Association of Serum Potassium Variability With 60-day Mortality and Cardiovascular Events after COVID-19 Infection in Maintenance Hemodialysis Patients.

Objective: This study aimed to investigate the association between serum potassium variability and 60-day mortality and cardiovascular disease (CVD) in maintenance hemodialysis (MHD) patients following the coronavirus disease 2019 (COVID-19) infection. Methods: We conducted a retrospective study on MHD patients treated at the affiliated hospital of Qingdao University hemodialysis center who were infected with the novel coronavirus between December 1, 2022, and January 31, 2023. Baseline characteristics of patients were collected from electronic medical records. Kaplan-Meier survival analysis was used to obtain patient survival probabilities, and multivariate Cox hazard regression models and binary Logistic regression models were used to obtain hazard ratios (HR), odds ratios (OR), and 95% confidence intervals (95% CI) between exposure and outcomes. Results: A total of 296 patients were included in this study, with a mean age of 57.2±16.3 years, and 59.8% were male. The 60-day mortality rate was 10.8%, and the incidence of CVD was 32.8%. Kaplan-Meier curves showed that a higher potassium variability coefficient was associated with higher all-cause mortality (P = 0.024). After adjusting for potential confounders, multivariate Cox regression analysis showed that the HR for 60-day mortality in the Q4 group compared to the Q1 group was 2.06 (95% CI = 1.03-4.09, P = 0.040), and binary Logistic regression analysis showed that the OR for 60-day CVD in the Q4 group compared to the Q1 group was 4.09 (95% CI = 1.52-10.97, P = 0.005). Conclusion: Increased serum potassium variability in MHD patients after COVID-19 infection significantly increased the likelihood of 60-day mortality and CVD.

Proteomic profiling identifies novel diagnostic biomarkers and molecular subtypes for mucinous tubular and spindle cell carcinoma of the kidney.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a relatively rare renal epithelial neoplasm resembling type 1 papillary renal cell carcinoma (PRCC) morphologically and immunohistochemically. The accurate diagnosis of MTSCC remains a challenge. Here, by using proteomic profiling, we characterized MTSCC and PRCC to identify diagnostic biomarkers. We found that the MTSCC tumor proteome was significantly enriched in B-cell-mediated immunity when compared with the proteome of adjacent normal tissues of MTSCC or tumors of PRCC. Importantly, we identified MZB1, VCAN, and SOSTDC1 as diagnostic biomarkers to distinguish MTSCC from the solid variant of type 1 PRCC, with an AUC of 0.985 when combined. MZB1 was inversely correlated with tumor clinical stage and may play an anti-tumor role by activating the complement system. Finally, unsupervised clustering revealed two molecular subtypes of MTSCC, displaying different morphology, expression signatures of oxidative phosphorylation, and aggravation. In summary, our analyses identified a three-protein diagnostic panel and molecular subtypes for MTSCC. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Retracted: Targeting Transforming Growth Factor-Beta1 (TGF-ß1) Inhibits Tumorigenesis of Anaplastic Thyroid Carcinoma Cells Through ERK1/2-NFκB-PUMA Signaling.

The in vitro experiments of TGF-ß1 and the results of RT-PCR could not be repeated. In order not to affect others, the authors have asked for a retraction. Reference: Qiang Yin, Shan Liu, Anbing Dong, Xiufang Mi, Fengyun Hao, Kejun Zhang. Targeting Transforming Growth Factor-Beta1 (TGF-ß1) Inhibits Tumorigenesis of Anaplastic Thyroid Carcinoma Cells Through ERK1/2-NFkappakB-PUMA Signaling. Med Sci Monit 2016; 22: 2267-2277. DOI: 10.12659/MSM.898702.

Regulation of GSK3ß/Nrf2 signaling pathway modulated erastin-induced ferroptosis in breast cancer.

