Transient hydroxycholesterol treatment restrains TCR signaling to promote long-term immunity.

T cell receptor (TCR) plays a fundamental role in adaptive immunity, and TCR-T cell therapy holds great promise for treating solid tumors and other diseases. However, there is a noticeable absence of chemical tools tuning TCR activity. In our study, we screened natural sterols for their regulatory effects on T cell function and identified 7-alpha-hydroxycholesterol (7a-HC) as a potent inhibitor of TCR signaling. Mechanistically, 7a-HC promoted membrane binding of CD3ε cytoplasmic domain, a crucial signaling component of the TCR-CD3 complex, through alterations in membrane physicochemical properties. Enhanced CD3ε membrane binding impeded the condensation between CD3ε and the key kinase Lck, thereby inhibiting Lck-mediated TCR phosphorylation. Transient treatments of TCR-T cells with 7a-HC resulted in reduced signaling strength, increased memory cell populations, and superior long-term antitumor functions. This study unveils a chemical regulation of TCR signaling, which can be exploited to enhance the long-term efficacy of TCR-T cell therapy.

Reducing greenhouse gas intensity using a mixture of controlled-release urea and common urea combining suitable maize varieties in a summer maize system.

The one-time application of common urea blended with controlled-release urea (CRU) is considered effective for improving nitrogen use efficiency and grain yield and reducing the greenhouse gas emissions of summer maize in intensive agricultural systems. However, the trade-off between the economic and environmental performances of different blended fertilizer treatments for different maize varieties remains unclear. Therefore, a consecutive two-year field experiment was conducted in the North China Plain to study the effects of different ratios of CRU and common urea on the yield, nitrous oxide (N2O) emissions, yield-scaled total N2O emissions, greenhouse gas intensity (GHGI), and net ecosystem economic benefit (NEEB) in 2021 and 2022. Four N fertilizer treatments with equal rate at 180 kg N ha-1 were applied as N180U (all Urea), N180C1(1/3CRU), N180C2(2/3CRU), and N180C (all CRU), and two maize varieties (JNK728-yellow ripe variety and ZD958-green ripe variety) were used. The N180C1 and N180C2 treatments produced the highest grain yield in varieties JNK728 and ZD958 (9.4-11.5 t ha-1 and 9.0-11.0 t ha-1), respectively. Compared to the N180U treatment (conventional method), the N180C1 treatment reduced the GHGI (24.8 %-25.9 %) and increased the NEEB (33.1 %-33.4 %) in the JNK728 variety, whereas the N180C2 treatment reduced the GHGI (16.9 %-28.8 %) and increased the NEEB (27.2 %-48.1 %) in the ZD958 variety. The study concludes that a one-time application of blended nitrogen fertilizer in suitable varieties can minimize the GHGI and maximize the NEEB, which is an effective strategy for balancing yield and nitrogen efficiency in the summer maize system in the North China Plain.

Does age affect patient outcomes after humeral head replacement in the treatment of acute proximal humeral fractures? A comparative cohort study with a minimum 10 years long-term follow-up.

BACKGROUND: Humeral head replacement (HHR) is now rarely recommended for complex proximal humeral fractures (PHFs) in older patients. However, in relatively young and active patients with unreconstructable complex PHFs, controversy still exists regarding the treatment options of reverse shoulder arthroplasty and HHR. The goal of this study was to compare the survival, functional, and radiographic outcomes of HHR in patients aged <70 years and those aged ≥70 years after a minimum 10 years follow-up. METHODS: Eighty-seven out of 135 patients undergoing primary HHR were enrolled and then divided into 2 groups based on age: <70 years and ≥70 years. Clinical and radiographic evaluations were performed with a minimum follow-up of 10 years. RESULTS: There were 64 patients (mean, 54.9 years) in the younger group and 23 patients (mean, 73.5 years) in the older group. The younger and older groups had comparable 10-year implant survivorship (98.4% vs. 91.3%). Patients aged ≥70 years had worse American Shoulder and Elbow Surgeons scores (74.2 vs. 81.0, P = .042) and lower satisfaction rates (12% vs. 64%, P < .001) than younger patients. At the final follow-up, older patients had worse forward flexion (117° vs. 129°, P = .047) and internal rotation (17 vs. 15, P = .036). More greater tuberosity complications (39% vs. 16%, P = .019), glenoid erosion (100% vs. 59%, P = .077), and humeral head superior migration (80% vs. 31%, P = .037) were also identified in patients aged ≥70 years. CONCLUSIONS: Unlike the increased risk for revision and functional deterioration over time after reverse shoulder arthroplasty for PHFs in younger patients, a high implant survival rate with lasting pain relief and stable functional outcomes could be observed in younger patients after HHR during long-term follow-up. Patients aged ≥70 years had worse clinical outcomes, lower patient satisfaction, more greater tuberosity complications, and more glenoid erosion and humeral head superior migration than those aged <70 years. HHR should not be recommended for the treatment of unreconstructable complex acute PHFs in older patient populations.

