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Two cases of complicated pain exist: posterior screw fixation and myofascial pain. Intramuscular pulsed radiofrequency (PRF) may be an alternative treatment for such patients. This is a two-stage animal study. In the first stage, two muscle groups and two nerve groups were subdivided into a high-temperature group with PRF at 58 °C and a regular temperature with PRF at 42 °C in rats. In the second stage, two nerve injury groups were subdivided into nerve injury with PRF 42 °C on the sciatic nerve and muscle. Blood and spinal cord samples were collected. In the first stage, the immunohistochemical analysis showed that PRF upregulated brain-derived neurotrophic factor (BDNF) in the spinal cord in both groups of rats. In the second stage, the immunohistochemical analysis showed significant BDNF and tropomyosin receptor kinase B (TrkB) expression within the spinal cord after PRF in muscles and nerves after nerve injury. The blood biomarkers showed a significant increase in BDNF levels. PRF in the muscle in rats could upregulate BDNF-TrkB in the spinal cord, similar to PRF on the sciatica nerve for pain relief in rats. PRF could be considered clinically for patients with complicated pain and this study also demonstrated the role of BDNF in pain modulation. The optimal temperature for PRF was 42 °C.

Introduction: Most adrenal tumors are benign and primary adrenal malignancies are relatively rare. Primary adrenal lymphoma (PAL) is a very rare and highly aggressive malignant tumor with unknown etiology, atypical clinical symptoms, nonspecific imaging manifestations, difficult disease diagnosis and poor prognosis., Case Report: This case report details a 42-year-old woman who was admitted to the hospital with a 1-year-old bilateral adrenal mass and 1-month-old left upper abdominal pain. Enhanced CT of the abdomen showed a right adrenal nodule and a large occupying lesion in the left adrenal region, with a high probability of pheochromocytoma. Intraoperatively, a huge tumor measuring about 12*12*10 cm was found in the left adrenal region, infiltrating the left kidney, spleen and pancreatic tail. Postoperative pathology: lymphocytes were found in the renal capsule and subcapsule, lymphocytes were found in the pancreas; lymphocytes were found in the spleen. Consider a tumor of the lymphohematopoietic system, possibly lymphoma., Conclusion: This case demonstrates that primary adrenal diffuse large B-cell lymphoma (PADLBCL) is highly aggressive, has a poor prognosis, is prone to recurrence, has poor therapeutic outcomes, and is difficult to diagnose. Clinicians should consider the possibility of PADLBCL when encountering huge adrenal-occupying lesions and consider chemotherapy before surgery. Reducing the tumor size before surgery is a more favorable therapeutic approach, thus prolonging the patient life and improving the quality of survival., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare plasma cell (PC) neoplasm with associated paraneoplastic syndrome. According to the current diagnostic criteria, peripheral polyneuropathy and monoclonal PC proliferative disorder represent two mandatory criteria., Case Presentation: We report a 54-year-old male with peripheral neuropathy of bilateral lower limbs, sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF) levels, splenomegaly, extravascular volume overload, endocrinopathy, and skin hemangiomas. Of note, serum and urine protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) of this patient indicated undetectable M-protein and the normal ratio of free light chains κ and λ (FLC-R (κ/λ)). No monoclonal PCs were found in bone marrow examinations or biopsy of diseased bones. However, his clinical manifestations matched most of the diagnostic criteria. After excluding other diseases that are easily confused with POEMS syndrome, the diagnosis of variant POEMS syndrome with undetectable M-protein was proposed. The patient obtained clinically significant improvement and elevated VEGF returned to normal after 6 months of treatment with lenalidomide plus dexamethasone., Conclusions: Monoclonal PC dyscrasia (M-protein) while being a mandatory criterion for POEMS syndrome is undetectable in a considerable amount of patients that otherwise demonstrate typical symptoms. Here, we reported a case of variant POEMS syndrome with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting PCs but no evidence of M-protein. Therefore, negative results in M-protein and monoclonal PCs aren't enough to reject the diagnosis of POEMS syndrome. It is imperative to recognize the variant form of POEMS syndrome., (© 2024. The Author(s).)