Ferroptosis is a newly discovered form of regulated cell death and characterized by an iron-dependent accumulation of lethal lipid reactive oxygen species (ROS), ferroptosis may exhibit a novel spectrum of clinical activity for cancer therapy. However, the significance of ferroptosis in the context of carcinoma biology is still emerging. Glycogen synthase kinase-3ß (GSK-3ß) has been found to be a fundamental element in weaking antioxidant cell defense by adjusting the nuclear factor erythroid 2-related factor 2 (Nrf2). In our study, decreased expression of GSK-3ß was observed in the cancer tissues of breast cancer patients, results of immunohistochemistry indicated that Nrf2 was highly expressed in low-GSK-3ß-expressed breast cancer tissues. The contributions of aberrant expression of GSK-3ß and Nrf2 to the erastin-induced ferroptosis in breast cancer were further assessed, silence of GSK-3ß blocked erastin-induced ferroptosis with less production of ROS and malondialdehyde (MDA) via upregulation of GPX4 and downregulation of arachidonate 15-lipoxygenase (Alox15), overexpression of GSK-3ß enhanced erastin-triggered ferroptosis with elevated ROS and MDA. Enhanced erastin-induced ferroptosis by overexpression of GSK-3ß was blocked by activating Nrf2. We further confirmed that overexpression of GSK-3ß strengthened erastin-induced tumor growth inhibition in breast cancer xenograft models in vivo. In summary, our findings conclude that modulation the balance between GSK-3ß/Nrf2 is a promising therapeutic approach and probably will be important targets to enhance the effect of erastin-induced ferroptosis in breast cancer.

Clusterin Reduces Cold Ischemia-Reperfusion Injury in Heart Transplantation Through Regulation of NF-kB Signaling and Bax/Bcl-xL Expression.

BACKGROUND/AIMS: Ischemia-reperfusion (I/R) injury is an unavoidable event occurring during heart transplantation and is a key factor in graft failure and the long-term survival rate of recipients. Therefore, there is an urgent need for the development of new therapies to prevent I/R injury. Clusterin is a hetero-dimeric glycoprotein with an antiapoptotic function. In this study, we investigated whether clusterin was cardioprotective in heart transplantation against I/R injury using an in vivo rat model and an in vitro cell culture system, and examined the underlying mechanisms of I/R injury. METHODS: Heart grafts from wild-type C57BL/6 mice were preserved in UW solution (control) or UW solution containing recombinant human apolipoprotein-J (hr clusterin) for 24 h. The preserved hearts were implanted into recipient mice of the same strain as the donors for 72 h, and the heart grafts were then taken for histopathological and gene expression analyses. An in vitro ischemia reperfusion model using H9C2 cells or H9C2/clusterin cDNA cells was constructed. The expression of clusterin, p65, Bax, Bcl-xL, IL-1ß, and TNF-α protein and mRNA in heart tissue and H9C2 cells was detected by western blot, reverse transcription-polymerase chain reaction (RT-PCR), and quantitative RT-PCR assays; IL-1ß and TNF-α protein was detected by enzyme-linked immunosorbent assays; NF-kB activity was detected by an electrophoretic mobility shift assay; cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and flow cytometric analyses. RESULTS: Cold I/R caused severe morphologic myocardial injury to heart grafts from wild-type C57BL/6 mice, whereas grafts from hr clusterin preservation showed less damage, as demonstrated by decreased cell apoptosis/death, decreased neutrophil infiltration, and the preservation of the normal structure of the heart. Clusterin reduced the expression of p65, pre-inflammatory IL-1ß, and TNF-α, and the pro-apoptotic gene Bax, while it enhanced the expression of the anti-apoptotic gene Bcl-xL in vitro and in vivo. Clusterin inhibited cell apoptosis/death and reduced pre-inflammatory. CONCLUSION: Clusterin is a promising target for preventing cold I/R injury in heart transplantation. This study also shows that the resultant protective effects of clusterin are mediated by NF-κB signaling and Bax/Bcl-xL expression.

