GPC3-targeted CAR-T cells expressing GLUT1 or AGK exhibit enhanced antitumor activity against hepatocellular carcinoma.

Chimeric antigen receptor-expressing T (CAR-T) cells induce robust antitumor responses in patients with hematologic malignancies. However, CAR-T cells exhibit only limited efficacy against solid tumors such as hepatocellular carcinoma (HCC), partially due to their limited expansion and persistence. CD8+ T cells, as key components of the adaptive immune response, play a central role in antitumor immunity. Aerobic glycolysis is the main metabolic feature of activated CD8+ T cells. In the tumor microenvironment, however, the uptake of large amounts of glucose by tumor cells and other immunosuppressive cells can impair the activation of T cells. Only when tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment have a glycolytic advantage might the effector function of T cells be activated. Glucose transporter type 1 (GLUT1) and acylglycerol kinase (AGK) can boost glycolytic metabolism and activate the effector function of CD8+ T cells, respectively. In this study, we generated GPC3-targeted CAR-T cells overexpressing GLUT1 or AGK for the treatment of HCC. GPC3-targeted CAR-T cells overexpressing GLUT1 or AGK specifically and effectively lysed GPC3-positive tumor cells in vitro in an antigen-dependent manner. Furthermore, GLUT1 or AGK overexpression protected CAR-T cells from apoptosis during repeated exposures to tumor cells. Compared with second-generation CAR-T cells, GPC3-targeted CAR-T cells overexpressing GLUT1 or AGK exhibited greater CD8+ T-cell persistence in vivo and better antitumor effects in HCC allograft mouse models. Finally, we revealed that GLUT1 or AGK maintained anti-apoptosis ability in CD8+ T cells via activation of the PI3K/Akt pathway. This finding might identify a therapeutic strategy for advanced HCC.

Application Value of CYFRA21-1 Combined with NSE, CEA, and SCC-Ag in Lung Cancer.

BACKGROUND: This study aims to investigate the application value of serum cytokeratin 19 fragment (CYFRA21-1) combined with nerve-specific enolase (NSE), carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC-Ag) in the diagnosis of lung cancer (LC). METHODS: A total of 831 cases of LC, 360 cases of benign lung disease (BLD) and 102 healthy controls, were enrolled. The data were processed using SPSS, GraphPad Prism, and MedCalc software. RESULTS: The tumor marker (TM) levels in the LC and BLD groups were significantly higher than those in the control group; the CYFRA21-1, NSE, and CEA levels in the patients with LC were higher than in those with BLD. In particular, the increase was predominantly observed for the levels of CEA and CYFRA21-1 in adenocarcinoma (LUAD), CYFRA21-1 and SCC-Ag in squamous cell carcinoma (LUSC), and NSE in small cell carcinoma (SCLC). The CYFRA21-1, NSE, and CEA levels were significantly higher in stage IV than in other stages in LC. Univariate binary logistic analysis showed that increased levels of all four TMs were risk factors for BLD and LC. The area under the curve (AUC) of CYFRA21-1 was most effective in distinguishing patients with BLD or LC from the controls and in distinguishing patients with BLD and LC. The AUCs of combined CYFRA21-1, NSE, and CEA were increased to 0.755, 0.922, and 0.783, respectively, with no significant difference with the AUC of the four combined tests. In the histological classification, the best predictors were CEA, for LUAD, CYFRA21-1 for LUSC, and NSE for SCLC. Moreover, the expression levels of CYFRA21-1, NSE, and CEA significantly decreased after each treatment course. CONCLUSIONS: The combined assay of CYFRA21-1, NSE, and CEA addresses the aspects of accuracy, sensitivity, specificity, and economic cost and should be considered as a potential diagnostic test in LC.

Screening and verification of genes related to polycystic ovary syndrome.

