was conducted, and the PRISMA-NMA guidelines were followed when reporting results. To determine the most effective interventions, the surface under the cumulative ranking curve (SUCRA) value was calculated for each exercise modality. RESULTS: Combined aerobic and resistance exercise (standardized mean difference [SMD], 1.57; credible interval [CrI], 1.03-2.10), yoga (SMD, 1.02; CrI: 0.44, 1.60), and regular physical activity (SMD, 1.07; CrI: 0.21, 1.92) could significantly alleviate cancer-related fatigue compared to control groups (usual care, wait-list, and regular physical activity). Combined aerobic and resistance exercise (SUCRA, 97.2%) had the highest probability of efficacy, followed by yoga (SUCRA, 75.5%) and regular physical activity (SUCRA, 74.1%). During cancer treatment, combined aerobic and resistance exercise (SUCRA, 94.5%) ranked first in efficacy, followed by regular physical activity (SUCRA, 82.1%) and yoga (SUCRA, 73.8%). After cancer treatment, only combined aerobic and resistance exercise (SMD, 0.99; CrI: 0.13, 1.84) had a significant effect on cancer-related fatigue. CONCLUSION: Combined aerobic and resistance exercise, yoga, and regular physical activity were the most effective exercise modalities for alleviating cancer-related fatigue. Combined aerobic and resistance exercise is recommended during and after cancer treatment. J Orthop Sports Phys Ther 2023;53(6):1-10. Epub: 23 March 2023. doi:10.2519/jospt.2023.11251.

Comparison of femoral neck system vs. dynamic hip system blade for the treatment of femoral neck fracture in young patients: A retrospective study.

Background: Femoral neck fracture is a common fracture in orthopedic practice. This study aimed to compare the clinical outcomes between the femoral neck system and dynamic hip system blade for the treatment of femoral neck fracture in young patients. Methods: This retrospective study included 43 and 52 patients who underwent treatment for femoral neck fracture with the femoral neck system and dynamic hip system blade, respectively, between August 2019 and August 2020. Operative indexes, including operation duration, blood loss, incision length, postoperative complications (femoral neck shortening, non-union, screw pull-out, femoral head necrosis), and Harris scale scores were recorded and analyzed. Results: Compared to that with the dynamic hip system blade, the femoral neck system showed significantly less operation duration (femoral neck system vs. dynamic hip system blade: 47.09 ± 9.19 vs. 52.90 ± 9.64, P = 0.004), less blood loss (48.53 ± 10.69 vs. 65.31 ± 17.91, P < 0.001), and shorter incision length (4.04 ± 0.43 vs. 4.93 ± 0.53, P < 0.001). Femoral neck shortening was significantly lower with the femoral neck system than with the dynamic hip system blade (3.93 ± 2.40, n = 39 vs. 5.22 ± 2.89, n = 44, P = 0.031). No statistical differences were observed between the two groups in nonunion, screw pull-out, and femoral head necrosis. In addition, the latest follow-up Harris scale score was significantly higher with the femoral neck system than with the dynamic hip system blade (92.3 ± 4.5 vs. 89. 9 ± 4.9, P = 0.015). Conclusion: The femoral neck system results in less trauma, less femoral neck shortening, and better hip joint function than the dynamic hip system blade for the treatment of femoral neck fracture in young patients.

Inhibition of deubiquitinase USP28 attenuates cyst growth in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, which is characterized by progressive growth of multiple renal cysts in bilateral kidneys. In the past decades, mechanistic studies have entailed many essential signalling pathways that were regulated through post-translational modifications (PTMs) during cystogenesis. Among the numerous PTMs involved, the effect of ubiquitination and deubiquitination remains largely unknown. Herein, we identified that USP28, a deubiquitinase aberrantly upregulated in patients with ADPKD, selectively removed K48-linked polyubiquitination and reversed protein degradation of signal transducer and activator of transcription 3 (STAT3). We also observed that USP28 could directly interact with and stabilize c-Myc, a transcriptional target of STAT3. Both processes synergistically enhanced renal cystogenesis. Furthermore, pharmacological inhibition of USP28 attenuated the cyst formation both in vivo and in vitro. Collectively, USP28 regulates STAT3 turnover and its transcriptional target c-Myc in ADPKD. USP28 inhibition could be a novel therapeutic strategy against ADPKD.