Background: Tranexamic acid, an antifibrinolytic agent, might attenuate haematoma growth after an intracerebral haemorrhage. We aimed to determine whether treatment with intravenous tranexamic acid within 2 h of an intracerebral haemorrhage would reduce haematoma growth compared with placebo., Methods: STOP-MSU was an investigator-led, double-blind, randomised, phase 2 trial conducted at 24 hospitals and one mobile stroke unit in Australia, Finland, New Zealand, Taiwan, and Viet Nam. Eligible participants had acute spontaneous intracerebral haemorrhage confirmed on non-contrast CT, were aged 18 years or older, and could be treated with the investigational product within 2 h of stroke onset. Using randomly permuted blocks (block size of 4) and a concealed pre-randomised assignment procedure, participants were randomly assigned (1:1) to receive intravenous tranexamic acid (1 g over 10 min followed by 1 g over 8 h) or placebo (saline; matched dosing regimen) commencing within 2 h of symptom onset. Participants, investigators, and treating teams were masked to group assignment. The primary outcome was haematoma growth, defined as either at least 33% relative growth or at least 6 mL absolute growth on CT at 24 h (target range 18-30 h) from the baseline CT. The analysis was conducted within the estimand framework with primary analyses adhering to the intention-to-treat principle. The primary endpoint and secondary safety endpoints (mortality at days 7 and 90 and major thromboembolic events at day 90) were assessed in all participants randomly assigned to treatment groups who did not withdraw consent to use any data. This study was registered with ClinicalTrials.gov, NCT03385928, and the trial is now complete., Findings: Between March 19, 2018, and Feb 27, 2023, 202 participants were recruited, of whom one withdrew consent for any data use. The remaining 201 participants were randomly assigned to either placebo (n=98) or tranexamic acid (n=103; intention-to-treat population). Median age was 66 years (IQR 55-77), and 82 (41%) were female and 119 (59%) were male; no data on race or ethnicity were collected. CT scans at baseline or follow-up were missing or of inadequate quality in three participants (one in the placebo group and two in the tranexamic acid group), and were considered missing at random. Haematoma growth occurred in 37 (38%) of 97 assessable participants in the placebo group and 43 (43%) of 101 assessable participants in the tranexamic acid group (adjusted odds ratio [aOR] 1·31 [95% CI 0·72 to 2·40], p=0·37). Major thromboembolic events occurred in one (1%) of 98 participants in the placebo group and three (3%) of 103 in the tranexamic acid group (risk difference 0·02 [95% CI -0·02 to 0·06]). By 7 days, eight (8%) participants in the placebo group and eight (8%) in the tranexamic acid group had died (aOR 1·08 [95% CI 0·35 to 3·35]) and by 90 days, 15 (15%) participants in the placebo group and 19 (18%) in the tranexamic acid group had died (aOR 1·61 [95% CI 0·65 to 3·98])., Interpretation: Intravenous tranexamic acid did not reduce haematoma growth when administered within 2 h of intracerebral haemorrhage symptom onset. There were no observed effects on other imaging endpoints, functional outcome, or safety. Based on our results, tranexamic acid should not be used routinely in primary intracerebral haemorrhage, although results of ongoing phase 3 trials will add further context to these findings., Funding: Australian Government Medical Research Future Fund., Competing Interests: Declaration of interests HZ is a board member of the Pre-hospital Stroke Treatment Organization. GCC has received honoraria from AstraZeneca for lectures and advisory board participation. HM has received honoraria for lectures from the Indonesia Stroke Society Meeting and is the co-chair of the scientific committee for the Asia Pacific Stroke Conference (2024). AM has received consulting fees and participated on an advisory board for Boehringer Ingelheim, and is a member of the board of the World Stroke Organisation. AR has received grants from the Health Research Council of New Zealand, New Zealand Ministry of Health, and Australian and New Zealand Association of Neurologists; participated in a Data Safety Monitoring Board for Argenica Therapeutics; is secretary of the Australia and New Zealand Stroke Organisation; and board member of the World Stroke Organisation and New Zealand Stroke Foundation. VT has received honoraria from Boehringer Ingelheim, Bayer, and Medtronic, and participated in a Data Safety Monitoring Board for EMVision and Itreas. BY has received institutional research grants and honoraria for lectures and conference attendance from Stryker and Medtronic. LMS has received honoraria for lectures and educational materials from Biogen, Pfizer, and AbbVie, and support for conference attendance from Abbott. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Gallbladder cancer (GBC) is a highly malignant and rapidly progressing tumor of the human biliary system, and there is an urgent need to develop new therapeutic targets and modalities. Non-POU domain-containing octamer-binding protein (NONO) is an RNA-binding protein involved in the regulation of transcription, mRNA splicing, and DNA repair. NONO expression is elevated in multiple tumors and can act as an oncogene to promote tumor progression. Here, we found that NONO was highly expressed in GBC and promoted tumor cells growth. The dysregulation of RNA splicing is a molecular feature of almost all tumor types. Accordingly, mRNA-seq and RIP-seq analysis showed that NONO promoted exon6 skipping in DLG1, forming two isomers (DLG1-FL and DLG1-S). Furthermore, lower Percent-Spliced-In (PSI) values of DLG1 were detected in tumor tissue relative to the paraneoplastic tissue, and were associated with poor patient prognosis. Moreover, DLG1-S and DLG1-FL act as tumor promoters and tumor suppressors, respectively, by regulating the YAP1/JUN pathway. N6-methyladenosine (m6A) is the most common and abundant RNA modification involved in alternative splicing processes. We identified an m6A reader, IGF2BP3, which synergizes with NONO to promote exon6 skipping in DLG1 in an m6A-dependent manner. Furthermore, IP/MS results showed that RBM14 was bound to NONO and interfered with NONO-mediated exon6 skipping of DLG1. In addition, IGF2BP3 disrupted the binding of RBM14 to NONO. Overall, our data elucidate the molecular mechanism by which NONO promotes DLG1 exon skipping, providing a basis for new therapeutic targets in GBC treatment., Competing Interests: Declaration of competing interest There are no conflicts of interest to disclose. All authors have seen and approved the manuscript and consent publication., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: There is a growing interest in performing coronary artery and neurovascular interventions via the radial artery; however, few studies have examined the outcomes of transradial carotid stenting. Therefore, our study aimed to compare cerebrovascular outcomes and crossover rates in carotid stenting between transradial and traditional transfemoral approaches., Methods: A systematic review was performed by searching three electronic databases from inception to June 2022 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In addition, random effect meta-analysis was used to pool the odds ratios (ORs) for stroke, transient ischemic attack, major adverse cardiac events, death, major vascular access site complications, and procedure crossover rates between the transradial and transfemoral approaches., Results: A total of 6 studies were included involving a total of n = 567 transradial and n = 6176 transfemoral procedures. The ORs for stroke, transient ischemic attack, and major adverse cardiac events were 1.43 (95% confidence interval, CI 0.72-2.86, I 2  = 0), 0.51 (95% CI 0.17-1.54, I 2  = 0), and 1.08 (95% CI 0.62-1.86, I 2  = 0), respectively. Neither the major vascular access site complication rate (OR 1.11, 95% CI 0.32-3.87, I 2  = 0) nor crossover rate (OR 3.94, 95% CI 0.62-25.11, I 2  = 57%) showed statistically significant differences between the two approaches., Conclusion: The modest quality of the data suggested comparable procedural outcomes between the transradial and transfemoral approaches when performing carotid stenting; however, high level evidence regarding postoperative brain images and risk of stroke in transradial carotid stenting are lacking. Therefore, it is reasonable for interventionists to weigh up the risks of neurological events and potential benefits, including fewer access site complications, before choosing the radial or femoral arteries as access sites. Future large-scale randomized controlled trials are imperative., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Middle meningeal artery embolization (MMAE) for chronic subdural hematoma (CSDH) has gained much attention in recent years. However, unintended embolization may occur when employing liquid embolic agents or particles. We present our clinical experience in simple coiling of MMAE to manage CSDH., Methods: Patients underwent either surgical evacuation or MMAE with simple coiling for CSDH were reviewed. Clinical and radiographic outcomes were assessed at admission, 1-month, and 6-month intervals. Two treatment groups were matched with inverse probability of treatment weighting., Results: One hundred twelve patients were included, with 27 patients in MMAE group and 87 patients in surgery group. In MMAE group, significant reductions were observed in hematoma width (admission vs. 1-month, 2.04 [1.44-2.60] cm vs. 0.62 [0.37-0.95] cm, p  < 0.001). The adjusted odds ratio (aOR) of surgical rescue rate (0.77 95%CI 0.13-4.47, p  = 0.77), hematoma reduction (>50%) (0.21 95%CI 0.04-1.07, p  = 0.06), and midline shift improvement rate (3.22, 95%CI 0.84-12.4, p  = 0.09) had no substantial disparities between two groups at 1-month follow-up. In addition, no significant difference was noted between two groups in terms of hematoma reduction (>50%) at 6-month follow-up (aOR 1.09 95%CI 0.32-3.70, p  = 0.89). No procedure-related complications were found in MMA embolization group., Conclusion: Simple coiling for MMA had comparable outcomes with surgical evacuation for CSDH. Our findings suggest that simple coiling can be an alternative choice for liquid agents or particles in MMA embolization for CSDH with acceptable safety., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: With the development of messenger RNA (mRNA)-based therapeutics for malignant tumor, mRNA vaccines have shown considerable promise for tumor immunotherapy. Immunophenotypes can reflect the tumor microenvironment, which might have a significant influence on the effect of immunotherapy. This study seeks to discover and validate effective antigens that can be employed to develop mRNA vaccines for hepatocellular carcinoma (HCC) and to construct immunophenotypes and immune landscapes to identify potential beneficiaries., Methods: RNA sequencing (RNASeq) data, mutation information, and clinical information were obtained from HCC patients and control cases from The Cancer Genome Atlas - Liver Hepatocellular Carcinoma (TCGA-LIHC), International Cancer Genome Consortium - Liver Cancer (ICGC-LIRI) and Gene Expression Omnibus (GEO) cohorts. Gene Expression Profiling Interactive Analysis (GEPIA2.0), cBioPortal for Cancer Genomics (cBioPortal), Tumor IMmune Estimation Resource (TIMER2.0), and immunohistochemistry (IHC) were employed to discover tumor antigens. ConsensusClusterPlus was employed to perform consistency matrix building and immunophenotypic clustering. Single sample gene set enrichment analysis (ssGSEA), ESTIMATE and monocle2 were employed to map immune cell distribution. Weighted correlation network analysis (WGCNA) was employed to identify potential gene modules that influence the efficacy of mRNA vaccines., Results: Six antigen targets were discovered in the TCGA cohort, including AURKA, CDC25C, KPNA2, MCM3, NEK2 and TUBG1 , which were associated with antigen-presenting cell infiltration and poor prognosis. IHC scores of AURKA, CDC25C and MCM3 were higher in tumor tissues, and high scores of AURKA and CDC25C indicated poor prognosis in the validation cohort. Five immunophenotypes derived from TCGA-LIHC and ICGC-LIRI cohorts were consistent. Furthermore, increased expression of blue and black modules may reduce vaccine responsiveness., Conclusions: AURKA, CDC25C, KPNA2, MCM3, NEK2 and TUBG1 may be potential targets for mRNA vaccine development for HCC, especially AURKA and CDC25C . HCC patients with IS1 and IS5 subtypes perhaps present an autoimmunosuppressed state, then IS2 and IS3 subtypes perhaps the potential beneficiaries., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-1237/coif) and report that the fund supported the experimental parts (reagent purchase, experimental materials, etc.) involved in this manuscript was Basic and Applied Basic Research Foundation of Guangdong Province (Grant No. 2020A1515011379 to He-Yun Zhang). The authors have no other conflicts of interest to declare., (2024 Translational Cancer Research. All rights reserved.)

Consumption of dietary fiber and anthocyanin has been linked to a lower incidence of colorectal cancer (CRC). This study scrutinizes the potential antitumorigenic attributes of a black rice diet (BRD), abundantly rich in dietary fiber and anthocyanin. Our results demonstrate notable antitumorigenic effects in mice on BRD, indicated by a reduction in both the size and number of intestinal tumors and a consequent extension in life span, compared to control diet-fed counterparts. Furthermore, fecal transplants from BRD-fed mice to germ-free mice led to a decrease in colonic cell proliferation, coupled with maintained integrity of the intestinal barrier. The BRD was associated with significant shifts in gut microbiota composition, specifically an augmentation in probiotic strains Bacteroides uniformis and Lactobacillus . Noteworthy changes in gut metabolites were also documented, including the upregulation of indole-3-lactic acid and indole. These metabolites have been identified to stimulate the intestinal aryl hydrocarbon receptor pathway, inhibiting CRC cell proliferation and colorectal tumorigenesis. In summary, these findings propose that a BRD may modulate the progression of intestinal tumors by fostering protective gut microbiota and metabolite profiles. The study accentuates the potential health advantages of whole-grain foods, emphasizing the potential utility of black rice in promoting health., Competing Interests: The authors have declared no competing interests., (© 2024 The Authors. iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.)

Jumping, a fundamental survival behavior observed in organisms, serves as a vital mechanism for adapting to the surrounding environment and overcoming significant obstacles within a given terrain. Here, we present a light-controlled soft jumping actuator inspired by asphondylia, which employs a closed-loop structure and utilizes a liquid crystal elastomer (LCE). Photo-mechanical coupling highlights the significant influence of the light source on the actuator's jumping behavior. Manipulating the light intensity, the relative position of stimulus and light lock, and the concentration of disperse red 1 (DR1) allows precise control over both the maximum take-off velocity and jump height. Furthermore, tailoring the size of the LCE actuator offers a means of regulating jumping behavior. Upon exposure to 460 nm LED irradiation, our actuator achieves remarkable performance, with a maximum jumping height of 10 body length (BL) and take-off velocity of 62 BL/s. These actuators accumulate and rapidly release energy, enabling the effective transportation of microcargos across substantial distances. Our research yields valuable insights into the realm of soft robotics, underscoring the pivotal importance of photo-mechanical coupling in the field of soft robotics, thereby serving as a catalyst for inspiring continued exploration of agile and capable systems by prestoring elastic energy.