OBJECTIVE: To identify key genes involved in occurrence and development of polycystic ovary syndrome (PCOS). METHODS: By downloading the GSE85932 dataset from the GEO database, we used bioinformatical analysis to analyse differentially expressed genes (DEGs) from blood samples of eight women with PCOS and eight matched controls. Following bioinformatic analysis, we performed a cross-sectional study of serum samples taken from 79 women with PCOS and 36 healthy controls. RESULTS: From the 178 DEGs identified by bioinformatical analysis, 15 genes were identified as significant, and of these, ORM1 and ORM2 were selected for further verification as potential biomarkers for PCOS. Serum ORM1 and ORM2 levels were significantly increased in women with PCOS, and had a high diagnostic value. ORM1 and ORM2 were positively correlated with testosterone, cholesterol, and triglycerides. ORM1 levels were negatively correlated with high density lipoprotein (HDL) while ORM2 levels showed no significant correlation. CONCLUSIONS: ORM may be an effective biomarker for the diagnosis of PCOS and its monitoring may be a useful therapeutic strategy.

[Detection of Fusion Gene and Prognosis Analysis in Children with Acute Lymphoblastic Leukemia of Different Immunophenotypes].

OBJECTIVE: To observe the detection of fusion gene in children with acute lymphoblastic leukemia (ALL) of different immunophenotypes, and analyze the relationship between fusion gene and prognosis. METHODS: The clinical data of 86 children with ALL treated in the hospital from May 2015 to May 2020 were retrospectively analyzed, the immunophenotypes and the prognosis of children were recorded, the detection of fusion gene in ALL children with different immunophenotypes was compared, the relationship between detection of fusion gene and prognosis was analyzed. RESULTS: The results of bone marrow immunophenotype showed that there were 13 cases of T cell type and 73 cases of B cell type in 86 children with ALL. The detection rate of fusion gene SIL-TAL1 in ALL children with T cell type was significantly higher than that in ALL children with B cell type (P<0.05). The detection rates of fusion genes BCR-ABL1, E2A-PBX1 and TEL-AML1 in ALL children with B cell type were higher than those in ALL children with T cell type, but the differences were not statistically significant (P>0.05). Followed up for 8-12 months, recurrence was taken as the end point, the average follow-up time was (10.14±1.75) months, in 86 children with ALL 15 cases recurred (17.44%). The recurrence curve drawn by Kaplan-Meier method showed that the median recurrence time of 15 children with recurrent ALL was 9 months. The proportions of positive minimal residual disease and extramedullary infiltration in the poor prognosis group were higher than those in the good prognosis group, and the differences were statistically significant (P<0.05). The detection rates of fusion genes BCR-ABL and SIL-TAL1 in the poor prognosis group were higher than those in the good prognosis group, and the differences were statistically significant (all P<0.05). Logistic regression analysis showed that positive minimal residual lesions, extramedullary infiltration, and detection of fusion genes BCR-ABL and SIL-TAL1 were risk factors for poor prognosis in children with ALL (OR>1, P<0.05). The ROC curve analysis showed that the area under the curve (AUC) of combined detection of fusion gene BCR-ABL and SIL-TAL1 for predicting the poor prognosis of ALL children was >0.707, which had a certain predictive value. CONCLUSION: There are differences in fusion genes among ALL children with different immunophenotypes, minimal residual disease, extramedullary infiltration, and fusion gene are associated with prognosis of ALL children. Fusion gene detection can be used as new method to predict the prognosis of children with ALL.

Identification of Four Biomarkers of Human Skin Aging by Comprehensive Single Cell Transcriptome, Transcriptome, and Proteomics.