Impact of lateral cervical lymph node metastasis on lung metastasis in pediatric thyroid cancer: A correlation study.

BACKGROUND: Thyroid cancer (TC) frequently manifests with lung metastases in the pediatric population, occurring at a significant rate of 30 %. This study aims to evaluate the impact of regional patterns of cervical lymph node metastases on lung metastases in pediatric TC. METHODS: Retrospective analysis was conducted on data from pediatric TC patients spanning the years 2000 to 2018. We compared the rates of lymph node metastasis (LNR), the number of lymph node metastases, and the number of dissected lymph nodes in the central and lateral cervical regions between patients with and without lung metastases. Statistical methods were employed to adjust for confounders during hypothesis testing. RESULTS: A total of 227 pediatric patients, with a median age of 15.12 ± 2.84 years, were included in the study. Of these, 202 (89 %) exhibited LN metastasis, with 40(17.62 %) patients presenting with lung metastasis. Patients with lung metastases were found to be younger (13.40 ± 3.11 vs. 15.50 ± 2.64, p < 0.001), had larger primary tumor diameters (3.49 ± 1.98 vs. 2.31 ± 1.45, p < 0.001), and exhibited a higher number of lymph node metastases (23.40 ± 10.75 vs. 14.65 ± 13.16, p < 0.001). Notably, in patients with LN metastases, the presence of >12 lateral cervical lymph node metastases emerged as a significant risk factor for lung metastases. Among children with metachronous lung metastases, the median time to detection of lung metastases was 43 (12-132) months, and they appeared to receive a greater proportion of radioactive iodine (RAI) treatment compared to those with synchronous lung metastases. CONCLUSION: Lateral cervical lymph node metastasis independently predicts the likelihood of lung metastases in pediatric TC. Furthermore, our findings emphasize the importance of thorough examination of the lungs during follow-up, particularly when the number of metastatic lateral cervical lymph nodes exceeds 12.

Unified framework for terahertz radiation from a single- or two-color plasma filament.

The plasma filament induced by photo-ionization in transparent media (e.g., air) is a competitive terahertz (THz) source, whose mechanism has been widely studied in two separate schemes, i.e., the one- or two-color femtosecond laser filamentation. However, the physical commonality of these two schemes is less explored currently, and a common theory is in urgent need. Here, we proposed the traveling-wave antenna (TWA) model applicable to both single- and dual-color laser fields, which successfully reproduced the reported far-field THz angular distribution/dispersion from different filament lengths with either a constant or a varied plasma density. This work paves the way toward a deeper understanding of the important laser-filament-based THz sources within the same theoretical framework.

The Posterosuperior Tetralogy Scoring System as a Practical Tool to Predict Shoulder Function After Posterosuperior Large-to-Massive Rotator Cuff Repairs.

Background: Fatty infiltration (FI) or atrophy alone has been found to be inaccurate in predicting shoulder function after repair of large-to-massive rotator cuff tears (L/MRCTs), especially when a diverse extent of FI and atrophy presents in multiple rotator cuff muscles. Purpose/Hypothesis: The Posterosuperior Tetralogy Scoring System (PS-Tetra Score), which integrates FI and atrophy, was proposed to predict shoulder function after surgery. It was hypothesized was that a PS-Tetra Score ≥3 would be a risk factor for poor shoulder function after repair of posterosuperior L/MRCTs and would possess greater diagnostic value than using isolated FI or atrophy of the supraspinatus (SSP) or infraspinatus (ISP). Study Design: Case-control study; Level of evidence, 3. Methods: A total of 187 arthroscopic repairs of posterosuperior L/MRCTs were reviewed. Magnetic resonance imaging evaluations were performed of FI and atrophy of the SSP and ISP, teres minor hypertrophy, tendon retraction, and acromiohumeral distance. A postoperative American Shoulder and Elbow Surgeons (ASES) score of 70 was used to subgroup patients according to shoulder function. Univariate and multivariate analyses were performed to determine the risk factors of poor shoulder function (ASES ≤70). The diagnostic values of different indicators for predicting shoulder function were evaluated. Results: In univariate analysis, female sex, higher Goutallier grade of the SSP and ISP, positive SSP tangent sign, and PS-Tetra Score ≥3 was significantly associated with ASES score ≤70, whereas in binary logistic regression analysis, a PS-Tetra Score ≥3 was the only significant risk factor for poor shoulder function. The occurrence rate of poor function in shoulders with a PS-Tetra Score of 0, 1, 2, 3, and 4 was 0% (0/52), 0% (0/52), 19.57% (9/46), 58.06% (18/31), and 83.33% (5/6), respectively. PS-Tetra Score ≥3 possessed higher crude agreement (87.70%), specificity (90.97%), positive predictive value (62.16%), and area under the receiver operating characteristic curve (0.814) than the other 3 indicators, with relatively high negative predictive value (94.00%) and moderate sensitivity (71.88%). Conclusion: PS-Tetra Score ≥3 was a risk factor of poor shoulder function after repair of posterosuperior L/MRCTs and possessed greater diagnostic value than using isolated FI or atrophy of SSP or ISP alone for predicting shoulder function.

