Non­coding RNA: A promising diagnostic biomarker and therapeutic target for esophageal squamous cell carcinoma (Review).

Esophageal cancer (EC) is a common form of malignant tumor in the digestive system that is classified into two types: Esophageal squamous cell carcinomas (ESCC) and esophageal adenocarcinoma. ESCC is known for its early onset of symptoms, which can be difficult to identify, as well as its rapid progression and tendency to develop drug resistance to chemotherapy and radiotherapy. These factors contribute to the high incidence of disease and low cure rate. Therefore, a diagnostic biomarker and therapeutic target need to be identified for ESCC. Non-coding RNAs (ncRNAs) are a class of molecules that are transcribed from DNA but do not encode proteins. Initially, ncRNAs were considered to be non-functional segments generated during transcription. However, with advancements in high-throughput sequencing technologies in recent years, ncRNAs have been associated with poor prognosis, drug resistance and progression of ESCC. The present study provides a comprehensive overview of the biogenesis, characteristics and functions of ncRNAs, particularly focusing on microRNA, long ncRNAs and circular RNAs. Furthermore, the ncRNAs that could potentially be used as diagnostic biomarkers and therapeutic targets for ESCC are summarized to highlight their application value and prospects in ESCC.

Valvar bypass surgery to ameliorate persistent lower limb edema caused by post-thrombotic syndrome: a case report and literature review.

Obstruction and/or reflux compromise during venous emptying can facilitate different pathophysiologies in chronic venous insufficiency (CVI). We present a patient with persistent lower limb CVI edema caused by post-thrombotic syndrome (PTS), who responded well to femoral vein valve therapy via axillary vein bypass after unsuccessful valvuloplasty, and led a normal life. During a 12 month observation period, bridging vessels completely restored original anatomical structures. In a literature study, no similar surgeries were reported, but we show that this operation may be feasible in selected patients.

Molecular engineering of AIE-active boron clustoluminogens for enhanced boron neutron capture therapy.

The development of boron delivery agents bearing an imaging capability is crucial for boron neutron capture therapy (BNCT), yet it has been rarely explored. Here we present a new type of boron delivery agent that integrates aggregation-induced emission (AIE)-active imaging and a carborane cluster for the first time. In doing so, the new boron delivery agents have been rationally designed by incorporating a high boron content unit of a carborane cluster, an erlotinib targeting unit towards lung cancer cells, and a donor-acceptor type AIE unit bearing naphthalimide. The new boron delivery agents demonstrate both excellent AIE properties for imaging purposes and highly selective accumulation in tumors. For example, at a boron delivery agent dose of 15 mg kg-1, the boron amount reaches over 20 µg g-1, and both tumor/blood (T/B) and tumor/normal cell (T/N) ratios reach 20-30 times higher than those required by BNCT. The neutron irradiation experiments demonstrate highly efficient tumor growth suppression without any observable physical tissue damage and abnormal behavior in vivo. This study not only expands the application scopes of both AIE-active molecules and boron clusters, but also provides a new molecular engineering strategy for a deep-penetrating cancer therapeutic protocol based on BNCT.

A new strategy for intervertebral disc regeneration: The synergistic potential of mesenchymal stem cells and their extracellular vesicles with hydrogel scaffolds.

Intervertebral disc degeneration (IDD) is a disease that severely affects spinal health and is prevalent worldwide. Mesenchymal stem cells (MSCs) and their derived extracellular vesicles (EVs) have regenerative potential and have emerged as promising therapeutic tools for treating degenerative discs. However, challenges such as the harsh microenvironment of degenerated intervertebral discs and EVs' limited stability and efficacy have hindered their clinical application. In recent years, hydrogels have attracted much attention in the field of IDD therapy because they can mimic the physiologic microenvironment of the disc and provide a potential solution by providing a suitable growth environment for MSCs and EVs. This review introduced the biological properties of MSCs and their derived EVs, summarized the research on the application of MSCs and EVs in IDD, summarized the current clinical trial studies of MSCs and EVs, and also explored the mechanism of action of MSCs and EVs in intervertebral discs. In addition, plenty of research elaborated on the mechanism of action of different classified hydrogels in tissue engineering, the synergistic effect of MSCs and EVs in promoting intervertebral disc regeneration, and their wide application in treating IDD. Finally, the challenges and problems still faced by hydrogel-loaded MSCs and EVs in the treatment of IDD are summarized, and potential solutions are proposed. This paper outlines the synergistic effects of MSCs and EVs in treating IDD in combination with hydrogels and aims to provide theoretical references for future related studies.