Background: Aging is characterized by the gradual loss of physiological integrity, resulting in impaired function and easier death. This deterioration is a major risk factor for major human pathological diseases, including cancer, diabetes, cardiovascular disease and neurodegenerative diseases. It is very important to find biomarkers that can prevent aging. Methods: Q-Exactive-MS was used for proteomic detection of young and senescence fibroblast. The key senescence-related molecules (SRMs) were identified by integrating transcriptome and proteomics from aging tissue/cells, and the correlation between these differentially expressed genes and well-known aging-related pathways. Next, we validated the expression of these molecules using qPCR, and explored the correlation between them and immune infiltrating cells. Finally, the enriched pathways of the genes significantly related to the four differential genes were identified using the single cell transcriptome. Results: we first combined proteomics and transcriptome to identified four SRMs. Data sets including GSE63577, GSE64553, GSE18876, GSE85358, and qPCR confirmed that ETF1, PLBD2, ASAH1, and MOXD1 were identified as SRMs. Then the correlation between SRMs and aging-related pathways was excavated and verified. Next, we verified the expression of SRMs at the tissue level and qPCR, and explored the correlation between them and immune infiltrating cells. Finally, at the single-cell transcriptome level, we verified their expression and explored the possible pathway by which they lead to aging. Briefly, ETF1 may affect the changes of inflammatory factors such as IL-17, IL-6, and NFKB1 by indirectly regulating the enrichment and differentiation of immune cells. MOXD1 may regulate senescence by affecting the WNT pathway and changing the cell cycle. ASAH1 may affect development and regulate the phenotype of aging by affecting cell cycle-related genes. Conclusion: In general, based on the analysis of proteomics and transcriptome, we identified four SRMs that may affect aging and speculated their possible mechanisms, which provides a new target for preventing aging, especially skin aging.

Antibacterial Activity of Chinese Red Propolis against Staphylococcus aureus and MRSA.

The antibacterial activity of propolis has long been of great interest, and the chemical composition of propolis is directly dependent on its source. We recently obtained a type of propolis from China with a red color. Firstly, the antibacterial properties of this unusual propolis were determined against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). Studies on its composition identified and quantified 14 main polyphenols of Chinese red propolis extracts (RPE); quantification was carried out using liquid chromatography triple quadrupole tandem mass spectrometry (LC-QQQ-MS/MS) and RPE was found to be rich in pinobanksin, pinobanksin-3-acetate, and chrysin. In vitro investigations of its antibacterial activity revealed that its activity against S. aureus and MRSA is due to disruption of the cell wall and cell membrane, which then inhibits bacterial growth. Despite its similar antibacterial activities against S. aureus and MRSA, metabolomic analysis further revealed the effects of RPE on bacteria metabolism were different. The untargeted metabolomic results showed that a total of 7 metabolites in 12 metabolic pathways had significant changes (Fold change > 2, p < 0.05 *) after RPE treatment in S. aureus, while 11 metabolites in 9 metabolic pathways had significant changes (Fold change > 2, p < 0.05 *) after RPE treated on MRSA. Furthermore, RPE downregulated several specific genes related to bacterial biofilm formation, autolysis, cell wall synthesis, and bacterial virulence in MRSA. In conclusion, the data obtained indicate that RPE may be a promising therapeutic agent against S. aureus and MRSA.

Efficacy and safety of non-insulated fractional microneedle radiofrequency for treating difficult-to-treat rosacea: a 48-week, prospective, observational study.

Rosacea is a common chronic facial inflammatory skin disease. However, treatment for "difficult-to-treat rosacea" cases has not been established. This 48-week, prospective, observational study analyzed patients who underwent three non-insulated fractional microneedle radiofrequency (NFMRF) sessions at 2-month intervals. Therapy efficacy, epidermal barrier function, and side effects were evaluated. 34 subjects completed the trial. NFMRF resulted in CEA score reduction from 2.65 ± 0.59 to 1.56 ± 0.50 (P < 0.001) and mean DLQI reduction from 16.70 ± 3.55 to 10.48 ± 2.92 (P < 0.001). The successes of CEA (44.12 vs. 2.94%), IGA (91.67 vs. 25.00%), and flushing (58.82 vs. 26.47%) were observed. Among 34 patients, 22 reported "excellent" or "good" improvement and 30 were "very" or "relatively" satisfied. Skin barrier results revealed that hemoglobin content significantly decreased from 376.47 ± 71.29 at visit 0 to 161.32 ± 52.86 at visit 3. 2 of 30 patients followed-up at 6 months had a relapse at 18 and 20 weeks, respectively. No serious side effects were observed. NFMRF alone results in visible improvement and has great efficacy for difficult-to-treat rosacea without compromising patient safety or damaging the skin barrier.