CT-based quantification of trachea shape to detect invasion by thyroid cancer.

OBJECTIVE: This study aims to develop a CT-based method for quantifying tracheal shape and evaluating its ability to distinguish between cases with or without tracheal invasion in patients with thyroid carcinoma. METHODS: A total of 116 quantitative shape features, including 56 geometric moments and 60 bounding shape features, were defined. The tracheal lumen was semi-automatically defined with a CT threshold of less than - 500 HU. Three contiguous slices with the 1st, 2nd, and 3rd smallest trachea lumen areas were contiguously selected, and the appropriate number of slices to be included was determined. Fifty-six patients with differentiated thyroid carcinoma (DTC) invading the trachea and 22 patients with DTC but without invasion were retrospectively included. A receiver operating characteristic (ROC) curve was applied to select the representative shape features and determine the optimal threshold. RESULTS: 23.3%, 25.9%, and 24.1% of the features displayed an area under the ROC curve (AUC) ≥ 0.800 when derived from 1, 2, and 3 slices, respectively. Calculating feature values from two slices with the 1st and 2nd smallest tracheal lumen area were considered appropriate. Six final features, including 3 geometric moments and 3 bounding shape features, were selected to determine the tracheal invasion status of DTC and displayed AUCs of 0.875-0.918, accuracies of 0.821-0.891, sensitivities of 0.813-0.893, and specificities of 0.818-0.932, outperforming the visual evaluation results. CONCLUSIONS: Geometric moments and bounding shape features can quantify the tracheal shape and are reliable for identifying DTC tracheal invasion. The selected features quantified the extent of tracheal deformity in DTC patients with and without tracheal invasion. CLINICAL RELEVANCE STATEMENT: Six geometric features provide a non-invasive, semi-automated evaluation of the tracheal invasion status of thyroid cancer. KEY POINTS: • A novel method for quantifying tracheal shape using 56 geometric moments and 60 bounding shape features was developed. • Six features identify tracheal invasion by thyroid carcinoma. • The selected features quantified the extent of tracheal deformity in differentiated thyroid carcinoma patients with and without tracheal invasion.

What Are the Long-term Outcomes of Locking Plates for Nonosteoporotic Three-part and Four-part Proximal Humeral Fractures With a Minimum 10-year Follow-up Period?