Background: Activating signal cointegrator 3 (ASCC3) has been identified as an oncogenic factor that impairs host immune defense. However, the underlying mechanisms of carcinogenesis and its impact on the antitumor immune response remain unclear. In this study, we aimed to investigate the molecular mechanisms of ASCC3 in the progression of non-small cell lung cancer (NSCLC)., Methods: Single-cell sequencing data from the Gene Expression Omnibus and gene expression profiles from The Cancer Genome Atlas database were analyzed. The expression, clinical relevance and biological functions of ASCC3 in NSCLC were explored. Then, RNA sequencing, immunoprecipitation, mass spectrometry, immunofluorescence, and flow cytometry analyses were conducted to explore the underlying molecular mechanisms. In addition, in vivo experiments in mouse models were conducted to explore the probability of ASCC3 knockdown to improve the efficacy of anti-Programmed Death-1 (PD-1) therapy in NSCLC., Results: ASCC3 was significantly upregulated in NSCLC and correlated with poor pathological characteristics and prognosis in patients with NSCLC. Overexpression of ASCC3 promoted malignant phenotypes of NSCLC cells and induced an immunosuppressive tumor microenvironment, which was characterized by a decrease in CD8 + T cells, natural killer cells and dendritic cells but an increase in regulatory T(Treg) cells. Mechanistically, ASCC3 stabilized signal transducer and activator of transcription (STAT)3 signaling by recruiting Cullin-associated and neddylation dissociated 1 (CAND1), which inhibited ubiquitin-mediated degradation of STAT3, thereby impairing the type I interferon response of tumor cells and promoting the immunosuppression and progression of NSCLC. Furthermore, high expression of ASCC3 impaired the efficacy of anti-PD-1 therapy, and an anti-PD-1 antibody combined with ASCC3 knockdown exerted promising synergistic efficacy in a preclinical mouse model., Conclusion: ASCC3 could stabilize the STAT3 pathway via CAND1, reshaping the tumor microenvironment and inducing resistance to anti-PD-1 therapy, which promotes the progression of NSCLC. It is a reliable prognostic indicator and can be a target in combination therapy for NSCLC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Long noncoding RNAs (lncRNAs) are a distinct subtype of RNA that lack protein-coding capacity but exert significant influence on various cellular processes. In non-small cell lung cancer (NSCLC), dysregulated lncRNAs act as either oncogenes or tumor suppressors, contributing to tumorigenesis and tumor progression. LncRNAs directly modulate gene expression, act as competitive endogenous RNAs by interacting with microRNAs or proteins, and associate with RNA binding proteins. Moreover, lncRNAs can reshape the tumor immune microenvironment and influence cellular metabolism, cancer cell stemness, and angiogenesis by engaging various signaling pathways. Notably, lncRNAs have shown great potential as diagnostic or prognostic biomarkers in liquid biopsies and therapeutic strategies for NSCLC. This comprehensive review elucidates the significant roles and diverse mechanisms of lncRNAs in NSCLC. Furthermore, we provide insights into the clinical relevance, current research progress, limitations, innovative research approaches, and future perspectives for targeting lncRNAs in NSCLC. By summarizing the existing knowledge and advancements, we aim to enhance the understanding of the pivotal roles played by lncRNAs in NSCLC and stimulate further research in this field. Ultimately, unraveling the complex network of lncRNA-mediated regulatory mechanisms in NSCLC could potentially lead to the development of novel diagnostic tools and therapeutic strategies., Competing Interests: Declaration of interests The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Restricted tendon gliding is commonly observed in patients after finger flexor tendon (FFT) repair. The study described here was aimed at quantifying the amount of FFT gliding to evaluate the recovery of post-operative tendons using a 2-D radiofrequency (RF)-based ultrasound speckle tracking algorithm (UST)., Methods: Ex vivo uniaxial tensile testing of porcine flexor tendons and in vivo isometric testing of human FFT were implemented to verify the efficacy of UST beforehand. The verified UST was then applied to the patients after FFT repair to compare tendon gliding between affected and healthy sides and to investigate its correlation with the joint range of motion (ROM)., Results: Excellent validity was confirmed with the average R 2 value of 0.98, mean absolute error of 0.15 ± 0.08 mm and mean absolute percentage error of 5.19 ± 2.43% between results from UST and ex vivo testing. The test-retest reliability was verified with good agreement of ICC (0.90). The affected side exhibited less gliding (p = 0.001) and smaller active ROM (p = 0.002) than the healthy side. Meanwhile, a significant correlation between tendon gliding and passive ROM was found only on the healthy side (ρ = 0.711, p = 0.009)., Conclusion: The present study provides a promising protocol to evaluate post-operative tendon recovery by quantifying the amount of FFT gliding with a validated UST. FFT gliding in patients with different levels of ROM restriction should be further explored for categorizing the severity of tendon adhesion., Competing Interests: Conflict of interest The BenQ ultrasound equipment used in this study is a donation from the BenQ Corporation to the College of Medicine, National Taiwan University (July 12, 2018). H.K.W. is a custodian and user of the equipment. There are no potential conflicts of interest among the other authors., (Copyright © 2023 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

There is no strong evidence indicating the optimal treatment for breast cancer (BC) and no specific prognostic model. The aim of this study was to establish nomograms to predict the overall survival (OS) of BC patients receiving chemoradiotherapy and surgery, thereby quantifying survival benefits and improving patient management. A total of 1877 patients with primary nonmetastatic BC who received chemoradiotherapy and surgery from 2010 to 2019 were identified from the Surveillance, Epidemiology and End Results (SEER) database as the training cohort, 804 as the internal validation cohort, and 796 patients from the First Affiliated Hospital of Zhengzhou University (n=324) and Jiaxing Maternal and Child Health Hospital (n=472) as the external validation cohort. Least absolute shrinkage and selection operator (LASSO), univariate, and multivariate Cox regression analyses were performed in the training cohort to determine independent prognostic factors for BC, and a nomogram was constructed to predict 3-year, 5-year, and 8-year OS. The final model incorporated 7 factors that significantly affect OS: race, location, positive regional nodes, T stage, N stage, subtype, and grade. The calibration curves showed good consistency between the predicted survival and actual outcomes. Time-dependent receiver operating characteristic (ROC) curves and the time-dependent area under the curve (AUC) confirmed that the accuracy and clinical usefulness of the constructed nomograms were favorable. Decision curve analysis (DCA) and net reclassification improvement (NRI) also demonstrated that this nomogram was more suitable for clinical use than the 7 th American Joint Committee on Cancer (AJCC) tumor node metastasis (TNM) staging system and the previous prediction model. In the training cohort and the internal validation cohort, the concordance indices (C-index) of the nomogram for predicting OS (0.723 and 0.649, respectively) were greater than those of the 7 th AJCC TNM staging system and the previous prediction model. In addition, based on Kaplan-Meier (K-M) survival curves, the survival differences among different risk stratifications were statistically significant, indicating that our risk model was accurate. In this study, we determined independent prognostic factors for OS in patients with primary nonmetastatic BC treated with chemoradiotherapy and surgery. A new and accurate nomogram for predicting 3-, 5-, and 8-year OS in this patient population was developed and validated for potential clinical applicability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (AJCR Copyright © 2023.)

Background: Rathke's cleft cyst is rare, with variable characteristics and no unified categorization system. This study aimed to evaluate long-term outcomes, based on different categorizations, of symptomatic Rathke's cleft cysts treated with endoscopic endonasal approach., Methods: This retrospective study of 38 patients with symptomatic Rathke's cleft cyst treated with endoscopic endonasal approach from 2006/06-2021/08 recorded pre- and post-operative clinical presentation, endocrine and visual tests, radiological findings, and resection status. Rathke's cleft cysts were categorized by both cyst consistency and radiological features and clinical characteristics were analyzed., Results: The most common pre-operative symptoms were visual field deficit (65.8%) and hypopituitarism (39.5 %). Visual field deficit improved in 84% of affected patients, and hyperprolactinemia improved in 80% of affected patients. Pre-operative hypothyroidism and hypogonadism were associated with radiological type 3 cysts, while headache was more common in type B and C. Type 3 cysts were also associated post-operative hypogonadism and hypothyroidism. Permanent Diabetes insipidus was found in 3 patients (7.9%). Cyst height was a significant factor related to pre-operative visual field deficit and post-operative Diabetes insipidus. Residual cysts were found in 11 cases (30.6%) and 9 patients experienced regrowth/recurrence. Residual cysts were a significant factor in regrowth/recurrence. Recurrence rate and post-operative complications were not correlated with different subtypes., Conclusions: Endoscopic endonasal approach for removal of Rathke's cleft cyst is a safe and effective intervention. It leads to significant improvement in visual field deficit and recovery of hyperprolactinemia. Although the incidence of post-operative Diabetes insipidus is high, it is usually temporary. Although different categorizations are not correlated to recurrence rate, they could help predict the status of hormone deficit., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