The association between rosacea and the condition of low tolerance to skincare of the facial skin: a case-control study in China.

BACKGROUND: Patients with rosacea often complained of low tolerance to skincare. AIM: To examine if the preexisted low tolerance to skincare is associated with rosacea the occurrence of the Chinese population. METHODS: A retrospective case-control survey of 997 rosacea cases and 1012 skin-healthy controls was carried out in China. Low tolerance to skincare was evaluated based on the history of facial skin allergic reactions related to skincare in the past 5 years before the onset of rosacea. A comparative analysis was performed between the case and control groups by the chi-square test and the logistic regression analysis. RESULTS: History of facial skin allergic reaction due to skin care products (OR = 5.110, 95% CI = 3.893-6.706) and skin care in beauty salons (OR = 3.002, 95% CI = 1.506-5.981) both presented a positive correlations with the occurrence of rosacea. Facial masks and cosmetics were two of the most common products causing facial allergic reaction. The OR values increased with the increased frequency of allergic reactions related to facial mask and cosmetics. In addition, the history of facial skin allergic reaction had a significantly associated with the severity of self-reported symptoms of rosacea including dryness, burning, stinging and itching. CONCLUSIONS: The condition of low tolerance of the facial skin to skincare was closely associated with the occurrence of rosacea.

Bioinformatics and Network Pharmacology Identify the Therapeutic Role and Potential Mechanism of Melatonin in AD and Rosacea.

Rosacea is significantly associated with dementia, particularly Alzheimer's disease (AD). However, the common underlying molecular mechanism connecting these two diseases remains limited. This study aimed to reveal the common molecular regulatory networks and identify the potential therapeutic drugs for rosacea and AD. There were 747 overlapped DEGs (ol-DEGs) that were detected in AD and rosacea, enriched in inflammation-, metabolism-, and apoptosis-related pathways. Using the TF regulatory network analysis, 37 common TFs and target genes were identified as hub genes. They were used to predict the therapeutic drugs for rosacea and AD using the DGIdb/CMap database. Among the 113 predicted drugs, melatonin (MLT) was co-associated with both RORA and IFN-γ in AD and rosacea. Subsequently, network pharmacology analysis identified 19 pharmacological targets of MLT and demonstrated that MLT could help in treating AD/rosacea partly by modulating inflammatory and vascular signaling pathways. Finally, we verified the therapeutic role and mechanism of MLT on rosacea in vivo and in vitro. We found that MLT treatment significantly improved rosacea-like skin lesion by reducing keratinocyte-mediated inflammatory cytokine secretion and repressing the migration of HUVEC cells. In conclusion, this study contributes to common pathologies shared by rosacea and AD and identified MLT as an effective treatment strategy for rosacea and AD via regulating inflammation and angiogenesis.

Efficacy of non-ablative fractional 1440-nm laser therapy for treatment of facial acne scars in patients with rosacea: a prospective, interventional study.