BACKGROUND: Proximal humeral fractures (PHFs) often occur in elderly individuals who experience low-energy falls. Open reduction and internal fixation (ORIF) of the proximal humerus is typically performed in young, active patients because of their good bone quality and high functional demands. Although good short-term results have been reported after ORIF in young patients, few studies have specifically evaluated long-term outcomes. QUESTIONS/PURPOSES: (1) What are the long-term clinical outcomes scores and (2) radiologic outcomes of nonosteoporotic three-part and four-part PHFs treated with locking plates? (3) What complications occurred after treatment, and what factors are associated with poor postoperative functional outcomes scores and avascular necrosis (AVN) of the humeral head after ORIF? METHODS: Between June 2005 and December 2012, we surgically treated 774 patients for displaced two-, three-, and four-part PHFs. Approximately 75% (581 of 774) underwent ORIF, 10% (77 of 774) underwent hemiarthroplasty, 7% (54 of 774) underwent intramedullary nailing, 5% (39 of 774) underwent reverse shoulder arthroplasty, and the remaining 3% (23 of 774) underwent other surgical treatments. We considered those who had ORIF as potentially eligible. Based on that criterion, 75% (581) were eligible. However, only patients with nonosteoporotic three- and four-part PHFs (cortical thickness of the proximal humeral diaphysis greater than 6 mm on a preoperative AP radiograph of the affected shoulder) and a minimum of 10 years of follow-up were included. Sixty-four percent (498 of 774) of the patients were excluded because of simple or osteoporotic fractures, 1% (7 of 774) were excluded because of ipsilateral limb multiple fractures, 0.3% (2 of 774) were excluded because of pathologic PHFs, and another 2% (13 of 774) were lost before the minimum study follow-up of 10 years, leaving 8% (61 of 774) for analysis here. The mean age at surgery was 45 ± 12 years, with a mean follow-up of 13 years. Fifty-seven percent (35 of 61) of the patients were men. Patient-reported outcomes were evaluated using the University of California Loas Angeles (UCLA) score (range 0 to 35; higher scores represent better shoulder function) and Constant score (range 0 to 100; higher scores represent better shoulder function) at least 10 years postoperatively. Postoperative radiographs were reviewed to assess the cortical bone thickness of the proximal humerus, neck-shaft angle, head-to-tuberosity distance, and radiologically confirmable complications. Logistic regression analysis was performed to evaluate factors associated with poor postoperative functional scores (UCLA score ≤ 27 or Constant score ≤ 70) and AVN of the humeral head; the association between AVN and postoperative functional outcomes was also assessed. RESULTS: At the most-recent follow-up, these patients had a mean UCLA score of 31 ± 3 and a Constant score of 88 ± 10. The mean neck-shaft angle was 133° ± 10°, and 23% (14 of 61) of patients experienced AVN of the humeral head during follow-up. Twenty-nine complications in 30% (18 of 61) of patients were reported. After controlling for potentially confounding variables such as age and gender, we found that the presence of greater tuberosity malposition (odds ratio 18 [95% confidence interval 2 to 167]; p = 0.01) and immediate postoperative neck-shaft angle less than 130° (OR 19 [95% CI 3 to 127]; p = 0.002) were associated with poor postoperative functional scores. Four-part PHFs (OR 13 [95% CI 2 to 82]; p = 0.008) and metaphyseal extension less than 8 mm (OR 7 [95% CI 1 to 35]; p = 0.03) were associated with AVN of the humeral head. For patients who met the criteria for anatomic reduction (achievement of all of the following three criteria: neck-shaft angle ≥ 130°, head-shaft displacement < 5 mm, and head-to-tuberosity distance greater than or equal to 3 mm and less than or equal to 20 mm), there were no differences in postoperative functional scores between patients with AVN and those without. CONCLUSION: ORIF of nonosteoporotic proximal humeral fractures with locking plates led to favorable functional and radiologic outcomes at a minimum of 10 years of follow-up. When encountering complex PHFs in patients with good bone quality, every effort must be made to achieve an anatomic reduction of the fracture as far as possible, which may not reduce the risk of AVN (this occurred in nearly one-fourth of patients). However, good outcomes can usually be expected, even in patients with AVN. Because this was a retrospective study with a high risk of bias owing to sparse data, the factors associated with poor postoperative functional outcomes must be further investigated in large prospective studies. LEVEL OF EVIDENCE: Level III, therapeutic study.

Kruppel-like factor 13 acts as a tumor suppressor in thyroid carcinoma by downregulating IFIT1.

BACKGROUND: Kruppel-like factor 13 (KLF13) is a transcription factor and plays an important role in carcinogenesis. However, the significance of KLF13 in thyroid carcinoma (THCA) is underdetermined. In this study, we aimed to explore the clinical relevance and function of KLF13 in the progress of THCA. METHODS: The expression of KLF13 in thyroid carcinoma and normal tissue was investigated by qPCR and IHC assay. The expression of KLF13 and IFIT1 in cell samples was investigated with Western blot assay. Cell proliferation ability was detected with CCK8 and colony formation assay. Cell growth in vivo with or without KLF13 overexpression was evaluated on a xenograft model. Cell migration ability was measured with Transwell assay. Cell cycle was detected with flow cytometer. The downstream genes of KLF13 were screened using RNA-seq assay. Luciferase activity was employed to assess the transcriptional regulation of KLF13 on IFIT1 promoter. RESULTS: KLF13 expression was downregulated in THCA samples. KLF13 knockdown and overexpression promoted and inhibited the proliferation and migration of THCA cells, respectively. The RNA-seq, RT-qPCR and immunoblotting data showed that KLF13 knockdown significantly potentiated IFIT1 expression at both mRNA and protein levels. Luciferase assays showed that KLF13 suppressed the transcription activity of IFIT1 promoter. Besides, IFIT1 upregulation was critical for the proliferation and migration of THCA cell lines. Lastly, silencing of IFIT1 greatly reversed the proliferation and migration induced by KLF13 knockdown. CONCLUSIONS: In conclusion, KLF13 may function as an anti-tumor protein in THCA by regulating the expression of IFIT1 and offer a theoretical foundation for treating thyroid carcinoma.