This study investigated the effect of Suanzaoren Decoction on the expression of N-methyl-D-aspartate receptors(NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors(AMPAR) in the hippocampus and synaptic plasticity in rats with conditioned fear-induced anxiety. The effect of Suanzaoren Decoction on rat behaviors were evaluated through open field experiment, elevated plus maze experiment, and light/dark box experiment. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of glutamate(Glu) and γ-aminobutyric acid(GABA) in the rat hippocampus. Real-time fluorescence quantitative PCR(qRT-PCR) and Western blot were employed to assess the gene and protein expression of ionotropic glutamate receptors in the hippocampal region. Transmission electron microscopy was utilized to observe the changes in the ultrastructure of synaptic neurons in the hippocampal region. Long-term potentiation(LTP) detection technique was employed to record the changes in population spike(PS) amplitude in the hippocampal region of mice in each group. The behavioral results showed that compared with the model group, the Suanzaoren Decoction group effectively increased the number of entries into open arms, time spent in open arms, percentage of time spent in open arms out of total movement time, number of entries into open arms out of total entries into both arms(P&lt;0.01), and significantly increased the time spent in the light box and the number of shuttle crossings(P&lt;0.01). There was an increasing trend in the number of grid crossings, entries into the center grid, and time spent in the center grid, indicating a significant anxiolytic effect. ELISA results showed that compared with the model group, the Suanzaoren Decoction group exhibited significantly reduced levels of Glu, Glu/GABA ratio(P&lt;0.01), and significantly increased levels of GABA(P&lt;0.01) in the rat hippocampus. Furthermore, Suanzaoren Decoction significantly decreased the gene and protein expression of NMDAR(GluN2B and GluN2A) and AMPAR(GluA1 and GluA2) compared with the model group. Transmission electron microscopy results demonstrated improvements in synapses, neuronal cells, and organelles in the hippocampal region of the Suanzaoren Decoction group compared with the model group. LTP detection results showed a significant increase in the PS amplitude changes in the hippocampal region of Suanzaoren Decoction group from 5 to 35 min compared with the model group(P&lt;0.05, P&lt;0.01). In conclusion, Suanzaoren Decoction exhibits significant anxiolytic effects, which may be attributed to the reduction in NMDAR and AMPAR expression levels and the improvement of synaptic plasticity.

Objective: Adequate brain swelling resolution prior to cranioplasty (CP) is an important yet loosely defined issue. Despite efforts to balance timely CP and patient safety, heterogeneous study methodologies have led to conflicting results. This study aims to standardize this issue through quantifying degree of brain swelling resolution using a proposed Visual CP Scale., Methods: The proposed Visual CP Scale is validated through a 2-pronged approach. The first prong involves a national survey in Taiwan, where neurosurgeons were surveyed to determine what constitutes a patient's readiness for CP. The second prong involves a large retrospective cohort, where the correlations between timing, degree of brain swelling resolution, and post-CP complication rates, are evaluated., Results: In the national Taiwan CP Survey, 124 out of 772 neurosurgeons (17.2%) completed the survey. Respondents who chose higher grades on the Visual CP Scale preferred later CP timings. In the retrospective data, 378 out of 770 (49.1%) patients had pre-CP brain images, allowing for the utilization of the Visual CP Scale. A Visual CP Scale score of greater than or equal to 4 was associated with fewer complications after CP., Conclusions: The timing of CP should be determined by the degree of brain swelling resolution, not vice versa. The proposed Visual CP Scale offers an objective method for assessing brain swelling resolution, making it an adjuvant tool for clinical decision-making and future research related to CP., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: To investigate the musculoskeletal morphomechanical properties (i.e., the thickness and elastic modulus) and the total count of power Doppler signals near the sacroiliac joints in patients with ankylosing spondylitis (AS) and non-AS individuals., Material and Methods: Twenty participants with AS [median age (interquartile range): 31.7 (11.04) years] and 19 controls [36.3 (10.5) years] with no AS history were recruited. Bilateral ultrasound image acquisition was performed, including the short posterior sacroiliac ligament, interosseous sacroiliac ligament, long posterior sacroiliac ligament, iliolumbar ligament, proximal piriformis muscle, and sacrotuberous ligament. The intraclass correlation coefficients (ICC) of ultrasound parameters, laboratory test results of human leukocyte antigen B27, C-reactive protein, and erythrocyte sedimentation rate, and self-reported physical and disease activity scores were also obtained., Results: The ligaments and piriformis muscle were thicker and stiffer (greater elastic modulus) in participants with AS than in non-AS participants (all p<0.01). The measurements showed good or excellent reliability (all ICC(3,1) >0.85). The numbers of power Doppler signals detected in the iliolumbar ligament, proximal piriformis muscle, and sacrotuberous ligament were higher in participants with AS than in non-AS participants (all p<0.001). A correlation was identified between disease duration and the elastic modulus of the piriformis muscle (r=0.640, p=0.003)., Conclusion: We conclude that the ligaments and proximal piriformis muscle of AS participants have increased thickness, elastic modulus, and power Doppler signal than those of non-AS individuals. These reliable findings may serve as potential markers for the early diagnosis of AS and for assessing medication effects.

Evidence indicates that patients with chronic low back pain (CLBP) have lumbar multifidus muscle (LM) activation deficit which might be caused by changes in cortical excitability. Anodal transcranial direct current stimulation (a-tDCS) can be used to restore cortical excitability. This study aimed to (1) determine the immediate effects of a-tDCS on the cortical excitability and LM activation and (2) explore the relationship between cortical excitability and LM activation. Thirteen participants with CLBP during remission and 11 healthy participants were recruited. Cortical excitability (peak-to-peak motor evoked potential amplitude; P2P and cortical silent period; CSP) and LM activation were measured at pre- and post-intervention. We found significant difference (P < 0.05) in P2P between groups. However, no significant differences (P > 0.05) in P2P, CSP and LM activation were found between pre- and post-intervention in CLBP. The CLBP group demonstrated significant correlation (P = 0.05) between P2P and LM activation. Although our finding demonstrates change in P2P in the CLBP group, one-session of a-tDCS cannot induce changes in cortical excitability and LM activation. However, moderate to strong correlation between P2P and LM activation suggests the involvement of cortical level in LM activation deficit. Therefore, non-significant changes could have been due to inadequate dose of a-tDCS., (© 2023. Springer Nature Limited.)

Purpose: The purpose of this study was to investigate the in vivo morphologic features of the cornea in patients with unilateral posterior interstitial keratitis., Methods: Seven eyes of 7 patients with unilateral posterior interstitial keratitis were examined by slit-lamp biomicroscopy, anterior segment optical coherence tomography (AS-OCT), and in vivo confocal microscopy (IVCM). The imaging features of the cornea were evaluated and analyzed., Results: By slit-lamp examination, the posterior corneal stromal opacities were observed in all 7 eyes, and deep neovascularization in 4 eyes. The posterior stromal opacities showed higher reflectivity with an intact overlying epithelium by AS-OCT and did not invade the Bowman's layer in all cases. IVCM revealed highly reflective dispersed microdots, needle-shaped bodies, and increased reflectivity of keratocytes in the lesion site in all patients. Active Langerhans cells and an attenuated subbasal nerve plexus were observed in 5 eyes. After treatment, the active Langerhans cells disappeared; however, highly reflective microdots and needle-shaped bodies remained., Conclusion: The three-dimensional evaluation of slit-lamp biomicroscopy, AS-OCT, and IVCM may help in the early diagnosis of patients with posterior interstitial keratitis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gu, Gao, Wang, He, Peng, Xiao and Hong.)

Few studies have discussed the disease nature and treatment outcomes for bilateral cavernous sinus dural arteriovenous fistula (CSDAVF). This study aimed to investigate the clinical features and treatment outcomes of bilateral CSDAVF. Embase, Medline, and Cochrane library were searched for studies that specified the outcomes of bilateral CSDAVF from inception to April 2022. The classification, clinical presentation, angiographic feature, surgical approach, and treatment outcomes were collected. Meta-analysis was performed using the random effects model. Eight studies reporting 97 patients were included. The clinical presentation was mainly orbital (n = 80), cavernous (n = 52) and cerebral (n = 5) symptoms. The most approached surgical route was inferior petrosal sinus (n = 80), followed by superior orbital vein (n = 10), and alternative approach (n = 7). Clinical symptoms of 88% of the patients (95% CI 80-93%, I 2  = 0%) were cured, and 82% (95% CI 70-90%, I 2  = 7%) had angiographic complete obliteration of fistulas during follow up. The overall complication rate was 18% (95% CI 11-27%, I 2  = 0%). Therefore, endovascular treatment is an effective treatment for bilateral CSDAVF regarding clinical or angiographic outcomes. However, detailed evaluation of preoperative images and comprehensive surgical planning of the approach route are mandatory owing to complexity of the lesions., (© 2023. The Author(s).)

Background: The scavenger receptor CD36 was reported to be highly expressed on tumor-infiltrating CD8 + T cells, but the clinical role remains obscure. This study aims to explore the infiltration and clinical value of CD36 + CD8 + T cells in NSCLC., Methods: Immunohistochemistry and immunofluorescence were conducted for survival analyses and immunological evaluation in 232 NSCLC patients in Zhongshan Hospital. Flow cytometry analyses were carried out to assess the immune cells from fresh tumor samples, non-tumor tissues and peripheral blood. In vitro tumor infiltrating lymphocytes cultures were conducted to test the effect of CD36 blockage., Results: Accumulation of CD36 + CD8 + T cells in tumor tissues was correlated with more advanced stage (p < 0.001), larger tumor size (p < 0.01), and lymph node metastasis (p < 0.0001) in NSCLC. Moreover, high infiltration of CD36 + CD8 + T cells indicated poor prognosis in terms of both overall survival (OS) and recurrence-free survival (RFS) and inferior chemotherapy response. CD36 + CD8 + T cells showed decreased GZMB (p < 0.0001) and IFN-γ (p < 0.001) with elevated PD-1 (p < 0.0001) and TIGIT (p < 0.0001). Analysis of tumor-infiltrating immune cell landscape revealed a positive correlation between CD36 + CD8 + T cells and Tregs (p < 0.01) and M2-polarized macrophages (p < 0.01) but a negative correlation with Th1 (p < 0.05). Notably, inhibition of CD36 partially restored the cytotoxic function of CD8 + T cells by producing more GZMB and IFN-γ., Conclusion: CD36 + CD8 + T cells exhibit impaired immune function and high infiltration of CD36 + CD8 + T cells indicated poor prognosis and inferior chemotherapy response in NSCLC patients. CD36 could be a therapeutic target in combination with chemotherapy in NSCLC patients., (© 2023. The Author(s).)