Acne scarring is one of the most common facial skin disorders. The appropriate treatments for acne scars in patients with rosacea have not been studied. This study was designed to evaluate the efficacy and safety of non-ablative fractional 1440-nm laser (1440-nm NAFL) therapy for treatment of atrophic acne scars in patients with rosacea. In this prospective, interventional study, 32 patients with rosacea and acne scars underwent three sessions of 1440-nm NAFL therapy. Therapy efficacy, epidermal barrier function, and side effects were evaluated. Thirty patients completed and the median acne scar scores significantly reduced from 45 (30, 50) to 15 (15, 30) after three treatments (P < 0.001). The improvement score of acne scars was 2.7 ± 0.7; 22 (73.3%) were satisfied or highly satisfied. The rosacea erythema scores changed from 2.1 ± 0.4 to 1.9 ± 0.5 (P = 0.326), and flushing, burning, and stinging were not worse. The oil content after treatments was significantly reduced (P < 0.001), while there was no significant difference in other indicators of skin barrier function. The quality-of-life score decreased from 17.5 ± 3.8 to 14.1 ± 3.0 (P < 0.001). No serious side effects were observed. The 1440-nm NAFL therapy is effective in the treatment of acne scaring in patients with rosacea with little damage to the skin barrier.

Circular RNA profiling facilitates the diagnosis and prognostic monitoring of breast cancer: A pair-wise meta-analysis.

BACKGROUND: As circular RNAs (circRNAs) have been found to significantly involve in the onset and progression of multiple malignant tumors including breast cancer (BC), this study aims at evaluating the diagnostic and prognostic values of circRNAs in this malady. METHODS: Available databases were thoroughly searched to collect studies on the diagnosis and/or prognosis of BC using circRNA profiling. The updated Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool and the Newcastle Ottawa Scale (NOS) were used to assess the underlying bias of included studies. Clinical characteristics of the studies were merged by the quantitative-weighted integral method to obtain the combined effects. RESULTS: Sixteen studies were included, comprising 2438 BC cases and 271 noncancerous controls. The expression signature covered 24 circRNAs (down-regulated: circ-VRK1, hsa_circ_0068033, hsa_circ_103110, hsa_circ_104689, and hsa_circ_104821; up-regulated: circAGFG1, hsa_circ_0001785, hsa_circ_0108942, hsa_circ_0001785, hsa_circ_006054, hsa_circ_100219, hsa_circ_406697, circEPSTI1, circANKS1B, circGFRA1, circ_0103552, CDR1-AS, has_circ_001569, hsa_circ_001783, circFBXL5, circ_0005230, circAGFG1, circ-UBAP2, and circ_0006528). The sensitivity and specificity of circRNAs in distinguishing BC patients from noncancerous controls were 0.65 and 0.68, and the corresponding area under the curve was 0.66. Survival analysis revealed that patients showing highly expressed oncogenic circRNAs were associated with increased mortality risks of BC in overall survival (univariate analysis: hazard ratio [HR] = 3.30, P = .000; multivariate analysis: HR = 3.07, P = .000), and disease-free survival (HR = 8.26, P = .000). Stratified analysis based on circRNA expression status and control type also showed robust results. CONCLUSIONS: Circular RNA profiling presents prominent diagnostic and prognostic values in BC, and can be rated as a promising tool facilitating its early diagnosis and survival.

Aberrant Expression of Cancer-Testis Antigen FBXO39 in Breast Cancer and its Clinical Significance.

BACKGROUND: Cancer/testis antigen (CTA) is a class of antigen molecules expressed only in the germinal epithelium of testis and some tumor tissues. As an important CTA molecule, the expression of F-box protein 39 (FBXO39) in breast cancer (BC) and its clinical significance remain unclear. The objective of this study is to explore the value of FBXO39 in the diagnosis, efficacy monitoring, and prognostic evaluation of BC. METHODS: The expression of FBXO39 mRNA in the serum exosomes of patients with BC before and after the initial diagnosis and treatment was detected by qRT-PCR, and the corresponding ROC curve was plotted. The expression of FBXO39 protein in BC cancer tissues was detected by immunohistochemistry, along with the analysis of the correlation between FBXO39 expression and clinical pathological features as well as prognosis of BC cases. RESULTS: The serum-derived exosomes were successfully isolated and identified. The positive rate of FBXO39 mRNA in serum exosomes of patients with BC was up to 86%; there was a correlation between the expression level of serum exosomal FBXO39 and clinical staging, HER2, and Ki-67 expression (all with p < 0.05). The sensitivity of serum exosomal FBXO39 in distinguishing BC patients from healthy controls was 88%, with the specificity as 86%, and AUC as 0.9432. The expression change of FBXO39 in serum-sourced exosomes of patients with BC was related to their treatment situation, indicating that the level of FBXO39 decreased significantly after treatment. The expression of FBXO39 in cancer tissue was related to the clinical stage (p = 0.023) and lymphatic metastasis (p = 0.015) of the BC patients. Survival analysis showed that the expression of FBXO39 was negatively correlated with the prognosis of BC patients, with the high expression of FBXO39 indicating poor prognosis. CONCLUSIONS: Serum-derived exosomal FBXO39 could serve as an important indicator of BC diagnosis and efficacy evaluation; FBXO39 could be rated as an important indicator of BC prognosis evaluation.