Synthesis and Characterization of Zinc/Iron Composite Oxide Heterojunction Porous Anode Materials for High-Performance Lithium-Ion Batteries.

Environmental pollution caused by the use of fossil fuels is becoming increasingly serious, necessitating the adoption of clean energy solutions. Lithium-ion batteries (LIBs) have attracted great attention due to their high energy density and currently occupy a dominant commercial position. Metal oxide materials have emerged as promising anode materials for the next generation of LIBs, thanks to their high theoretical capacity. However, the practical application of these materials is hindered by their substantial volume expansion during lithium storage and poor electrical conductivity. In this work, a zinc/iron bimetallic hybrid oxide composite, ZnO/ZnFe2O4/NC, is prepared using ZIF-8 as a precursor (ZIF-8, one of the metal organic frameworks). The N-doped porous carbon composite improves the volume change and optimizes the lithium-ion and electron transport. Meanwhile, the ZnFe2O4 and ZnO synergistically enhance the electrochemical activity of the anode through the built-in heterojunction to promote the reaction kinetics at the interface. As a result, the material delivers an excellent cycling performance of 604.7 mAh g-1 even after 300 cycles of 1000 mA g-1. This study may provide a rational design for the heterostructure and doping engineering of anodes for high-performance lithium-ion batteries.

Influence of Martensite/Bainite Dual Phase-Content on the Mechanical Properties of EA4T High-Speed Axle Steel.

In this work, we have investigated the effect of martensite/bainite dual phase content on the mechanical properties of EA4T high-speed axle steel. For evaluation and control of the strength, ductility, and toughness of steel, the microstructure of lath martensite (LM) and granular bainite (GB) was clarified through an optical microscope (OM), electron backscatter diffraction (EBSD), and transmission electron microscopy (TEM). Besides, the tensile fracture morphology was studied by scanning electron microscopy (SEM). For this purpose, this study conducted a quantitative analysis of the LM and GB fractions using the Pro Imaging software-2018 of OM. The remarkable effect of the LM/GB structure on mechanical properties is discussed. The results have shown that by increasing the volume fraction of the GB structure, the LM structure is refined and its microhardness and strength are improved. Meanwhile, the micro strength of LM follows the Hall-Petch relationship with the lath martensite packet size. Subsequently, the mechanical property prediction model of EA4T steel based on the LM/GB content was established by regression analysis of all experiment dates. When the LM fraction in the steel is about 40-70%, a superior combination of strength, ductility, and toughness can be obtained in EA4T steel.

Prognostic factors in patients with thymoma who underwent surgery.

PURPOSE: Thymoma is the most common primary tumor in the anterior mediastinum. The prognostic factors of patients with thymoma still need to be clarified. In this study, we aimed to investigate the prognostic factors of patients with thymoma who received radical resection and establish the nomogram to predict the prognosis of these patients. MATERIALS AND METHODS: Patients who underwent radical resection for thymoma with complete follow-up data between 2005 and 2021 were enrolled. Their clinicopathological characteristics and treatment methods were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify the independent prognostic factors. According to the results of the univariate analysis in the Cox regression model, the predictive nomograms were created. RESULTS: A total of 137 patients with thymoma were enrolled. With a median follow-up of 52 months, the 5-year and 10-year PFS rates were 79.5% and 68.1%, respectively. The 5-year and 10-year OS rates were 88.4% and 73.1%, respectively. Smoking status (P = 0.022) and tumor size (P = 0.039) were identified as independent prognostic factors for PFS. Multivariate analysis showed that a high level of neutrophils (P = 0.040) was independently associated with OS. The nomogram showed that the World Health Organization (WHO) histological classification contributed more to the risk of recurrence than other factors. Neutrophil count was the most important predictor of OS in patients with thymoma. CONCLUSION: Smoking status and tumor size are risk factors for PFS in patients with thymoma. A high level of neutrophils is an independent prognostic factor for OS. The nomograms developed in this study accurately predict PFS and OS rates at 5 and 10 years in patients with thymoma based on individual characteristics.