The role of multifocality in predicting central lymph node metastasis in initially treated 18-55 years old female patients with unilateral papillary thyroid microcarcinoma.

Objective: To determine the predictive ability of multifocality for central lymph node metastasis in initially treated 18-55 years old female patients with unilateral papillary thyroid microcarcinoma. Study design: Retrospective review. Setting: Tertiary medical center. Methods: We retrospectively collected clinical data from initially treated papillary thyroid microcarcinoma (PTMC) patients at Cancer Hospital Chinese Academy of Medical and sciences between January 1st, 2018, and December 31st, 2018. Data from 975 initially treated 18-55 years old female patients with unilateral PTMC was collected. We also collected data from 340 initially treated 18-55 years old male patients with unilateral PTMC patients to compare the results between genders. Clinicopathological factors associated with central lymph node metastasis (CLNM) were investigated by univariate and multivariate analysis. Results: (1) In the female group, there were 196 (20.1%) cases that had tumor multifocality, including 126 (12.9%) with 2 foci and 70 (7.2%) with >2 foci. The risk of CLNM in patients with 2 foci was not significantly higher than patients with 1 focus (37.3% vs 38.6%, P=0.775). However, diagnosed with >2 foci were independently and positively correlated with CLNM (OR=2.708, 95%CI=1.592-4.607, P<0.001), as was tumor diameter >0.55cm (OR=2.047, 95%CI=1.535-2.730, P<0.001). (2) In the male group, the risk of CLNM with 2 foci was significantly higher than 1 focus (P=0.008). Compared to female patients, the risk of CLNM was significantly higher in patients with 1 focus (P<0.001) or 2 foci (P<0.001). Conclusion: In summary, the risk of CLNM in patients with 2 foci was not significantly higher than patients with 1 focus, while multifocality with over 2 foci was an independent risk factor of CLNM. Therefore, multifocality in this subgroup should not be simply defined as "more than 1 focus". Future models that include multifocality as a predictive factor for cervical lymph node metastasis could consider stratifying the cohort into smaller subgroups for more accurate conclusions.

Design and Implementation of a Multidisciplinary High-Fidelity Simulation Course for the Management of Malignant Spinal Cord Compression.

High-fidelity simulation (HFS) training is suited to high-stakes, uncommon situations such as malignant spinal cord compression (MSCC), allowing for rare hands-on practice. This pilot study was created as the first of its kind to examine educational outcomes of a radiation therapist (RTT)-led multidisciplinary radiation oncology (RO) emergency simulation course. A multidisciplinary course design team composed of RO residents, radiation oncologists, RTT course instructors, and medical physicists created a high-fidelity MSCC simulation course using collaboratively developed learning goals. Fifteen learners including RO residents, senior RTT students, and a medical physics (MP) resident participated in a live, RTT-facilitated simulation. Participants completed anonymized pre- and post-simulation standard interdisciplinary education perception (IEP) scales and a course evaluation assessing educational outcomes. Standard IEP questionnaire results showed highly favorable perceptions of respondents' own specialty and other allied specialties, with mean total pre-simulation scores of 91.76 and post-simulation scores of 94.23. The course evaluation assessed 10 learning objective domains, with significant improvements seen in self-rated post-course knowledge in 9 domains. Pre-course evaluations showed that 6/15 participants agreed or strongly agreed that they felt comfortable in their knowledge of all included domains; after course completion, 14/15 participants agreed or strongly agreed they felt comfortable in all domains. Collaboratively designed and led HFS courses are not only viable but can be an effective means of improving learning outcomes for RO residents, RTT students, and MP residents.

Case report: Complete response of an anaplastic thyroid carcinoma patient with NRAS Q61R/BRAF D594N mutations to the triplet of dabrafenib, trametinib and PD-1 antibody.

Anaplastic thyroid carcinoma, BRAF non-V600, NRAS, combination immunotherapy and targeted therapy, case report. Anaplastic thyroid carcinoma (ATC) is a rare type of thyroid cancer with a mortality rate near 100%. BRAF V600 and NRAS mutations are the most common drivers of ATC. While patients with BRAF V600-mutated ATC can be treated with BRAF-targeted therapy, there is no effective treatment for ATC driven by NRAS or non-V600 BRAF mutations. For patients with untargetable driver mutations, immunotherapy provides an alternative treatment option. Here, we present a metastatic ATC patient with PD-L1 positive (tumor proportion score of 60%) tumor and NRAS Q61R/BRAF D594N mutations, who progressed on PD-1 antibody sintilimab plus angiogenesis inhibitor anlotinib. The class 3 BRAF mutant D594N is sensitive to the inhibition of MEK inhibitor trametinib, and its oncogenic activity also depends on CRAF, which can be inhibited by BRAF inhibitor dabrafenib. For these reasons, the patient received a salvage treatment regime of dabrafenib, trametinib, and sintilimab, which resulted in a complete pathological response. To our best knowledge, this is the first report of successful treatment of ATC patients with concurrent NRAS/BRAF non-V600 mutations with the combination of immunotherapy and targeted therapy. Further investigation is required to decipher the mechanism by which the combination of dabrafenib/trametinib with PD-1 antibody overcomes initial immunotherapy resistance likely mediated by concurrent BRAF and NRAS mutations.