S100A4 Knockout Sensitizes Anaplastic Thyroid Carcinoma Cells Harboring BRAFV600E/Mt to Vemurafenib.

BACKGROUND/AIMS: Anaplastic thyroid cancer (ATC), with 25% BRAFV600E mutation, is one of the most lethal human malignancies that currently has no effective therapy. Vemurafenib, a BRAFV600E inhibitor, has shown promise in clinical trials, including ATC patients, but is being hampered by the acquisition of drug resistance. Therefore, combination therapy that includes BRAFV600E inhibition and avoids resistance is a clinical need. METHODS: ATC cell lines 8505C (BRAFV600E/mt), SW1736 (BRAFV600E/mt), KAT18 (BRAFV600E/wt) and Cal-62(BRAFV600E/wt) cells were used in the study. The ability of S100A knockout or /and in combination with the BRAF inhibitor vemurafenib on growth, apoptosis, invasion and apoptosis in ATC cells in vitro was demonstrated by MTT and BrdUrd incorporation assay, Annexin-V-FITC staining analyzed by flow cytometry, Transwell migration and Matrigel invasion assay. S100A4,pERK1/2, pAKT and pROCK1/2 protein was detected by western blot assay; Small molecule inhibitors of Y27632, U0126, MK-2206 and constitutively active forms of pCDNA-Myc-pERK, pCMV6-HA-Akt, pCMV-RhoA were employed, and the mechanistic studies were performed. We assessed the efficiency of in vivo combination treatment with S100A4 knockout and Vemurafenib on tumors. RESULTS: S100A4 knockout induced apoptosis and reduced proliferation by inactivation of pAKT and pERK signals, and inhibited invasion and migration by inactivation of pAKT and RhoA/ROCK1/2 signals in 8505C or Cal-62 cells in vitro, and vice versa in SW1736 and KAT18 cells. Vemurafenib did not affect apoptosis of both 8505C and SW1736 cells, but reduced proliferation via arresting cell cycle, and promoted cell migration and invasion in vitro. Combination treatment with S100A4 knockdown and vemurafenib reduced cell proliferation, migration and invasion in vitro compared to the S100A4 knockdown or Vemurafenib alone. Vemurafenib treatment resulted in a transient inhibition of pERK expression and gradually activation of pAKT expression, but quickly recovery from ERK1/2 activation inhibition by vemurafenib treatment in 4 h for SW1736 and 8505C cells. Combined treatment completely inhibited ERK1/2 and AKT activation during 48 h. In an in vivo mouse model of SW1736 and 8505C, vemurafenib treatment alone did not significantly inhibit tumor growth in both of the tumors, but inhibited tumor growth in combined groups. CONCLUSION: Our results show S100A4 knockout alone inhibits ATC cells (rich endogenous S100A4) survival and invasion, regardless of the BRAFV600E status, and potentiates the effect of vemurafenib on tumor regression in vitro and in vivo. In addition, S100A4 knockout potently inhibits the recovery from ERK1/2 activation inhibition and the AKT activation following vemurafenib treatment and reversed the vemurafenib resistance. This therapeutic combination may be of benefit in patients with ATC.

Targeting Transforming Growth Factor-Beta1 (TGF-ß1) Inhibits Tumorigenesis of Anaplastic Thyroid Carcinoma Cells Through ERK1/2-NFκkB-PUMA Signaling.