Immunotherapy has emerged to play a rapidly expanding role in the treatment of cancers. Currently, many clinical trials of therapeutic agents are on ongoing with majority of immune checkpoint inhibitors (ICIs) especially programmed death receptor 1 (PD-1) and its ligand 1 (PD-L1) inhibitors. PD-1 and PD-L1, two main immune checkpoints, are expressed at high levels in thymic epithelial tumors (TETs) and could be predictors of the progression and immunotherapeutic efficacy of TETs. However, despite inspiring efficacy reported in clinical trials and clinical practice, significantly higher incidence of immune-related adverse events (irAEs) than other tumors bring challenges to the administration of ICIs in TETs. To develop safe and effective immunotherapeutic patterns in TETs, understanding the clinical properties of patients, the cellular and molecular mechanisms of immunotherapy and irAEs occurrence are crucial. In this review, the progress of both basic and clinical research on immune checkpoints in TETs, the evidence of therapeutic efficacy and irAEs based on PD-1 /PD-L1 inhibitors in TETs treatment are discussed. Additionally, we highlighted the possible mechanisms underlying irAEs, prevention and management strategies, the insufficiency of current research and some worthy research insights. High PD-1/PD-L1 expression in TETs provides a rationale for ICI use. Completed clinical trials have shown an encouraging efficacy of ICIs, despite the high rate of irAEs. A deeper mechanism understanding at molecular level how ICIs function in TETs and why irAEs occur will help maximize the immunotherapeutic efficacy while minimizing irAEs risks in TET treatment to improve patient prognosis., (© 2023. The Author(s).)

Purpose: The goal was to develop a fully automated grading system for the evaluation of punctate epithelial erosions (PEEs) using deep neural networks., Methods: A fully automated system was developed to detect corneal position and grade staining severity given a corneal fluorescein staining image. The fully automated pipeline consists of the following three steps: a corneal segmentation model extracts corneal area; five image patches are cropped from the staining image based on the five subregions of extracted cornea; a staining grading model predicts a score for each image patch from 0 to 3, and automated grading score for the whole cornea is obtained from 0 to 15. Finally, the clinical grading scores annotated by three ophthalmologists were compared with automated grading scores., Results: For corneal segmentation, the segmentation model achieved an intersection over union of 0.937. For punctate staining grading, the grading model achieved a classification accuracy of 76.5% and an area under the receiver operating characteristic curve of 0.940 (95% CI 0.932 to 0.949). For the fully automated pipeline, Pearson's correlation coefficient between the clinical and automated grading scores was 0.908 (p<0.01). Bland-Altman analysis revealed 95% limits of agreement between the clinical and automated grading scores of between -4.125 and 3.720 (concordance correlation coefficient=0.904). The average time required for processing a single stained image during pipeline was 0.58 s., Conclusion: A fully automated grading system was developed to evaluate PEEs. The grading results may serve as a reference for ophthalmologists in clinical trials and residency training procedures., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) envelope (E) protein forms a pentameric ion channel in the lipid membrane of the endoplasmic reticulum Golgi intermediate compartment (ERGIC) of the infected cell. The cytoplasmic domain of E interacts with host proteins to cause virus pathogenicity and may also mediate virus assembly and budding. To understand the structural basis of these functions, here we investigate the conformation and dynamics of an E protein construct (residues 8-65) that encompasses the transmembrane domain and the majority of the cytoplasmic domain using solid-state NMR. 13 C and 15 N chemical shifts indicate that the cytoplasmic domain adopts a β-sheet-rich conformation that contains three β-strands separated by turns. The five subunits associate into an umbrella-shaped bundle that is attached to the transmembrane helices by a disordered loop. Water-edited NMR spectra indicate that the third β-strand at the C terminus of the protein is well hydrated, indicating that it is at the surface of the β-bundle. The structure of the cytoplasmic domain cannot be uniquely determined from the inter-residue correlations obtained here due to ambiguities in distinguishing intermolecular and intramolecular contacts for a compact pentameric assembly of this small domain. Instead, we present four structural topologies that are consistent with the measured inter-residue contacts. These data indicate that the cytoplasmic domain of the SARS-CoV-2 E protein has a strong propensity to adopt β-sheet conformations when the protein is present at high concentrations in lipid bilayers. The equilibrium between the β-strand conformation and the previously reported α-helical conformation may underlie the multiple functions of E in the host cell and in the virion., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: To explore the effects of Ving Tsun (VT) sticking-hand training on knee joint proprioception and leg muscular performance among community-dwelling middle-aged and older adults., Methods: Thirty-three middle-aged and older adults were randomly assigned to either the VT or control group. The VT group received sticking-hand training twice/week for 3 months. Data were collected before and after the intervention period. The primary outcome was knee joint repositioning error, which was measured using knee joint active repositioning tests. The secondary outcomes included the maximum muscle strength and time to maximum muscle strength of the major leg muscles., Results: No significant group, time, or group-by-time interaction effects were found for the knee joint repositioning error (p > 0.05). The maximum muscle strength of the knee flexors increased over time in the VT group only (p = 0.038). In addition, the time to maximum muscle strength in the hip extensors and flexors increased over time in both groups (p < 0.05). For the knee extensors and flexors, the time to maximum muscle strength increased in the control (p = 0.027) and VT (p = 0.019) groups, respectively, over time., Conclusions: VT sticking-hand training could improve the maximum muscle strength of the knee flexors but could not attenuate the age-related deterioration in leg muscle contraction speed nor improve knee joint proprioception among community-dwelling middle-aged and older adults., Trial Registration: ClinicalTrials.gov NCT03318289. Registered on 23 October 2017., (© 2023. The Author(s).)

Patients with end-stage renal disease (ESRD) are at a higher mortality risk compared with the general population. Previous studies have described a relationship between mortality and patients with ESRD, but the data on standardized mortality ratio (SMR) corresponding to different causes of death in patients undergoing hemodialysis (HD) and peritoneal dialysis (PD) are limited. This study was designed as a nationwide population-based retrospective cohort study. Incident dialysis patients between January 2000 and December 2015 in Taiwan were included. Using data acquired from the Taiwan Death Registry, SMR values were calculated and compared with the overall survival. The results showed there were a total of 128,966 patients enrolled, including 117,376 incident HD patients and 11,590 incident PD patients. It was found that 75,297 patients (58.4%) died during the period of 2000-2017. The overall SMR was 5.21. The neoplasms SMR was 2.11; the endocrine, nutritional, metabolic, and immunity disorders SMR was 13.53; the circulatory system SMR was 4.31; the respiratory system SMR was 2.59; the digestive system SMR was 6.1; and the genitourinary system SMR was 27.22. Therefore, more attention should be paid to these diseases in clinical care.

Background: Multiple perioperative inflammatory markers are considered important factors affecting the long-term survival of esophageal cancer (EC) patients. Hematological parameters, whether single or combined, have high predictive value., Aim: To investigate the inflammatory status of patients with preoperative EC using blood inflammatory markers, and to establish and validate competing risk nomogram prediction models for overall survival (OS) and progression-free survival (PFS) in EC patients., Methods: A total of 508 EC patients who received radical surgery (RS) treatment in The First Affiliated Hospital of Zhengzhou University from August 5, 2013, to May 1, 2019, were enrolled and randomly divided into a training cohort (356 cases) and a validation cohort (152 cases). We performed least absolute shrinkage and selection operator (LASSO)-univariate Cox- multivariate Cox regression analyses to establish nomogram models. The index of concordance (C-index), time-dependent receiver operating characteristic (ROC) curves, time-dependent area under curve (AUC) and calibration curves were used to evaluate the discrimination and calibration of the nomograms, and decision curve analysis (DCA) was used to evaluate the net benefit of the nomograms. The relative integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were calculated to evaluate the improvement in predictive accuracy of our new model compared with the AJCC staging system and another traditional model. Finally, the relationship between systemic inflammatory response markers and prognostic survival was explored according to risk plot, time-dependent AUC, Kaplan-Meier and restricted cubic spline (RCS)., Results: Based on the multivariate analysis for overall survival (OS) in the training cohort, nomograms with 10 variables, including the aggregate index of systemic inflammation (AISI) and lymphocyte-to-monocyte ratio (LMR), were established. Time-dependent ROC, time-dependent AUC, calibration curves, and DCA showed that the 1-, 3-, and 5 year OS and PFS probabilities predicted by the nomograms were consistent with the actual observations. The C-index, NRI, and IDI of the nomograms showed better performance than the AJCC staging system and another prediction model. Moreover, risk plot, time-dependent AUC, and Kaplan-Meier showed that higher AISI scores and lower LMR were associated with poorer prognosis, and there was a nonlinear relationship between them and survival risk., Conclusion: AISI and LMR are easy to obtain, reproducible and minimally invasive prognostic tools that can be used as markers to guide the clinical treatment and prognosis of patients with EC., (© 2023. The Author(s).)