[Long-term effectiveness of arthroscopic partial repair for massive irreparable rotator cuff tears].

Objective: To explore the long-term effectiveness of arthroscopic partial repair in treatment of massive irreparable rotator cuff tears from both the radiological and clinical perspectives. Methods: A retrospective analysis was conducted on the clinical data of 24 patients (25 sides) with massive irreparable rotator cuff tears who met the inclusion criteria between May 2006 and September 2014. Among them, there were 17 males (18 sides) and 7 females (7 sides) with an age range of 43-67 years (mean, 55.0 years). There were 23 cases of unilateral injury and 1 case of bilateral injuries. All patients were treated with the arthroscopic partial repair. The active range of motion of forward elevation and abduction, external rotation, and internal rotation, as well as the muscle strength for forward flexion and external rotation, were recorded before operation, at the first postoperative follow-up, and at last follow-up. The American Association of Shoulder and Elbow Surgeons (ASES) score, the University of California at Los Angeles (UCLA) shoulder scoring, and Constant score were used to evaluate shoulder joint function. And the visual analogue scale (VAS) score was used to evaluate shoulder joint pain. MRI examination was performed. The signal-to-noise quotient (SNQ) was measured above the anchor point near the footprint area (m area) and above the glenoid (g area) in the oblique coronal T2 fat suppression sequence. The atrophy of the supraspinatus muscle was evaluated using the tangent sign. The global fatty degeneration index (GFDI) was measured to assess fat infiltration in the supraspinatus muscle, infraspinatus muscle, teres minor muscle, upper and lower parts of the subscapularis muscle. The mean GFDI (GFDI-5) of 5 muscles was calculated. Results: The incisions healed by first intention. All patients were followed up with the first follow-up time of 1.0-1.7 years (mean, 1.3 years) and the last follow-up time of 7-11 years (mean, 8.4 years). At last follow-up, the range of motion and muscle strength of forward elevation and abduction, ASES score, Constant score, UCLA score, and VAS score of the patients significantly improved when compared with those before operation ( P<0.05). Compared with the first follow-up, except for a significant increase in ASES score ( P<0.05), there was no significant difference in the other indicators ( P>0.05). Compared with those before operation, the degree of supraspinatus muscle infiltration worsened at last follow-up ( P<0.05), GFDI-5 increased significantly ( P<0.05), and there was significant difference in the tangent sign ( P<0.05); while there was no significant difference in the infiltration degree of infraspinatus muscle, teres minor muscle, and subscapularis muscle, upper and lower parts of the subscapularis muscle ( P>0.05). Compared with the first follow-up, the SNQm and SNQg decreased significantly at last follow-up ( P<0.05). At the first and last follow-up, there was no correlation between the SNQm and SNQg and the ASES score, Constant score, UCLA score, and VAS score of the shoulder ( P>0.05). Conclusion: Arthroscopic partial repair is effective in treating massive irreparable rotator cuff tear and significantly improves long-term shoulder joint function. For patients with severe preoperative fat infiltration involving a large number of tendons and poor quality of repairable tendons, it is suggested to consider other treatment methods.

[Clinical and radiologic outcomes after tendon insertion medialized repair of large-to-massive rotator cuff tears].