BACKGROUND The transforming growth factor-beta (TGF-ß) signaling pathway plays a critical role in promoting tumor growth. TGF-ß1was found to be overexpressed in anaplastic thyroid cancer (ATC). We therefore tested our hypothesis that targeting TGF-ß1 inhibits tumorigenesis of ATC cells. MATERIAL AND METHODS Effects of TGF-ß1 stimulation or TGF-ß1 inhibition by small interfering RNA (TGF-ß1siRNA) on proliferation, colony formation, and apoptosis in 8505C cells in vitro was detected using siRNAs and inhibitors to examine the TGF-ß1 signaling pathway. A subcutaneously implanted tumor model of 8505C cells in nude mice was used to assess the effects of TGF-ß1 inhibition on tumorigenesis development. RESULTS TGF-ß1siRNAs decreased proliferation and colony formation, and increased apoptosis in 8505C cells in vitro and inhibited tumor growth in vivo. TGF-ß1siRNA inhibited phosphorylation ERK1/2 (pERK1/2) and increased p65-dependant PUMA mRNA and protein expression. Knockdown of p65 or PUMA by siRNA reduced TGF-ß1siRNA-induced apoptosis, as well as caspase-3 and PARP activation. Upregulation of p65 or PUMA expression by TGF-ß1siRNA requires pERK1/2 inhibition. TGF-ß1 shRNA inhibited tumor growth in vivo. CONCLUSIONS Therapies targeting the TGF-ß1 pathway may be more effective to prevent primary tumor formation. The ability of this therapy to decrease tumorigenesis may be related to ERK1/2/NF-κB/PUMA signaling.

Cervical lymph node thyroglobulin measurement in washout of fine-needle aspirates for diagnosis of papillary thyroid cancer metastases.

BACKGROUND: Patients with papillary thyroid cancer (PTC) and enlarged cervical lymph nodes (CLNs) are usually assessed by fine-needle aspiration biopsy cytology (FNAB-C). Thyroglobulin (Tg) is frequently detected in washout of fine-needle aspirates (FNA) of these lymph nodes. The aim of this study was to evaluate the accuracy of the measurement of FNAB-Tg in the washout of FNAB in combination with FNAB-C to detect CLN metastases in PTC. METHODS: We retrospectively evaluated 163 surgically proven CLNs. Ultrasound-guided FNAB-C and FNAB-Tg measurements were performed and the ultrasound features were evaluated. RESULTS: The sensitivity, specificity and accuracy of FNAB-C, FNAB-Tg and FNAB-C/FNAB-Tg in diagnosis of metastatic CLNs were 85.7, 87.8 and 71.6%, were 80.5, 87 and 82.8% and were 97.1, 96.3 and 95.7%, respectively. The diagnostic sensitivity, specificity and accuracy of FNAB-C/FNAB-Tg for metastatic CLNs was significantly higher than that of FNAB-C or FNAB-Tg alone (p < 0.01). CONCLUSION: Combined US-guided FNAB-C and FNAB-Tg can improve the accuracy for diagnosis of metastatic CLNs in patients with PTC.

Fine needle aspiration cytology for lymph nodes: a three-year study.

BACKGROUND AND AIMS: The cytologic patterns of lymph node fine needle aspirations (FNAs) exhibit a wide variation in different diseases and in different ethnic groups in various geographical locations. Knowledge of lymphadenopathy patterns in a given geographical region is essential for making a confident diagnosis of suspected disease in that location. In the present study, we assessed the cytologic patterns of lymph node aspirations in patients in the Huangdao region of China. METHODS: A three-year retrospective study design was conducted on FNA cytology samples from the lymph nodes of patients in our hospital between January 2011 and December 2014. RESULTS: A total of 2136 lymph nodes were aspirated during the study period. Cytologic analysis of the lymph nodes revealed the following: malignancy, 53.6%; chronic non-specific lymphadenitis, 15.2%; reactive lymph node, 7.5%; pyogenic abscess, 2.9%; tuberculosis lymphadenitis, 8.7%; Hodgkin lymphoma, 4.8%; and non-Hodgkin lymphoma, 7.16%. The 30-50 year age group was the most affected age group, while lymphadenopathy in the >60 year age group was less frequent. Cervical lymph nodes were the most frequent site for lymphadenopathy in women (31.4%, p < 0.001) and men (49.1%, p < 0.001). CONCLUSIONS: Lymphadenopathy is associated with a wide range of disorders; however, metastatic lymph nodes of malignancies are the most common cause for enlarged lymph nodes.

pERK1/2 silencing sensitizes pancreatic cancer BXPC-3 cell to gemcitabine-induced apoptosis via regulating Bax and Bcl-2 expression.