LncRNA WAC-AS1 expression in human tumors correlates with immune infiltration and affects prognosis.

BACKGROUND: WAC-antisense RNA1 (WAC-AS1) is a newly identified long non-coding RNA (lncRNA) implicated in the prognosis and development of a few types of tumors. However, the correlations of WAC-AS1 with immune infiltration and patient prognosis in pan-cancer remain unclear. In the present study, we aimed to investigate the prognostic value and immunological functions of WAC-AS1 across 33 different types of cancers. METHODS: To investigate the potential oncogenic roles of WAC-AS1, bioinformatics analyses were performed using the Cancer Genome Atlas (TCGA) and Genotype Tissue-Expression (GTEx) datasets. The correlations of WAC-AS1 with prognosis, clinical phenotype, tumor mutational burden (TMB), microsatellite instability (MSI), tumor regulation-related genes, tumor microenvironment, immune cell infiltration, and drug resistance to commonly used chemotherapy drugs in different types of tumors were explored. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed to explore the biological functions of WAC-AS1 in tumors. In situ hybridization (ISH) was performed in tissue microarray (TMA) to confirm the expression of WAC-AS1 in multiple tumor tissues. RESULTS: WAC-AS1 showed aberrant expression in most cancers when compared to the normal tissues. It also has prognostic value in multiple types of cancers. Elevated WAC-AS1 expression was associated with poor prognosis and overall survival in adrenocortical carcinoma (ACC), breast invasive carcinoma (BRCA), and liver hepatocellular carcinoma (LIHC). A significant negative correlation between WAC-AS1 expression and overall survival was observed in brain lower-grade glioma (LGG), pancreatic adenocarcinoma (PAAD), and skin cutaneous melanoma (SKCM). The expression of WAC-AS1 also showed a correlation with clinical stage in six types of tumors, and with tumor mutational burden and microsatellite instability in several different types of cancers. The immune scores of those cancers were found to be significant. Additionally, the effectiveness of fluorouracil and four other anticancer drugs was significantly different based on the expression of WAC-AS1 in these cancers. Moreover, the ISH results showed in six types of tumors, the expression of WAC-AS1 was consistent with the Pan-cancer analysis using TCGA and GTEx database. CONCLUSIONS: These results indicate an intensive involvement of WAC-AS1 in the regulation of immune responses, immune cell infiltration, and malignant properties in various types of cancers, suggesting that WAC-AS1 may serve as a prognostic marker across diverse types of cancers.

Silencing UBQLN2 Enhances the Radiosensitivity of Esophageal Squamous Cell Carcinoma (ESCC) via Activating p38 MAPK.