Purified Vitexin Compound 1 Inhibits UVA-Induced Cellular Senescence in Human Dermal Fibroblasts by Binding Mitogen-Activated Protein Kinase 1.

Purified vitexin compound 1 (VB1), a novel lignanoid isolated from the seeds of the Chinese herb Vitex negundo, has strong antioxidant abilities and broad antitumor activities. However, little is known about its anti-photoaging effect on the skin and the underlying mechanism. Here, we demonstrated that VB1 significantly attenuates ultraviolet A (UVA)-induced senescence in human dermal fibroblasts (HDFs), as evidenced by senescence-associated ß-gal staining, MTT assays, and western blot analysis of the expression of p16 and matrix metalloproteinase-1 (MMP-1). Furthermore, mass spectrometry revealed that VB1 could directly bind to Mitogen-Activated Protein Kinase 1 (MAPK1). Molecular docking and molecular dynamics simulation methods confirmed the mass spectroscopy results and predicted six possible binding amino acids of MAPK1 that most likely interacted with VB1. Subsequent immunoprecipitation analysis, including different MAPK1 mutants, revealed that VB1 directly interacted with the residues, glutamic acid 58 (E58) and arginine 65 (R65) of MAPK1, leading to the partial reversal of UVA-induced senescence in HEK293T cells. Finally, we demonstrated that the topical application of VB1 to the skin of mice significantly reduced photoaging phenotypes in vivo. Collectively, these data demonstrated that VB1 reduces UVA-induced senescence by targeting MAPK1 and alleviates skin photoaging in mice, suggesting that VB1 may be applicable for the prevention and treatment of skin photoaging.

Case Report of Untreated Pediatric Femoral Neck Fracture with Osteopenia.

Pediatric hip fractures are rare. This type of injury often requires surgery within 24 hours to prevent complications such as avascular necrosis, bone non-union, and premature physeal closure. Moreover, chronic disuse from untreated fracture causes severe osteopenia. Untreated pediatric hip fracture is uncommon in the developing world due to access to surgical care. Here, we report a pediatric patient who traveled from Honduras with untreated right femoral neck fracture. The delay in her initial surgical intervention left her with chronic non-union of her right hip joint and significant osteopenia of her right leg secondary to chronic disuse. This patient required a total right hip arthroplasty rather than the conventional internal fixation. It is crucial for emergency physicians to identify the causes of pediatric hip pain. Early detection of these pathologies allows for early orthopedics involvement and surgical intervention to avoid long-term complications. Topics: Pediatric orthopedic, femoral neck fracture, osteopenia.

Diffuse large B-cell lymphoma arising from follicular lymphoma with warthin's tumor of the parotid gland - immunophenotypic and genetic features: A case report.