BACKGROUND: Our previous study has demonstrated that knockdown of activated ERK1/2(pERK1/2) sensitizes pancreatic cancer cells to chemotherapeutic drug gemcitabine (Gem) treatment. However, the details of this survival mechanism remain undefined. It has also shown that Bcl-2 confers resistance and Bax sensitizes to gemcitabine-induced apoptosis in pancreatic cancer cells. Furthermore, the extracellular signaling-regulated kinase (ERK) signaling pathway regulates Bcl-2/Bax expression ratio. We therefore tested the hypothesis that pancreatic cancer cells are resistant to gemcitabine and this resistance is due to activation of ERK1/2 and subsequent upregulation of Bcl-2 and downregulation of Bax. METHODS: Pancreatic cancer cell BXPC-3 was used in the study. The effect of pharmacological inhibition of ERK1/2 on resistance of pancreatic cancer cells to apoptosis induced by treatment with gemcitabine was analyzed. The following methods were utilized: TUNEL and ELISA were used to detect apoptosis. Western blot was used to detect the protein expression. RESULTS: Gemcitabine treatment enhanced the activity of ERK1/2 in the BXPC-3 cells. Inhibition of the ERK1/2 by PD98059 could downregulate Bcl-2 and upregulate Bax and was associated with restoration of sensitivity to gemcitabine in BXPC-3 cells. Depletion of endogenous Bcl-2 expression by specific small interfering RNA transfection significantly increased gemcitabine-induced cell apoptosis. Combined treatment with PD98059 and Bax siRNA transfection could decrease gemcitabine-induced ERK1/2 and Bax activation, which subsequently resulted in decreased apoptosis. CONCLUSIONS: The upregulation of ERK1/2-dependent Bcl-2 and downregulation of ERK1/2-dependent Bax can protect human pancreatic cancer cells from gemcitabine-induced apoptosis. Targeting the ERK1/2-Bax/Bcl-2 pathway may in part lead to sensitization of pancreatic cancer to gemcitabine.

Secreted clusterin gene silencing enhances chemosensitivity of a549 cells to cisplatin through AKT and ERK1/2 pathways in vitro.

BACKGROUND/AIMS: Several studies have shown secreted clusterin (sCLU) silencing directed against sCLU mRNA in sCLU-rich lung cancer cell lines sensitized cells to chemotherapy. However, the molecular mechanisms underlying the effect of sCLU silencing on lung cancer cell chemosensitivity is not known. In the present study, we aimed to determine that vector expressing short hairpin RNA against sCLU RNA (sCLU-shRNA) enhances the chemosensitivity in human small cell lung cancer A549 cells in vitro by inhibition of phosphorylated ERK1/2 (p-ERK1/2) and Akt (p-Akt). METHODS: The pCDNA3.1-sCLU and control scrambled pCDNA3.1 plasmid was constructed. We investigated the effects of sCLU overexpression by pCDNA3.1-sCLU transfection on chemosensitivity to cisplatin (DDP) in A549 cells in vitro. We down-regulated sCLU expression by short hairpin RNA against sCLU RNA (sCLU-shRNA) and investigated the effects on chemosensitivity to DDP in A549 cells and A549(DDP)in vitro. In order to confirm the correlation between sCLU and AKT and ERK1/2 signals, cells were treated with wortmannin and U0126. RESULTS: We found the chemotherapeutic agent DDP activated sCLU. Overexpression of sCLU increased cellular DDP chemoresistance in the A549(DDP) and pCDNA3. 1-sCLU transfected A549 cells via inhibition DDP-induced apoptosis. Whereas sCLU knockdown induced chemosensitization in the S549 and A549(DDP) cells via increase of DDP-induced apoptosis. sCLU overexpression activated pAKT Ser(473) and pERK1/2(Thr202/Tyr204), and vice versa. Inhibition of pAKT Ser(473) and pERK1/2(Thr202/Tyr204) was sufficient to induce significant recover y in chemosensitivity to DDP in A549(DDP) in the presence of sCLU overexpression. The DDP activated sCLU, which directly regulated pAKT and pERK1/2. CONCLUSIONS: This novel finding suggests that therapies directed against sCLU and its downstream signaling targets pAKT and pERK1/2 may have the potential to enhance the efficacy of DDP-based chemotherapy.