Objective: Ultrasound shear wave elastography is an objective tool to evaluate the stiffness of human tissues. Patients with sialolithiasis could be treated by interventional sialendoscopy with a high success rate. Sialolithiasis could be extracted, and the diseased gland could be preserved and evaluated after treatment. Whether ultrasound shear wave elastography could be used for objective outcome measurement and short-term follow-up of the parenchyma of gland in patients with sialolithiasis remains unclear., Methods: This retrospective self-controlled study was conducted. Patients with sialolithiasis treated by interventional sialendoscopy and followed by high-resolution ultrasound shear wave elastography were selected between January and September 2017., Results: Seventeen patients with sialolithiasis (mean age: 39.63 ± 12.49 years), including 10 women and 7 men, were enrolled. Fifteen patients had sialolithiasis in the submandibular gland and two in the parotid gland. The preoperative value of shear wave velocity was significantly higher in the diseased gland than in the contralateral normal gland ( p  < .001; 95% confidence interval [CI], 0.3915-0.6046). After successful treatment by interventional sialendoscopy surgery, the shear wave velocity of the diseased gland decreased significantly ( p  = 0.001; 95% CI, -0.38792 to -0.20474). However, there was a significant difference between the diseased and contralateral normal glands ( p  = 0.001; 95% CI, 0.0423-0.2895) after 1.55 months of surgery., Conclusion: Ultrasound shear wave elastography could be an adjuvant tool to distinguish sialolithiasis-affected diseased glands from contralateral normal glands and assess the short-term treatment outcome objectively. The changing trend of shear wave velocity could help monitor the healing process of the parenchyma in the diseased gland after treatment., Level of Evidence: 4., Competing Interests: The authors declare no funding, financial relationships, or conflicts of interest related to the subject matter or materials discussed in this article., (© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Gut dysbiosis has been reported in chronic hepatitis B (CHB) infection, however its role in CHB progression and antiviral treatment remains to be clarified. Herein, the present study aimed to characterize gut microbiota (GM) in patients with chronic hepatitis B virus infection-associated liver diseases (HBV-CLD) by combining microbiome with metabolome analyses and to evaluate their effects on peripheral immunity. Fecal samples from HBV-CLD patients (n = 64) and healthy controls (n = 17) were collected for 16s rRNA sequencing. Fecal metabolomics was measured with untargeted liquid chromatography-mass spectrometry in subgroups of 58 subjects. Lineage changes of peripheral blood mononuclear cells (PBMCs) were determined upon exposure to bacterial extracts (BE) from HBV-CLD patients. Integrated analyses of microbiome with metabolome revealed a remarkable shift of gut microbiota and metabolites in HBV-CLD patients, and disease progression and antiviral treatment were found to be two main contributing factors for the shift. Concordant decreases in Turicibacter with 4-hydroxyretinoic acid were detected to be inversely correlated with serum AST levels through host-microbiota-metabolite interaction analysis in cirrhotic patients. Moreover, depletion of E.hallii group with elevated choline was restored in patients with 5-year antiviral treatment. PBMC exposure to BE from non-cirrhotic patients enhanced expansion of T helper 17 cells; however, BE from cirrhotics attenuated T helper 1 cell count. CHB progression and antiviral treatment are two main factors contributing to the compositional shift in microbiome and metabolome of HBV-CLD patients. Peripheral immunity might be an intermediate link in gut microbe-host interplay underlying CHB pathogenesis.

COVID-19 has posed unprecedented challenges to global public health since its outbreak. The Qing-Fei-Pai-Du decoction (QFPDD), a Chinese herbal formula, is widely used in China to treat COVID-19. It exerts an impressive therapeutic effect by inhibiting the progression from mild to critical disease in the clinic. However, the underlying mechanisms remain obscure. Both SARS-CoV-2 and influenza viruses elicit similar pathological processes. Their severe manifestations, such as acute respiratory distress syndrome (ARDS), multiple organ failure (MOF), and viral sepsis, are correlated with the cytokine storm. During flu infection, QFPDD reduced the lung indexes and downregulated the expressions of MCP-1, TNF-[Formula: see text], IL-6, and IL-1[Formula: see text] in broncho-alveolar lavage fluid (BALF), lungs, or serum samples. The infiltration of neutrophils and inflammatory monocytes in lungs was decreased dramatically, and lung injury was ameliorated in QFPDD-treated flu mice. In addition, QFPDD also inhibited the polarization of M1 macrophages and downregulated the expressions of IL-6, TNF-[Formula: see text], MIP-2, MCP-1, and IP-10, while also upregulating the IL-10 expression. The phosphorylated TAK1, IKK[Formula: see text]/[Formula: see text], and I[Formula: see text]B[Formula: see text] and the subsequent translocation of phosphorylated p65 into the nuclei were decreased by QFPDD. These findings indicated that QFPDD reduces the intensity of the cytokine storm by inhibiting the NF-[Formula: see text]B signaling pathway during severe viral infections, thereby providing theoretical and experimental support for its clinical application in respiratory viral infections.

Rationale: Amyloidosis is a group of benign lesions characterized by extracellular deposition of amyloid proteins. Amyloidosis lesions can occur in various organs of the body, but rarely in the urinary system. Amyloidosis in the bladder trigone is extremely rare., Patient Concerns: An 80-year-old female patient presented with painless whole-course gross hematuria with reddish urine and no blood clots, accompanied by right lumbar discomfort., Diagnosis: Based on the patient's medical history and cystoscopy findings, the relevant literature was reviewed and a preoperative diagnosis of bladder tumor was made, although bladder amyloidosis was not excluded. Postoperative pathology ultimately revealed bladder amyloidosis., Interventions: The patient underwent resection of bladder tumor and ureteral stent implantation. Postoperatively, the patient was maintained on antibiotics and oral colchicine treatment., Outcomes: Two months after surgery the patient reported that the gross hematuria had disappeared, and that the right lumbar discomfort was significantly relieved.Cystoscopy showed no obvious recurrence in the operative area, but magnetic resonance imaging (MRI) suggested recurrence. The patient refused partial cystectomy, and the ureteral stent was removed., Lesson: The clinical manifestations of bladder amyloidosis are nonspecific, and under cystoscopy can be easily confused with bladder tumors. Accurate diagnosis of bladder amyloidosis relies on histopathology. Transurethral resection of bladder tumors or partial cystectomy is an option for surgical treatment; the latter should be performed if the ureteral opening is involved., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This study aims to identify potential prognostic and therapeutic biomarkers in papillary renal cell carcinoma (pRCC)., Methods: Two microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified. The protein-protein interaction (PPI) networks and functional annotations of DEGs were established. Survival analysis was utilized to evaluate the prognostic significance of the DEGs and the association between the expression level of candidate biomarkers and various tumour-infiltrating immune cells was explored. The role of PTTG1 in tumour microenvironments (TME) was further explored using Single-cell RNA-seq and its prognostic and therapeutic significance was validated in Fudan University Shanghai Cancer Centre (FUSCC) cohort., Results: Eight genes, including BUB1B , CCNB1 , CCNB2 , MAD2L1 , TTK , CDC20 , PTTG1, and MCM were found to be negatively associated with patients' prognosis. The expression level of PTTG1 was found to be significantly associated with lymphocytes, immunomodulators, and chemokine in the TCGA cohort. Single-cell RNA-seq information indicated that PTTG1 was strongly associated with the proliferation of T cells. In the FUSCC cohort, the expression level of PTTG1 was also statistically significant for both progression-free survival (PFS) and overall survival (OS) prediction (HR = 2.683, p  < .001; HR = 2.673, p  = .001). And higher expression level of PTTG1 was significantly associated with immune checkpoint blockade (ICB) response in the FUSCC cohort ( χ 2 =3.99, p   <   .05)., Conclusions: Eight genes were identified as a prognostic biomarker and the expression level of PTTG1 was also found to serve as a potential predictor for ICB response in pRCC patients.Key messages:Eight genes, including BUB1B , CCNB1 , CCNB2 , MAD2L1 , TTK , CDC20 , PTTG1, and MCM were found to be negatively associated with pRCC patients' prognosis.Expression level of PTTG1 was significantly associated with tumour microenvironment including lymphocytes, immunomodulators, and chemokines.Higher expression level of PTTG1 was significantly associated with immune checkpoint blockade (ICB) response in FUSCC cohort.

Introduction: Stroke remains a leading cause of death worldwide. Stroke in young adults is an important issue, gaining extra attention in recent years. This study aims to investigate the mortality after stroke in young adults in Taiwan., Patients and Methods: This is a registry- and population-based study in Taiwan of patients aged 20-50 years with first-ever stroke between 1999 and 2012, with follow-up until January 1, 2022. Patients and mortalities were identified through Taiwan National Health Insurance database., Results: The study population included 65,097 patients with stroke (mean age, 42.6 ± 6.6 years; 30.5% woman). There were 23,481 (36.1%) intracranial hemorrhage, 37,522 (57.6%) ischemic stroke, and 4094 (6.3%) stroke not otherwise specified. At the end of follow-up, a total of 18,248 deaths (28.0%) occurred during a median follow-up of 9.8 years (interquartile range, 6.4-13.7 years)., Conclusion: Taiwan young adults who were 30-day survivors of first-ever stroke have significantly higher long-term mortality rates when compared to other population-based studies., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© European Stroke Organisation 2022.)