BACKGROUND: Warthin's tumor (WT) is composed of several cysts that are lined with tall, bilayered oncocytic columnar cells and lymphoid stroma. Within WT, the two components rarely transform into carcinoma or lymphoma, and when it does, carcinoma is the most common type. Approximately 28 cases of lymphoma with WT have been reported, most of which were non-Hodgkin lymphomas, and only a few cases were Hodgkin lymphomas. In the present report, we studied a case of diffuse large B cell lymphoma (DLBCL) arising from follicular lymphoma (FL) with WT in the parotid gland and its immunophenotypic and genetic features. CASE SUMMARY: A 67-year-old man presented with a slowly enlarging right cheek mass for 12 years, and the mass began to change in size over a 2-mo time period. Over time, the patient felt mild local pain and right cheek discomfort. His medical history included a hepatitis B virus infection for 20 years and 30 years of smoking. Gross examination of the excised specimen showed a gray-red and gray-white appearance and a soft texture lobulated external surface neoplasm that measured 9 cm × 8 cm × 7 cm and was well circumscribed by relative normal parotid gland tissue. In cross section, the cut surfaces of the neoplasm were multicystic and had a homogeneous scaly appearance. A small fluid was discovered in the cyst. Bilateral oxyphilic, cuboidal or polygonal epithelium cells and lymphoid intraparenchymal components were observed. Many medium- to large-sized lymphoid cells were observed diffusely in part of the neoplasm, and a few secondary lymphoid follicles were observed at the center or edge of the neoplasm. Immunohistochemical staining showed that the columnar oncocytic cells were positive for AE1/AE3; neoplastic cells located in coarctate follicular were positive for CD20, Pax-5, bcl-2 and bcl-6; and the adjacent diffusely medium- to large-sized lymphoid cells were positive for Pax-5, bcl-6, CD20, MUM-1, bcl-2 and CD79a. The bcl-6 (3q27) break-apart rearrangement was observed, and an Epstein Barr virus test was negative in the tumor cells. The patient survived 6 months after being diagnosed without any treatment. CONCLUSION: WT-associated lymphoma is a very rare neoplasm in the parotid gland. Most cases are B cell non-Hodgkin lymphomas and involve middle-age and older males. This case highlights the extremely rare association of DLBCL arising from FL with WT and the importance of deliberate evaluation of the WT intraparenchymal stroma. Molecular detection techniques have potential advantages in the diagnosis of lymphoma with WT.

Correction: Diagnostic and prognostic utilities of humoral fibulin-3 in malignant pleural mesothelioma: Evidence from a meta-analysis.

[This corrects the article DOI: 10.18632/oncotarget.14712.].

Diagnostic and prognostic utilities of humoral fibulin-3 in malignant pleural mesothelioma: Evidence from a meta-analysis.

Fibulin-3 has emerged as a promising novel biomarker in conforming or monitoring malignant pleural mesothelioma (MPM). This study sought to evaluate the diagnostic and prognostic efficacies of humoral fibulin-3 for MPM. Seven eligible publications comprising 468 MPM cases for diagnosis, and 138 for prognosis were identified. Results manifested that humoral fibulin-3 sustained a pooled sensitivity of 0.62 (95% CI: 0.45-0.77) and specificity of 0.82 (95% CI: 0.73-0.89) in discriminating MPM patients from cancer-free individuals, corresponding to an AUC (area under the curve) of 0.81. For the survival analysis, fibulin-3 expression was not markedly associated with overall survival (OS) time of the MPM patients [HR (hazard ratio): 1.84, 95% CI: 0.75-4.56, P = 0.185]. In the subgroup analyses stratified by test matrix and ethnicity, data revealed that serum-based fibulin-3 examination achieved superior accuracy than plasma-based analysis (sensitivity: 0.77 versus 0.54; specificity: 0.85 versus 0.77; AUC: 0.92 versus 0.69); additionally, testing of fibulin-3 in Europeans retained higher efficacy than those in Americans and Australians. Taken together, fibulin-3 confers a relatively high diagnostic efficacy and is acceptable to be an auxiliary biomarker to aid in MPM identification.

[The Role of Hydrogen Sulfide in Acute Liver Injury Induced by Traumatic Stress in Rats].