Targeting PEAK1 sensitizes anaplastic thyroid carcinoma cells harboring BRAFV600E to Vemurafenib by Bim upregulation.

Pseudopodium-enriched atypical kinase 1 (PEAK1) has been demonstrated to be upregulated in human malignancies and cells. Enhanced PEAK1 expression facilitates tumor cell survival and chemoresistance. However, the role of PEAK1 inhibition to anaplastic thyroid carcinoma cell (ATC) and vemurafenib resistance is still unknown. Here, we observed that targeting PEAK1 inhibited cell viability and colony formation, but not cell apoptosis in both of the 8505C and Hth74 cells in vitro. Targeting PEAK1 sensitized 8505C and Hth74 cells to vemurafenib by inducing cell apoptosis, and thereby decreasing cell viability. Mechanistically, vemurafenib treatment upregulated PEAK1 expression. Combined PEAK1 depletion and Vemurafenib treatment upregulated Bim expression. Targeting PEAK1 sensitized vemurafenib-induced apoptosis by upregulating Bim. In conclusion, vemurafenib resistance in ATC cells harboring BRAFV600E is associated with PEAK1 activation, resulting in the inhibition of pro-apoptotic Bim protein. Therefore, targeting PEAK1 may be an effective strategy to sensitize ATC harboring BRAFV600E to vemurafenib.

Immune cell signatures and inflammatory mediators: unraveling their genetic impact on chronic kidney disease through Mendelian randomization.

Prior research has established associations between immune cells, inflammatory proteins, and chronic kidney disease (CKD). Our Mendelian randomization study aims to elucidate the genetic causal relationships among these factors and CKD. We applied Mendelian randomization using genetic variants associated with CKD from a large genome-wide association study (GWAS) and inflammatory markers from a comprehensive GWAS summary. The causal links between exposures (immune cell subtypes and inflammatory proteins) and CKD were primarily analyzed using the inverse variance-weighted, supplemented by sensitivity analyses, including MR-Egger, weighted median, weighted mode, and MR-PRESSO. Our analysis identified both absolute and relative counts of CD28 + CD45RA + CD8 + T cell (OR = 1.01; 95% CI = 1.01-1.02; p < 0.001, FDR = 0.018) (OR = 1.01; 95% CI = 1.00-1.01; p < 0.001, FDR = 0.002), CD28 on CD39 + CD8 + T cell(OR = 0.97; 95% CI = 0.96-0.99; p < 0.001, FDR = 0.006), CD16 on CD14-CD16 + monocyte (OR = 1.02; 95% CI = 1.01-1.03; p < 0.001, FDR = 0.004) and cytokines, such as IL-17A(OR = 1.11, 95% CI = 1.06-1.16, p < 0.001, FDR = 0.001), and LIF-R(OR = 1.06, 95% CI = 1.02-1.10, p = 0.005, FDR = 0.043) that are genetically predisposed to influence the risk of CKD. Moreover, the study discovered that CKD itself may causatively lead to alterations in certain proteins, including CST5(OR = 1.16, 95% CI = 1.09-1.24, p < 0.001, FDR = 0.001). No evidence of reverse causality was found for any single biomarker and CKD. This comprehensive MR investigation supports a genetic causal nexus between certain immune cell subtypes, inflammatory proteins, and CKD. These findings enhance the understanding of CKD's immunological underpinnings and open avenues for targeted treatments.