Teratoma of the Tongue in a Fetus: A Case Report and Review of the Literature.

Teratomas are tumors composed of multiple embryonic germ layers of tissue, and those occurring in the tongue of the fetus are extremely rare. This paper reports the case of a 20-week-old fetus diagnosed with oral masses combined with a cleft lip and palate using prenatal ultrasonography. The patient decided to terminate the pregnancy due to economic factors after prenatal genetic consultation. The mother underwent induction termination and delivered a stillborn male fetus. The mass originated from the tongue and was pathologically confirmed as a mature teratoma by histology. Teratoma of the tongue is a rare congenital tumor that is usually benign. Its etiology is multifactorial, and prenatal karyotyping is necessary. Ultrasound is the main method of prenatal diagnosis, and magnetic resonance imaging is an effective complement to ultrasonography. Tumors can cause other malformations and abnormalities, and their location and size have an essential impact on prognosis. The imaging approach should focus on the associated abnormalities in order to assess the impact of the mass on the fetal airway and swallowing. Appropriate follow-up imaging can be helpful in the dynamic assessment of management.

miRNA-195-5p/PSAT1 feedback loop in human triple-negative breast cancer cells.

BACKGROUND: Substantial evidence suggests that non-coding RNAs, such as microRNAs (miRNAs), play a vital role in human cancer. Phosphoserine aminotransferase 1 (PSAT1) is a serine biosynthesis-related member of the aminotransferase family and is closely associated with worse prognosis in triple-negative breast cancer (TNBC). OBJECTIVE: The present study elucidated the molecular mechanisms underlying PSAT1 regulation by miRNAs in TNBC. METHODS: After collecting breast cancer and para-cancerous tissues, expression and functional testing of microRNA-195-5p (miR-195-5p) and PSAT1 were implemented both in vivo and in vitro. RESULTS: Abnormally low miR-195-5p expression was confirmed in TNBC tissues and cells. The specific targeting effect of miR-195-5p on PSAT1 was screened. Our observations revealed that biological tumor behavior was inhibited after miR-195-5p upregulation and this inhibition could be reversed by PSAT1 overexpression both in vivo and in vitro. CONCLUSION: Our study revealed the regulatory axis of miR-195-5p/PSAT1 in TNBC, suggesting a promising targeted therapy for clinical application.

Predictors of and predictive nomogram for cut-out of proximal femur nail anti-rotation device in intertrochanteric fractures.

PURPOSE: This study determined independent predictors and developed a predictive nomogram for failed correction of intertrochanteric fractures due to cut-out of the proximal femur nail anti-rotation (PFNA) device. METHODS: Demographic and radiological data of 592 adult patients with intertrochanteric fractures (AO 31A) treated by PFNA were collected retrospectively. Independent predictors of cut-out were obtained through univariate and multivariate analyses, and a predictive nomogram was established. The discrimination, calibration, and clinical utility of the nomogram were based on receiver operating characteristic curve (AUC), concordance index (C-index), calibration curve, and decision curve analysis, respectively. RESULTS: Overall, 18 (3.04%) cases of cut-out occurred. Independent predictors according to the multivariate analysis were body mass index (BMI), poor-to-acceptable quality of reduction, PFNA blade position, and tip-apex distance (TAD). AUC of the nomogram was 0.849, and C-index was 0.849 (95% CI [0.844-0.854]). Bootstrapping yielded a corrected C-index of 0.849. The calibration and decision curves indicated good agreement and clinical benefit of the nomogram. CONCLUSION: A reliable predictive nomogram was developed for cut-out of the PFNA in intertrochanteric fractures, based on BMI, quality of reduction, blade position, and TAD.

A SERPINE1-Based Immune Gene Signature Predicts Prognosis and Immunotherapy Response in Gastric Cancer.