It is usually difficult to achieve good outcomes with salvage treatment for recurrent nasopharyngeal carcinoma (NPC) because of its deep-seated location, surrounding critical structures, and patient history of high-dose irradiation. Gamma Knife radiosurgery (GKS) is a treatment option for malignancies with skull base and intracranial invasion. We conducted a retrospective, observational, single-center study including 15 patients with recurrent NPC (stage T4b) involving the skull base and intracranial invasion, who underwent GKS as a salvage treatment. Patients were enrolled over 12 years. Per a previous study, the TNM classification T4b was subclassified into T4b1 and T4b2, defined as the involvement of the skull base or cavernous sinus with an intracranial extension of <5 mm and >5 mm, respectively. The effect of prognostic factors, including age, sex, survival period, magnetic resonance imaging (MRI) presentation, presence of other distant metastases, tumor volume, marginal dose, maximal dose, and Karnofsky Performance Status (KPS), on outcomes was analyzed. The patients with T4b1 NPC (p = 0.041), small tumor volume (p = 0.012), higher KPS (p < 0.001), and no other metastasis (p = 0.007) had better outcomes after GKS treatment, suggesting that it is a viable treatment modality for NPC. We also suggest that detailed brain imaging studies may enable the early detection of intracranial invasion.

Background: Living donor kidney transplantation (LDKT) is an important organ resource, especially in countries with low deceased donation rates. Strategies for expanding access to transplantation should be developed by identifying the modifiable factors. In this study, we evaluated these factors in the relatives of patients from both medical centers and dialysis clinics using questionnaires., Methods: The questionnaires were anonymous and confidential. We collected questionnaires from previous donors, relatives of patients on the waitlist in the medical center, and relatives of dialysis patients in three nephrology clinics. The study groups were divided into three categories: donor group (n = 68), willing group (n = 43), and non-donor group (n = 65)., Results: Respondents in the clinics had lower cognition and willingness towards LDKT than those in the medical center. More knowledge of LDKT, better relationship with patients, more familial support, and female gender were positively related to donation. The non-donor group tended to want to maintain an intact body for the afterlife. There was no significant difference in age, educational degree, average monthly income, and medical compliance among the three groups., Conclusion: More efforts need to be made in dialysis clinics, where general nephrologists are important for the outreach of information. In addition, dealing with religious ambivalence and reestablishing cultural mindsets with health education programs are important issues in a non-Christian country., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Purpose: Mechanical stimuli are essential for the maintenance of tendon tissue homeostasis. The study aims to elucidate the mechanobiological mechanisms underlying the maintenance of tenocyte homeostasis by cyclic mechanical stretch under high-glucose (HG) condition., Materials and Methods: Primary tenocytes were isolated from rat Achilles tendon and 2D-cultured under HG condition. The in vitro effects of a single bout, 2-h cyclic biaxial stretch session (1 Hz, 8%) on primary rat tenocytes were explored through Flexcell system. Cell viability, tenogenic gene expression, intracellular calcium concentration, focal adhesion kinase (FAK) expression, and signaling pathway activation were analyzed in tenocytes with or without mechanical stretch., Results: Mechanical stretch increased tenocyte proliferation and upregulated early growth response protein 1 (Egr1) expression. An increase in intracellular calcium was observed after 30 min of stretching. Mechanical stretch phosphorylated FAK, calmodulin-dependent protein kinase kinase 2 (CaMKK2), and 5' adenosine monophosphate-activated protein kinase (AMPK) in a time-dependent manner, and these effects were abrogated after blocking intracellular calcium. Inhibition of FAK, CaMKK2, and AMPK downregulated the expression of Egr1. In addition, mechanical stretch reinforced cytoskeletal organization via calcium (Ca2+)/FAK signaling., Conclusions: Our study demonstrated that mechanical stretch-induced calcium influx activated CaMKK2/AMPK signaling and FAK-cytoskeleton reorganization, thereby promoting the expression of Egr1, which may help maintain tendon cell characteristics and homeostasis in the context of diabetic tendinopathy.

Background: Although success was achieved in the therapy for a minority of advanced lung adenocarcinoma (LUAD) patients, anti-programmed death 1 (PD1) resistance was found in most LUAD patients. Here, we aimed to uncover a potential role of exosomal circular RNAs (circRNAs) in LUAD refractory to PD1 blockade.  METHODS: circRNA sequencing and qRT-PCR were performed to determine the level of exosomal circRNAs in LUAD patients subsequently treated with anti-PD1. Then, the RNA pulldown, RNA immunoprecipitation, mass spectrometry, chromatin immunoprecipitation, luciferase reporter assays, flow cytometry, RNA sequencing, and in vitro and in vivo models were used to uncover the biological functions and underlying mechanism of circZNF451 in LUAD anti-PD1 treatment resistance., Results: circRNA sequencing and qRT-PCR identified the up-regulation of exosomal circZNF451 from LUAD patients with progressive disease (PD) compared to those with partial remission (PR) after PD1 blockade therapy. Furthermore, elevated circZNF451 was revealed to be associated with poor prognosis of LUAD patients. Additionally, exosomal circZNF451 was demonstrated to induce an anti-inflammatory phenotype in macrophages and exhaustion of cytotoxic CD8 + T cells, and enhanced TRIM56-mediated degradation of FXR1 to activate the ELF4-IRF4 pathway in macrophages. By transgenic mice, knockout of ELF4 in macrophages was found to rescue immunotherapy efficacy in tumors with high level of exosomal circZNF451., Conclusion: Exosomal circZNF451 reshapes the tumor immune microenvironment by inducing macrophages polarization via the FXR1- ELF4-IRF4 axis and is a novel biomarker for predicting the sensitivity of PD1 blockade in LUAD., (© 2022. The Author(s).)

Background: Previous studies suggested that men with metastatic prostate cancer might benefit from local treatment of the primary tumor., Objective: To determine whether radical local therapy (RLT) improves survival for men with oligometastatic prostate cancer (OMPCa)., Design, Setting, and Participants: This open-label randomized controlled trial included patients with newly diagnosed OMPCa defined as five or fewer bone or extrapelvic lymph node metastases and no visceral metastases., Intervention: Patients were randomly allocated to androgen deprivation therapy (ADT) or ADT and RLT. Men allocated RLT received either cytoreductive radical prostatectomy (RP) or prostate radiation therapy (RT) with a radical dose schedule., Outcome Measurements and Statistical Analysis: The primary outcome was radiographic progression-free survival (rPFS). Secondary outcomes were overall survival (OS) and prostate-specific antigen (PSA) progression-free survival., Results and Limitations: Between September 2015 and March 2019, 200 patients were randomized, with 100 men allocated to each group. The median age was 68 yr and the median PSA at diagnosis was 99 ng/ml. In the study group, 96 patients underwent RLT (85 RP and 11 RT). In the control group, 17 patients eventually received RLT (15 RP and two RT). All patients were included for an intention-to-treat analysis. After a median follow-up of -48 mo, the median rPFS was not reached in the study group and was 40 mo in the control group (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.27-0.70; p = 0.001). The 3-yr OS rate was 88% for the study group and 70% for the control group (HR 0.44, 95% CI 0.24-0.81; p = 0.008)., Conclusions: Men with newly diagnosed OMPCa who received ADT plus RLT (mainly prostatectomy) had significantly higher rates of rPFS and OS than those who received ADT alone., Patient Summary: This study investigated the effect of radical local therapy (RLT) of the primary tumor on survival in patents with oligometastatic prostate cancer. In our group, RLT improved radiographic progression-free and overall survival., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To determine lumbar multifidus (LM) muscle activation deficits in individuals with impaired lumbopelvic control (iLPC) based on musculoskeletal ultrasound in conjunction with electrical stimulation approach and the correlation between back extension force and LM activation., Design: A cross-sectional study design., Setting: A university laboratory., Participants: Fifty participants (25 iLPC and 25 no low back pain [NoLBP]) were recruited from the university physical therapy clinic and surrounding areas., Main Outcome Measures: The musculoskeletal ultrasound was used to measure LM thickness at rest, maximum voluntary isometric contraction (MVIC), and electrical stimulation combined with MVIC, and a handheld dynamometer was used to record force during MVIC and electrical stimulation combined with MVIC. These data were used to derive LM activation (LM ACT ) and percentage force generation (Force GEN )., Results: The iLPC group had significantly lower LM ACT (17%) than the NoLBP group (P<.05). No significant difference was seen in Force GEN between the NoLBP and iLPC groups (P>.05). No significant correlation was seen between LM ACT and Force GEN (P>.05)., Conclusions: The findings support the utility of our protocol to determine LM activation deficits. The lower LM activation in iLPC group suggests that individuals with iLPC were unable to fully recruit the motor units available in LM. Force generation measurements may not be an appropriate approach to determine such deficits in LM., (Copyright © 2022 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Although anti-programmed cell death 1 (PD1) treatment has become a first-line therapy for advanced non-small cell lung cancer (NSCLC), most NSCLC patients are refractory to anti-PD1. Here, we aimed to investigate the mechanism of dysregulated circular RNAs (circRNAs) related to anti-PD1 resistance in NSCLC. The expression of circASCC3 (hsa&#95;circ&#95;0077,495) in NSCLC tissues and cell lines was evaluated by fluorescence in situ hybridization and quantitative reverse transcription-polymerase chain reaction. The functions and mechanisms of circASCC3 in NSCLC progression and anti-PD1 resistance were uncovered in vitro and in vivo. The circASCC3 level was upregulated in NSCLC compared with that in paired normal tissues. Specifically, circASCC3 expression was higher in tissues from NSCLC patients with anti-PD1 refractory than in those from patients who sensitive to anti-PD1. Overexpression of circASCC3 enhanced the malignant phenotype of NSCLC cells and led to an immunosuppressive microenvironment. Mechanistically, circASCC3 sponged miR-432-5p to increase complement C5a levels, which enhanced the progression and dysfunctional immune status of NSCLC. Thus, circASCC3 overexpression reshapes the tumor microenvironment by impacting the complement system in NSCLC and provides a potential strategy to overcome anti-PD1 resistance., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The role of impaired oxygen extraction on peak oxygen uptake ( V ̇ O 2peak ) has been extensively studied using noninvasive and indirect methods in both diabetic patients and healthy participants. Methods: A total of 22 participants with type 2 diabetes mellitus [T2DM; median (range) age: 60 (47-70) years] and 22 controls [58 (52-69) years] with no history of diabetes were recruited (reference no. 201812135RINB). Subjects performed an exhaustive incremental exercise and were evaluated using a gas analyzer and near-infrared spectroscopy (NIRS) to determine V ̇ O 2peak and changes in muscle oxygenation (SmO 2 ) in the vastus lateralis, respectively. Measurements were taken at rest, warm-up, a period during exercise when SmO 2 reached a minimum saturation plateau, and recovery. The microcirculatory responses of the vastus lateralis muscle during incremental exercise in patients with T2DM were compared with those in control individuals, and the correlation between changes in SmO 2 and V ̇ O 2peak was estimated. Results: The diabetic group demonstrated lower V ̇ O 2peak , peak workload, peak heart rate, peak minute ventilation (all P  < 0.05), and lower SmO 2 during the rest, warm-up, and recovery phases (all P  < 0.05) compared with the control group. A correlation was observed between the change in SmO 2 between the warm-up and plateau value and the V ̇ O 2peak ( r  = 0.608, P  = 0.006). Conclusions: The results obtained in this study using NIRS support the feasibility of directly measuring changes in muscle SmO 2 magnitudes to estimate the contributions of peripheral active muscle to systemic O 2 uptake ( V ̇ O 2 ) during incremental exercise.