Background: Ubiquilin 2 (UBQLN2) is an adaptor of ubiquitinated proteins and the proteasome. The potential role of UBQLN2 in carcinogenesis has been demonstrated. However, its role in modulating the radiosensitivity of cancer is not clear. Here, we explored the radiosensitizing effect of silencing UBQLN2 on esophageal squamous cell carcinoma (ESCC) and its mechanisms. Methods: We analyzed the prognostic role of UBQLN2 in the ESCC patient cohort from the Cancer Genomic Atlas (TCGA) database and our hospital. We also conducted a series of experiments in vivo and in vitro to investigate the effect of silencing UBQLN2 on ESCC radiosensitivity and its mechanisms. Results: UBQLN2 is highly expressed in ESCC tissues and positively correlated with poor overall survival (OS). The knockdown of UBQLN2 dramatically increased the radiosensitivity of ESCC cells. Mechanically, UBQLN2 suppression substantially upregulated p38 mitogen-activated protein kinases (MAPK). The p38 MAPK inhibitor SB203580 could reverse the radiation-enhancing effect induced by UBQLN2 knockdown. The direct interaction between UBQLN2 and p38 MAPK was confirmed by co-immunoprecipitation (CO-IP) assay. Furthermore, silencing UBQLN2 also inhibited the expression of phosphorylated DNA-dependent protein kinase catalytic subunit (p-DNA-PKcs) after irradiation. Finally, the xenografted tumor experiment confirmed the radiosensitizing effect of silencing UBQLN2 on ESCC in vivo. Conclusion: Our results suggest that silencing UBQLN2 enhances the radiosensitivity of ESCC by activating p38 MAPK, and UBQLN2 may be a potential target to enhance the radiosensitivity of ESCC.

Recall of reactive cutaneous capillary endothelial proliferation (RCCEP) induced by stereotactic body radiation therapy (SBRT) in a patient with lung squamous cell carcinoma.

Camrelizumab (SHR-1210) is a humanized IgG4 monoclonal anti-programmed cell death protein 1 (PD-1) antibody that has been shown to inhibit the binding of PD-1 to PD-L1, thereby blocking the immune escape of various types of cancer, including lung squamous cell carcinoma (LSCC). Reactive cutaneous capillary endothelial proliferation (RCCEP) is the most common adverse event in camrelizumab-treated patients. Here, we introduce a case of LSCC with recall RCCEP induced by stereotactic body radiation therapy (SBRT). A 76-year-old LSCC patient developed RCCEP when he received camrelizumab and chemotherapy. After discontinuing camrelizumab treatment, the RCCEP lesions spontaneously regressed and fell off. However, when the patient received subsequent SBRT, the RCCEP occurred again at the same sites. This case may provide clues for additional study of the immune reactivation effect of SBRT or the underlying mechanism of RCCEP.

Integrated 18F-FDG PET/CT parameter defines metabolic oligometastatic non-small cell lung cancer.

AIMS: The purpose of this study was to define metabolic oligometastatic non-small cell lung cancer (NSCLC) by using the number of metastatic lesions and 18F-FDG PET/CT parameters. METHODS: One hundred twenty-four newly diagnosed stage IV NSCLC patients who received pretreatment 18F-FDG PET/CT examination were retrospectively analyzed. The maximum standardized uptake value (SUVmax) of primary and metastatic lesions and the collected clinical parameters were fed into the univariate and multivariate Cox proportional hazard model. Survival analysis was performed using Kaplan-Meier and log-rank test. RESULTS: In univariate analysis, the results revealed that histology, metastatic organ numbers, adrenal gland metastasis, SUVmax of both primary and metastatic lesions, lactate dehydrogenase, systemic treatment, and local treatment were significantly correlated with overall survival of stage IV NSCLC patients. Multivariate analysis demonstrated that SUVmax of primary lesions and systemic treatment were independent risk factors of stage IV NSCLC patients. The addition of primary lung cancer SUVmax to traditional method (only count the numbers of metastasis lesions) enhanced the identification of oligometastatic NSCLC and the C-index increased from 0.601 to 0.693. CONCLUSION: We developed a method for the definition of metabolic oligometastatic NSCLC, which combined the number of organs involved, the number of metastatic lesions, and the SUVmax of primary lung cancer.

Changes in Patellar Morphology Following Soft Tissue Surgical Correction of Recurrent Patellar Dislocation in Children with Low-Grade Trochlear Dysplasia.