Immune checkpoint inhibitors (ICIs) therapy has been successfully utilized in the treatment of multiple tumors, but only a fraction of patients with gastric cancer (GC) could greatly benefit from it. A recent study has shown that the tumor microenvironment (TME) can greatly affect the effect of immunotherapy in GC. In this study, we established a novel immune risk signature (IRS) for prognosis and predicting response to ICIs in GC based on the TCGA-STAD dataset. Characterization of the TME was explored and further validated to reveal the underlying survival mechanisms and the potential therapeutic targets of GC. The GC patients were stratified into high- and low-risk groups based on the IRS. Patients in the high-risk group, associated with poorer outcomes, were characterized by significantly higher immune function. Further analysis showed higher T cell immune dysfunction and probability of potential immune escape. In vivo, we detected the expressions of SERPINE1 by the quantitative real-time polymerase chain reaction (qPCR)in tumor tissues and adjacent normal tissues. In vitro, knockdown of SERPINE1 significantly attenuated malignant biological behaviors of tumor cells in GC. Our signature can effectively predict the prognosis and response to immunotherapy in patients with GC.

miR-182-5p attenuates Schistosoma japonicum-induced hepatic fibrosis by targeting tristetraprolin.

Egg granuloma formation in the liver is the main pathological lesion caused by Schistosoma japonicum infection, which generally results in liver fibrosis and may lead to death in advanced patients. MicroRNAs (miRNAs) regulate the process of liver fibrosis, but the putative function of miRNAs in liver fibrosis induced by S. japonicum infection is largely unclear. Here, we detect a new miRNA, miR-182-5p, which shows significantly decreased expression in mouse livers after stimulation by soluble egg antigen (SEA) of S. japonicum or S. japonicum infection. Knockdown or overexpression of miR-182-5p in vitro causes the increased or decreased expression of tristetraprolin (TTP), an important immunosuppressive protein in the process of liver fibrosis. Furthermore, knockdown of miR-182-5p in vivo upregulates TTP expression and significantly alleviates S. japonicum-induced hepatic fibrosis. Our data demonstrate that downregulation of miR-182-5p increases the expression of TTP in mouse livers following schistosome infection, which leads to destabilization of inflammatory factor mRNAs and attenuates liver fibrosis. Our results uncover fine-tuning of liver inflammatory reactions related to liver fibrosis caused by S. japonicum infection and provide new insights into the regulation of schistosomiasis-induced hepatic fibrosis.

Achaete-scute complex-like 2 regulated inflammatory mechanism through Toll-like receptor 4 activating in stomach adenocarcinoma.

BACKGROUND: To investigate the role of achaete-scute complex-like 2 (ASCL2) in stomach adenocarcinoma (STAD), we analyze whether ASCL2 suppression could retard cancer development and further observe the relevance between ASCL2 and inflammation via Toll-like receptor 4 (TLR4) activation in STAD, both in vitro and in vivo. METHODS: Proliferation, development, inflammation, and apoptosis in STAD are observed using sh-ASCL2 lentivirus via TLR4 activation in vitro and in vivo. The relationship between ASCL2 and inflammation is analyzed. Western blotting of ASCL2 with the target protein of immune-associated cells is performed. The prognosis of STAD and associated ASCL2 mutation are analyzed. RESULTS: The ASCL2 level in STAD tumor tissues is increased, compared to normal tissues, and brings a worse prognosis. The ASCL2 shows a negative correlation with inflammation, and TLR4 reveals a positive correlation with gastric cancer. ASCL2 expression is high in MGC803 cells. Sh-ASCL2 could reduce STAD development by decreasing proliferation, tumor volume, and biomarker levels and increasing apoptosis in vitro and in vivo. The inflammatory role of ASCL2 is regulated through TLR4 activation. ASCL2 levels may be related to CNTNAP3, CLIP1, C9orf84, ARIH2, and IL1R2 mutations; positively correlated with M2 macrophage and T follicular helper cell levels; negatively correlated with neutrophil, dendritic cell, monocyte, CD8 T cell, and M1 macrophage levels; and involved in STAD prognosis. CONCLUSIONS: The ASCL2 may adjust inflammation in STAD through TLR4 activation and may be associated with related immune cells. ASCL2 is possibly an upstream target factor of the TLR4 signaling pathway.