OBJECTIVE: To explore the role of hydrogen sulfide (H2S) in acute liver injury induced by crushing hind limbs of rats. METHODS: The rats were randomly divided into the following groups: control, crushing, H2S donor sodium hydrosulfide (NaHS) + crushing, H2S inhibitor propargylglycine (PAG) + crushing group. The acute liver injury model was established by 'crushing the hind limbs of rats with standard weight. Rats were sacrificed at 30 min and 120 min after the crush. The activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured by colorimetric method, and the content of H2S in plasma and the contents of malondialdehyde (MDA), protein carbonyl, glutathione (GSH) in the liver and the activity of H2S generating enzyme (cystathionine y-lyase, CSE) were determined by chemical method. The expression of CSE mRNA in liver was detected by RT-PCR. RESULTS: For crush injury group, the levels of AST and ALT in serum, MDA and protein carbonyl in liver increased. The levels of GSH, CSE, CSE mRNA in liver and H2S in serum decreased. The administration of NaHS before limbs crush could attenuate the changes of liver injury, but the pre-treatment with PAG could exacerbate the changes. CONCLUSION: The decrease of H2S production could involve in mediating the acute liver injury induced by traumatic stress in rats.

[The Risk Factors of Contralateral Central Lymph Node Metastasis in Solitary Thyroid Papillary Micro-carcinoma].

OBJECTIVE: To explore the possible risk factors of contralateral central lymph node metastasis (CLNM) in solitary thyroid papillary micro-carcinoma (PTMC). METHODS: Clinicopathologic data of 318 patients with confirmed solitary PTMC by final histological who underwent bilateral centeral lymph node dissection (CLND) from April 2012 to May 2015 in our hospital were retrospectively reviewed. Univariate Χ2 test and multivariate logistic regression analysis were used to determine the risk factors of contralateral CLNM in solitary PTMC. RESULTS: The incidence of ipsilateral CLNM and contralateral CLNM in solitary PTMC patients were 40.57% (129/318), 9.75% (31/318), respectively. Univariate analyses revealed that contralateral CLNM had a correlation with tumor located in lower pole, capsular invasionand underlying ipsilateral CLNM (P < 0.05), and had a correlation with underlying nodular goiter (P < 0.05). Multivariate logistic regression analysis showed that tumor located in lower pole and ipsilateral CLNM were independent risk factors for contralateral CLNM (P < 0.05). CONCLUSIONS: Solitary PTMC patients had a low tendency to contralateral CLNM, it shouldn't undergo contralateral CLND commonly, if the tumor located in lower pole or combine withipsilateral CLNM, it should be consider to undergo bilateral CLND.

Radiation-induced expression of IER5 is dose-dependent and not associated with the clinical outcomes of radiotherapy in cervical cancer.

This study aimed to investigate the expression of the immediate-early response 5 (IER5) gene in cervical cancer tissues and explore the association between the expression of IER5 and the clinical outcomes of radiotherapy. We collected specimens by surgery or biopsy and obtained 53 specimens from tissues after radiotherapy and 16 specimens from tissues before radiotherapy. Immunohistochemistry and western blotting were used to assess the protein expression levels of IER5. Quantitative polymerase chain reaction (qPCR) was performed to assess the mRNA expression levels of IER5. The protein and mRNA expression levels of IER5 in cervical cancer patients treated with radiation doses ≥20 Gy were significantly higher than in those treated with radiation doses <20 Gy (P<0.05) and before treatment with radiotherapy. Moreover, the expression of IER5 was significantly positively correlated with the radiation dose (immunohistochemistry: r=0.548, P=0.019; qPCR: r=0.671, P=0.002; western blotting: r=0.573, P<0.0001). Radiotherapy induced the upregulated expression of IER5 and this was dependent on the radiation dose. However, the radiation-induced expression of IER5 was not associated with the clinical outcomes of radiotherapy in cervical cancer.