OBJECTIVE: To investigate the changes in patellar morphology following soft tissue surgical correction of recurrent patellar dislocation in children with low-grade trochlear dysplasia. METHODS: The prospective cohort study was performed between November 2007 and December 2012. Finally, 25 cases, with the mean age of 8.4 years (range from 7 to 10 years), were admitted to the study. All patients were diagnosed as bilateral recurrent patellar dislocation associated with femoral trochlear dysplasia. The knee that suffered injury or was dislocated was treated with medial patellar retinacular plasty (surgery group). The contralateral knee, which served as a control, was treated conservatively (conservative group). Axial CT scans were undertaken in all patients to assess the patellar morphological characteristics. RESULTS: The mean follow-up time was 60.8 months (range 48 to 75 months). Preoperatively, there were no statistically significant differences between the patellar morphology in the two groups (P > 0.05). Many radiological parameters of patellar morphology were significantly different between the two groups at the final follow-up, including well-known parameters, such as the mean patellar width (surgery group, 40.58 mm [SD 1.26]; conservative group, 36.41 mm [SD 1.17]; P < 0.05), the mean patellar thickness (surgery group, 11.59 mm [SD 0.74]; conservative group, 9.38 mm [SD 0.56]; P < 0.05) and the mean Wiberg index (surgery group, 0.54 [SD 0.06]; conservative group, 0.72 [SD 0.08]; P < 0.05). There are also little-known parameters, such as the ratio of length of lateral patella to medial patella (surgery group, 1.26 [SD 0.17]; conservative group, 1.69 [SD 0.21]; P < 0.05), which was a measurement of facet asymmetry. However, the Wiberg angle was not significantly different between the two groups (surgery group, 128.63° [SD 9.05]; conservative group, 125.47° [SD 13.96°]; P > 0.05) at the final follow-up. No complications were found. CONCLUSIONS: The patellar morphology can be significantly improved by early soft tissue surgical correction in children with patellar instability associated with low-grade femoral trochlear dysplasia.

CDK4/6 inhibitor enhances the radiosensitization of esophageal squamous cell carcinoma (ESCC) by activating autophagy signaling via the suppression of mTOR.

OBJECTIVE: To investigate the radiosensitizing effect of cyclin D-cyclin dependent kinase (CDK) 4/6 inhibitor palbociclib on esophageal squamous cell carcinoma (ESCC) and its underlying mechanisms. METHODS: The effect of palbociclib on ESCC cell radiosensitivity was detected by cell counting kit-8 (CCK-8) and clonogenic assay. γH2AX immunofluorescent staining was used to assess the repair of DNA damage induced by radiation. The expression of DNA repair proteins were examined by western blotting. Subsequently, immunoblotting and autophagy inhibitors were used to evaluate the underlying mechanisms of palbociclib triggered radiosensitization. Finally, the xenografts of ESCC were established to study the radiosensitizing effect of palbociclib in vivo. RESULTS: Palbociclib combined with irradiation significantly inhibited the cell viability of ESCC in vitro. The expression level of γH2AX showed that radiation induced DNA damage repair was inhibited by palbociclib treatment. Palbociclib also suppressed the expression of RAD51 and phosphorylated DNA-dependent protein kinase catalytic subunit (p-DNA-PKcs) after irradiation. Mechanically, palbociclib enhanced the radiosensitization of ESCC by activating autophagy via suppression of mammalian target of rapamycin (mTOR). Inhibition of autophagy using chloroquine could partially reverse the radiation enhancing effect of palbociclib. Lastly, the xenografted tumor experiment confirmed the radiosensitizing effect of palbociclib in ESCC in vivo. CONCLUSION: Our results showed that palbociclib improved the radiosensitivity of ESCC in vivo and in vitro, and thus it may be a promising radiosensitization agent for the treatment of ESCC.

Clinical characteristics and patient outcomes of molecular subtypes of small cell lung cancer (SCLC).