This paper proposes a network model framework based on long and short-term memory (LSTM) and conditional random field (CRF) to promote Li-ion battery capacity prediction results. The model uses LSTM to extract temporal features from the data and CRF to build a transfer matrix to enhance temporal feature learning for long serialization prediction of lithium battery feature sequence data. The NASA PCOE lithium battery dataset is selected for the experiments, and control tests on LSTM temporal feature extraction modules, including recurrent neural network (RNN), gated recurrent unit (GRU), bi-directional gated recurrent unit (BiGRU) and bi-directional long and short term memory (BiLSTM) networks, are designed to test the adaptability of the CRF method to different temporal feature extraction modules. Compared with previous Li-ion battery capacity prediction methods, the network model framework proposed in this paper achieves better prediction results in terms of root mean square error (RMSE) and mean absolute percentage error (MAPE) metrics., (© 2022. The Author(s).)

This study aimed to systematically evaluate the effect of traditional Chinese medicine(TCM) injections on anthracycline-induced cardiac injury. The Cochrane Library, PubMed, EMbase, CNKI, and other databases were electronically retrieved to gather randomized controlled trials(RCTs) of TCM injections against anthracycline-induced cardiac injury from their inception to September 2021. After two research fellows independently screened the literature and extracted the data, the risk of bias of included RCTs was assessed and network Meta-analysis was performed by R 4.1.0 and Stata 15.1. A total of 50 RCTs were included, involving eight TCM injections. Network Meta-analysis showed that:(1)the combination of anthracyclines with Huachansu Injection might be the optimal treatment to reduce the abnormal electrocardiogram.(2)The combination with Shenfu Injection might be the optimum treatment to ameliorate the left ventricular ejection fraction(LVEF) decrease.(3)The combination with Shenqi Fuzheng Injection might reduce the incidence of cardiotoxicity most satisfactorily.(4)The combination with Xinmailong Injection might improve the elevated cardiac troponin I(cTnI) optimally.(5)The combination with Shenmai Injection might be optimal to control the rise of creatine kinase MB isoenzyme(CK-MB).(6)The combination with Kushen Injection might be the regimen with the lowest gastrointestinal reactions. TCM injections had desirable effect on anthracycline-induced cardiac injury, with low incidence of adverse reactions, and each TCM injection had its own unique advantages. Due to the limitations in quality and methodological conduct of the included studies, more high-level RCTs are needed to validate the conclusions.

The protein tau associates with microtubules to maintain neuronal health. Posttranslational modifications of tau interfere with this binding, leading to tau aggregation in neurodegenerative disorders. Here, we use solid-state nuclear magnetic resonance (NMR) to investigate the structure of the microtubule-binding domain of tau. Wild-type tau that contains four microtubule-binding repeats and a pseudorepeat R' is studied. Complexed with taxol-stabilized microtubules, the immobilized residues exhibit well-resolved two-dimensional spectra that can be assigned to the amino-terminal region of R4 and the R' domain. When tau coassembles with tubulin to form unstable microtubules, the R' signals remain, whereas the R4 signals disappear, indicating that R' remains immobilized, whereas R4 becomes more mobile. Therefore, R' outcompetes the other four repeats to associate with microtubules. These NMR data, together with previous cryo-electron microscopy densities, indicate an extended conformation for microtubule-bound R'. R' contains the largest number of charged residues among all repeats, suggesting that charge-charge interaction drives tau-microtubule association.

Angiogenesis plays the critical roles in promoting tumor progression, aggressiveness, and metastasis. Although few studies have revealed some angiogenesis-related genes (ARGs) could serve as prognosis-related biomarkers for the prostate cancer (PCa), the integrated role of ARGs has not been systematically studied. The RNA-sequencing data and clinical information of prostate adenocarcinoma (PRAD) were downloaded from The Cancer Genome Atlas (TCGA) as discovery dataset. Twenty-three ARGs in total were identified to be correlated with prognosis of PRAD by the univariate Cox regression analysis, and a 19-ARG signature was further developed with significant correlation with the disease-free survival (DFS) of PRAD by the least absolute shrinkage and selection operator (LASSO) Cox regression with tenfold cross-validation. The signature stratified PRAD patients into high- and low-ARGs signature score groups, and those with high ARGs signature score were associated with significantly poorer outcomes (median DFS: 62.71 months vs unreached, p < 0.0001). The predicting ability of ARGs signature was subsequently validated in two independent cohorts of GSE40272 & PRAD&#95;MSKCC. Notably, the 19-ARG signature outperformed the typical clinical features or each involved ARG in predicting the DFS of PRAD. Furthermore, a prognostic nomogram was constructed with three independent prognostic factors, including the ARGs signature, T stage and Gleason score. The predicted results from the nomogram (C-index = 0.799, 95%CI = 0.744-0.854) matched well with the observed outcomes, which was verified by the calibration curves. The values of area under receiver operating characteristic curve (AUC) for DFS at 1-, 3-, 5-year for the nomogram were 0.82, 0.83, and 0.83, respectively, indicating the performance of nomogram model is of reasonably high accuracy and robustness. Moreover, functional enrichment analysis demonstrated the potential targets of E2F targets, G2M checkpoint pathways, and cell cycle pathways to suppress the PRAD progression. Of note, the high-risk PRAD patients were more sensitive to immune therapies, but Treg might hinder benefits from immunotherapies. Additionally, this established tool also could predict response to neoadjuvant androgen deprivation therapy (ADT) and some chemotherapy drugs, such as cisplatin, paclitaxel, and docetaxel, etc. The novel ARGs signature, with prognostic significance, can further promote the application of targeted therapies in different stratifications of PCa patients., (© 2022. The Author(s).)

Introduction: Persistent lymphatic leakage from the surgical drain is a troubling complication occasionally encountered postoperatively. This study investigated lymphatic leaks after renal or liver transplantation, comparing the treatment efficacy of traditional catheter drainage vs. minimally invasive lymphatic interventions. We also discuss access and treatment targets considering the physiology of lymphatic flow., Methods: Between September 2018 and September 2020, 13 patients with lymphatic leakage were treated with minimally invasive lymphatic interventions; 11 had received a renal transplant, and two received a liver transplant. The control group included 10 patients with postrenal transplant lymphatic leakage treated with catheter drainage. The treatment efficacy of catheter drainage, lymphatic interventions, and different targets of embolization were compared., Results: The technical success rate for lymphatic intervention was 100%, and the clinical success rate was 92%, with an 82.9% reduction in drain volume on the first day after treatment. The duration to reach clinical success was 5.9 days with lymphatic intervention, and 33.9 days with conservative catheter drainage., Conclusion: Lymphangiography and embolization are minimally invasive and efficient procedures for treating persistent lymphatic leaks after renal or liver transplantation. We suggest prompt diagnosis and embolization at upstream lymphatics to reduce the duration of drain retention, days of hospitalization, and associated comorbidities., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)