Objective: To evaluate the effectiveness of tendon insertion medialized repair in treatment of large-to-massive rotator cuff tears (L/MRCT). Methods: The clinical and imaging data of 46 L/MRCT patients who underwent arthroscopic insertion medialized repair between October 2015 and June 2019 were retrospectively analyzed. There were 26 males and 20 females with an average age of 57.7 years (range, 40-75 years). There were 20 cases of large rotator cuff tears and 26 cases of massive rotator cuff tears. Preoperative imaging evaluation included fatty infiltration (Goutallier grade), tendon retraction (modified Patte grade), supraspinatus tangent sign, acromiohumeral distance (AHD), and postoperative medializaiton length and tendon integrity. The clinical outcome was evaluated by visual analogue scale (VAS) score, American Society for Shoulder and Elbow Surgery (ASES) score, shoulder range of motion (including anteflexion and elevation, lateral external, and internal rotation) and anteflexion and elevation muscle strength before and after operation. The patients were divided into two groups (the intact tendon group and the re-teared group) according to the integrity of the tendon after operation. According to the medializaiton length, the patients were divided into group A (medialization length ≤10 mm) and group B (medialization length >10 mm). The clinical function and imaging indexes of the patients were compared. Results: All patients were followed up 24-56 months, with an average of 31.8 months. At 1 year after operation, MRI showed that the medializaiton length of supraspinatus tendon was 5-15 mm, with an average of 10.26 mm, 33 cases in group A and 13 cases in group B. Eleven cases (23.91%) had re-teared, including 5 cases (45.45%) of Sugaya type Ⅳ and 6 cases (54.55%) of Sugaya type Ⅴ. At last follow-up, the VAS score, ASES score, shoulder anteflexion and elevation range of motion, lateral external rotation range of motion, and anteflexion and elevation muscle strength significantly improved when compared with those before operation ( P<0.05); there was no significant difference in internal rotation range of motion between pre- and post-operation ( P>0.05). The Goutallier grade and modified Patte grade of supraspinatus muscle in the re-teared group were significantly higher than those in the intact tendon group, and the AHD was significantly lower than that in the intact tendon group ( P<0.05). There was no significant difference in other baseline data between the two groups ( P>0.05). Except that the ASES score of the intact tendon group was significantly higher than that of the re-teared group ( P<0.05), there was no significant difference in the other postoperative clinical functional indicators between the two groups ( P>0.05). There was no significant difference in the incidence of re-tear, VAS score, ASES score, range of motion of shoulder joint, and anteflexion and elevation muscle strength between group A and group B ( P>0.05). Conclusion: Tendon insertion medialized repair may be useful in cases with L/MRCT, and shows good postoperative shoulder function. Neither tendon integrity nor medialization length shows apparent correlations with postoperative shoulder function.

Intermittent F-actin Perturbations by Magnetic Fields Inhibit Breast Cancer Metastasis.

F-actin (filamentous actin) has been shown to be sensitive to mechanical stimuli and play critical roles in cell attachment, migration, and cancer metastasis, but there are very limited ways to perturb F-actin dynamics with low cell toxicity. Magnetic field is a noninvasive and reversible physical tool that can easily penetrate cells and human bodies. Here, we show that 0.1/0.4-T 4.2-Hz moderate-intensity low-frequency rotating magnetic field-induced electric field could directly decrease F-actin formation in vitro and in vivo, which results in decreased breast cancer cell migration, invasion, and attachment. Moreover, low-frequency rotating magnetic fields generated significantly different effects on F-actin in breast cancer vs. noncancerous cells, including F-actin number and their recovery after magnetic field retrieval. Using an intermittent treatment modality, low-frequency rotating magnetic fields could significantly reduce mouse breast cancer metastasis, prolong mouse survival by 31.5 to 46.0% (P < 0.0001), and improve their overall physical condition. Therefore, our work demonstrates that low-frequency rotating magnetic fields not only can be used as a research tool to perturb F-actin but also can inhibit breast cancer metastasis through F-actin modulation while having minimum effects on normal cells, which reveals their potential to be developed as temporal-controlled, noninvasive, and high-penetration physical treatments for metastatic cancer.

Do Radiation Oncology Residents Have a Preferred Radiation Treatment Planning Review Format?

In an era of increasing virtual communication, we aimed to investigate current formats used by radiation oncology residents for reviewing radiation treatment plans with attendings, preferences for formats, and reasons contributing to preferences. Residents enrolled in Canadian radiation oncology programs received questionnaires examining training level, typical review formats, preferred format, and reasons for preference. Analysis excluded PGY-1s due to insufficient exposure. Fifty-two residents participated. National response rate was 55%. Overall, hybrid review was the most used format (77%). Virtual review was the most preferred format (44%). Preference for virtual review was most common among junior residents (57%), while in-person review was most preferred by senior residents (45.4%). Few residents typically use their preferred format (35%). Reasons for preference varied between groups in convenience (p < 0.01), interactivity (p < 0.01), and teaching quality (p = 0.04). The persistence of e-learning suggests that virtual treatment planning education will continue to some degree. Junior residents prefer virtual review, while a clearly preferred review format was less apparent among senior residents. Preferences are multifactorial, and the trends seen in reasons for preference between formats may reflect advantages inherent to each. Progress is still needed in optimizing treatment planning education, as suggested by few residents using their preferred format. Residents and staff should collectively decide which educational format for treatment planning best meets educational needs.

Fourteen years old as the best age cutoff to differentiate prepubertal from pubertal papillary thyroid carcinoma.