BACKGROUND: Recent studies have shown that according to the expression levels of achaete-scute homolog 1 (ASCL1), neurogenic differentiation factor 1 (NEUROD1), and POU class 2 homeobox 3 (POU2F3), small cell lung cancer (SCLC) can be divided into four subtypes: SCLC-A (ASCL1-dominant), SCLC-N (NEUROD1-dominant), SCLC-P (POU2F3-dominant), and SCLC-I (triple negative or SCLC-inflamed). However, there are limited data on the clinical characteristics and prognosis of molecular subtypes of SCLC. METHODS: Immunohistochemistry (IHC) was used to detect the expression levels of ASCL1, NEUROD1, and POU2F3 in 53 patient samples of resectable SCLC. The subtype was defined by the differential expression of the transcription factors for ASCL1, NEUROD1, and POU2F3 or the low expression of all three factors with an inflamed gene signature (SCLC-A, SCLC-N, SCLC-P, and SCLC-I, respectively). The clinicopathological characteristics, immunological features (programmed death ligand 1 [PD-L1] expression and CD8+ tumor infiltrating lymphocyte [TIL] density), and patient outcomes of the four subtypes of SCLC were analyzed. RESULTS: Positive ASCL1, NEUROD1, and POU2F3 staining was detected in 43 (79.2%), 27 (51.0%), and 17 (32.1%) SCLC specimens by IHC. According to the results of IHC analysis, SCLC was divided into four subtypes: SCLC-A (39.6%), SCLC-N (28.3%), SCLC-P (17.0%), and SCLC-I (15.1%). The 5-year overall survival (OS) rates of these four subtypes were 61.9%, 69.3%, 41.7%, and 85.7%, respectively (P=0.251). There were significant differences in smoking status among different subtypes of SCLC (P= 0.031). However, we did not confirm the correlation between subtypes of SCLC and other clinicopathological factors or immune profiles. Cox multivariate analysis showed that N stage (P=0.025), CD8+ TILs (P=0.024), Ki-67 level (P=0.040), and SCLC-P (P=0.023) were independent prognostic factors for resectable SCLC. CONCLUSIONS: Our IHC-based study validated the proposed classification of SCLC using the expression patterns of key transcriptional regulatory factors. We found that SCLC-P was associated with smokers and was one of the poor prognostic factors of limited-stage SCLC. In addition, no correlation was found between PD-L1 expression or CD8+ TIL density and SCLC subtypes.

Transposition Mucosal Flap Combined With Autologous Fat Transplantation to Repair Lip Defects Caused by Sclerotherapy of Hemangioma.

ABSTRACT: Infantile hemangiomas are the most common benign childhood tumors and can occur on any part of the human body. Sclerosing agents are used in the early stage of treatment of infantile hemangioma. Sometimes a lip defect remains after sclerosing agent treatment. We developed a simple technique to repair lip defects. The authors performed transposition mucosal flap and autologous fat transplantation surgery on patients who had lip defects caused by sclerosing agents. The flap was transposed 90° from the intraoral labial mucosa to the vermilion defect. Autologous fat was transplanted to the white lip defect. If necessary, a secondary fat transplantation may be performed every half year. All patients were followed up to evaluate the effect of the operation. Patients were asked to rate their satisfaction with the surgery between 1 and 10. Digital three-dimensional evaluation was performed. Sixteen patients underwent the surgery successfully, and the flaps were all viable. No complications occurred after surgery (5 males, 11 females; age range, 5-27 years; 12 upper lip, 3 lower lip, and 1 median lip). The patients were satisfied with the aesthetic outcome of surgery (mean score, 9). Seven patients wanted to undergo a second fat transplantation, whereas 9 patients felt it was unnecessary to transplant fat again. Transposition mucosal flap combined with autologous fat transplantation is reliable and minimally invasive. It is an effective method for repairing moderate lip defects mainly involving vermilion caused by a sclerosing agent.

A Cell Cycle Progression-Derived Gene Signature to Predict Prognosis and Therapeutic Response in Hepatocellular Carcinoma.

OBJECTIVE: Dysregulation of cell cycle progression (CCP) is one of the hallmarks of cancer. Here, our study is aimed at developing a CCP-derived gene signature for predicting high-risk population of hepatocellular carcinoma (HCC). METHODS: Our study retrospectively analyzed the transcriptome profiling and clinical information of HCC patients from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) projects. Uni- and multivariate cox regression models were conducted for identifying which hallmarks of cancer were risk factors of HCC. CCP-derived gene signature was developed with LASSO method. The predictive efficacy was verified by ROC curves and subgroup analyses. A nomogram was then generated and validated by ROC, calibration, and decisive curves. Immune cell infiltration was estimated with ssGSEA method. Potential small molecular compounds were predicted via CTRP and CMap analyses. The response to chemotherapeutic agents was evaluated based on the GDSC project. RESULTS: Among hallmarks of cancer, CCP was identified as a dominant risk factor for HCC prognosis. CCP-derived gene signature displayed the favorable predictive efficacy in HCC prognosis independent of other clinicopathological parameters. A nomogram was generated for optimizing risk stratification and quantifying risk evaluation. CCP-derived signature was in relation to immune cell infiltration, HLA, and immune checkpoint expression. Combining CTRP and CMap analyses, fluvastatin was identified as a promising therapeutic agent against HCC. Furthermore, CCP-derived signature might be applied for predicting the response to doxorubicin and gemcitabine. CONCLUSION: Collectively, CCP-derived gene signature was a promising marker in prediction of survival outcomes and therapeutic responses for HCC patients.

The role of the deubiquitinating enzyme DUB3/USP17 in cancer: a narrative review.

The balance between ubiquitination and deubiquitination is critical for the degradation, transport, localization, and activity of proteins. Deubiquitinating enzymes (DUBs) greatly contribute to the balance of ubiquitination and deubiquitination, and they have been widely studied due to their fundamental role in cancer. DUB3/ubiquitin-specific protease 17 (USP17) is a type of DUB that has attracted much attention in cancer research. In this review, we summarize the biological functions and regulatory mechanisms of USP17 in central nervous system, head and neck, thoracic, breast, gastrointestinal, genitourinary, and gynecologic cancers as well as bone and soft tissue sarcomas, and we provide new insights into how USP17 can be used in the management of cancer.

Phlegmasia Cerulea Dolens in the Upper Extremity: A Case Report and Literature Review.

Phlegmasia cerulea dolens (PCD) is a rare condition characterized by deep venous thrombosis with gangrene. It can result in critically severe edema that affects the blood supply to the limbs. PCD generally occurs in the lower rather than upper extremity. We herein present a case report of upper extremity PCD and discuss thrombophilia secondary to low protein S activity as the main cause. Catheter-directed thrombolysis via the occluded end of the artery may be one of the best treatment methods for PCD.

Potential health risks of inhaled toxic elements and risk sources during different COVID-19 lockdown stages in Linfen, China.

Levels of toxic elements in ambient PM2.5 were measured from 29 October 2019 to 30 March 2020 in Linfen, China, to assess the health risks they posed and to identify critical risk sources during different periods of the COVID-19 lockdown and haze episodes using positive matrix factorization (PMF) and a health-risk assessment model. The mean PM2.5 concentration during the study period was 145 µg/m3, and the 10 investigated toxic elements accounted for 0.31% of the PM2.5 mass. The total non-cancer risk (HI) and total cancer risk (TCR) of the selected toxic elements exceed the US EPA limits for children and adults. The HI for children was 2.3 times that for adults for all periods, which is likely due to the high inhalation rate per unit body weight for children. While the TCR for adults was 1.7 times that of children, which is mainly attributed to potential longer exposure duration for adults. The HI and TCR of the toxic elements during full lockdown were reduced by 66% and 58%, respectively, compared to their pre-lockdown levels. The HI and TCR were primarily attributable to Mn and As, respectively. Health risks during haze episodes were significantly higher than the average levels during COVID-19 lockdowns, though the HI and TCR of the selected toxic elements during full-lockdown haze episodes were 68% and 17% lower, respectively, than were the levels during pre-lockdown haze episodes. During the study period, fugitive dust and steel-related smelting were the highest contributors to HI and TCR, respectively, and decreased in these emission sources contributed the most to the lower health risks observed during the full lockdown. There, the control of these sources is critical to effectively reduce public health risks.