BACKGROUND: It is unclear whether differences in clinical presentation and/or prognosis exist between prepubertal papillary thyroid cancer (PTC) and pubertal PTC. At present, there is a lack of definition for the appropriate cutoff age to define prepubertal PTC. METHODS: This study retrospectively reviewed 227 pediatric PTC patients (aged ≤18 years) who underwent initial surgery from March 2000 to December 2018. The median duration of follow-up was 85 months (range, 8-258). RESULTS: The age range was basically linearly related to multiple risk factors, such as T3-T4 disease, distant metastasis. Age (p = 0.032) was an independent risk factor for recurrence and persistent disease. Patients aged <14 years had obviously higher rates of extensive disease. The 10-year disease-free survival (DFS) rate of patients aged <14 years was 59.5% and that of patients aged ≥14 years was 82.6% (p = 0.004). CONCLUSIONS: Fourteen years of age may be an appropriate cutoff to differentiate prepubertal PTC from pubertal PTC.

A modified tracheal transection approach for cervical esophageal lesion treatment: A report of 13 cases.

Background: Surgical interventions for tumors in the cervical esophageal region are complicated and laryngeal function is frequently sacrificed. Therefore, we attempted the tracheal transection approach to resect the tumor while preserving laryngeal function. Methods: Three patients with papillary thyroid cancer (PTC), six with cervical esophageal cancer (CEC), and four with CEC mixed with thoracic esophageal cancer (TEC) were enrolled. The esophagus was exposed after the trachea was transected between the second and third tracheal rings. CEC/TEC: Resection of the esophagus or/and a portion of the hypopharynx with acceptable safety margins and repair with free jejunum or tubular stomach. PTC: Suture the small esophageal incision immediately after removing the tumor. The tracheal dissection was repaired with interrupted sutures throughout the entire layer after the esophageal lesion was resected. The status of the recurrent laryngeal nerve (RLN) determined whether a tracheotomy was necessary. Results: All 13 patients had effective esophageal lesion excision, with six of them requiring intraoperative tracheotomy. Postoperative complications included a tracheoesophageal fistula (one case, 7.7%), postoperative RLN paralysis (two cases, 15.4%), and aspiration (three cases, 23.1%). Except for two patients with distant metastases, there was no recurrence in the remaining patients after 5-92 months of follow-up. Conclusion: The tracheal transection approach, as a new surgical technique, can retain laryngeal function while ensuring appropriate exposure and satisfactory surgical resection. Before surgery, the feasibility of this approach must be carefully assessed. The RLN should be protected during the procedure. The operation is both safe and effective, with a wide range of applications.

Cardioprotective Mechanism and Active Compounds of Folium Ginkgo on Adriamycin-Induced Cardiotoxicity: A Network Pharmacology Study.

Objective: To investigate the mechanism of Folium Ginkgo (FG) against adriamycin-induced cardiotoxicity (AIC) through a network pharmacology approach. Methods: Active ingredients of FG were screened by TCMSP, and the targets of active ingredient were collected by Genclip3 and HERB databases. AIC-related target genes were predicted by Genecards, OMIM, and CTD databases. Protein-protein interaction (PPI) network was constructed by STRING platform and imported into Cytoscape software to construct the FG-active ingredients-targets-AIC network, and CytoNCA plug-in was used to analyze and identify the core target genes. The Metascape platform was used for transcription factor, GO and signaling pathway enrichment analysis. Results: 27 active ingredients of FG and 1846 potential targets were obtained and 358 AIC target genes were retrieved. The intersection of FG and AIC targets resulted in 218 target genes involved in FG action. The top 5 active ingredients with most targets were quercetin, luteolin, kaempferol, isorhamnetin, and sesamin. After constructing the FG-active ingredients-targets-AIC network, CytoNCA analysis yielded 51 core targets, of which the top ranked target was STAT3. Ninety important transcription factors were enriched by transcription factor enrichment analysis, including RELA, TP53, NFKB1, SP1, JUN, STAT3, etc. The results of GO enrichment analysis showed that the effective active ingredient targets of FG were involved in apoptotic signaling, response to growth factor, cellular response to chemical stress, reactive oxygen species metabolic process, etc. The signaling pathway enrichment analysis showed that there were many signaling pathways involved in AIC, mainly including pathways in cancer, FOXO signaling pathway, AGE-RAGE signaling pathway in diabetic complications, signaling by interleukins, and PI3K-AKT signaling pathway,. Conclusions: The study based on a network pharmacology approach demonstrates that the possible mechanisms of FG against AIC are the involvement of multicomponents, multitargets, and multipathways, and STAT3 may be a key target. Further experiments are needed to verify the results.