Expression and Clinical Significance of Th1/Th2/Th17 Cytokines and Lymphocyte Subsets in PCNSL.

Purpose: Primary central nervous system lymphoma (PCNSL) responds favorably to radiation, chemotherapy and targeted drug therapy. However survival is usually worse, the treatment-related drug resistance and recurrence are still clinical problems to be solved urgently. Studies have shown that cytokines are expressed in varying degrees in patients with lymphoma, which is significantly related to the progression, poor prognosis and drug resistance of lymphoma. We explore the expression and clinical significance of Th1/Th2/Th17 cytokines and lymphocyte subsets in patients with PCNSL to provide a more sufficient theoretical basis for its diagnosis and treatment. Patients and Methods: We measured and analysed the levels of Th1/Th2/Th17 cytokines and the distribution of lymphocyte subsets (including Treg cells, CD3+, CD4+, CD8+, CD19+, and CD4+/CD8+) in 39 patients with PCNSL and 96 patients with diffuse large B-cell lymphoma (DLBCL) without central nervous system involvement. The cytokines of 13 healthy people and the lymphocyte subsets of 27 healthy people were measured as the control group. Results: We found a significant difference in the level of Th1/Th2/Th17 cytokines and lymphocyte subsets between PCNSL and healthy controls, especially IL-2, after treatment, which was significantly higher than before treatment (p<0.01). However, the level of CD19+ and CD4+/CD8+ decreased while CD8+ and CD3+ increased after treatment (regardless of whether the treatment was effective), and the difference was statistically significant. In addition, our analysis of different prognostic factors found that HD-MTX-based chemotherapy appears to have a longer progression-free survival and overall survival than osimertinib-based chemotherapy. Conclusion: There are significant differences in Th1/Th2/Th17 cytokines and lymphocyte subsets among PCNSL, DLBCL, and healthy controls, and their detection is helpful for the diagnosis, treatment, and prognosis of PCNSL. HD-MTX-based chemotherapy may still be the first choice for PCNSL.

Immunoglobulin G4-related lymph node disease with an orbital mass mimicking Castleman disease: A case report.

BACKGROUND: Immunoglobulin (Ig) G4-associated diseases are a group of systemic diseases involving multiple organs and are also known as IgG4-associated sclerosing diseases. IgG4-associated lymphadenopathy occurring in the lymph nodes is characterized by a lack of specificity due to its clinicopathological characteristics and must be differentiated from a variety of lesions, such as Castleman disease, lymphatic follicular reactive hyperplasia, and lymphoma. CASE SUMMARY: A 65-year-old male patient, with Guillain-Barre syndrome for 5 years, presented to our hospital complaining of bilateral orbital mass for 2 years. After hospitalization, the results of the patient's laboratory tests showed that immunoglobulin subgroup IgG4 was 33.90 g/L and IgG was 30.30 g/L, but serum interleukin-6 was normal. The pathological morphology of orbital mass and cervical lymph node were consistent, which showed that a large number of plasma cells and eosinophils were observed in the lymphatic follicles, and the interstitial fibrous tissue was proliferative. Immunohistochemistry showed that CD20 (B cells) (+), CD3 (T cells) (+), CD38 (+), IgG (+), IgG4 positive cells > 100/high powered field, and IgG4/IgG > 40%. Combined with clinical and immunohistochemical results, lymphadenopathy was consistent with Castleman disease-like IgG4-associated sclerosing disease. Prednisone acetate treatment was given at 40 mg/d. After 2 wk, the superficial lymph nodes and orbital masses shrank, and the IgG4 level decreased. As prednisone acetate was regularly used at a reduced dosage, no recurrence of the disease has been observed. CONCLUSION: This case suggested that it is necessary to proceed cautiously in clinical practice with such patients, and immunoglobulin, complement, interleukin-6, C-reactive protein, and other examinations should be performed to confirm the diagnosis.

Correlation of NUF2 Overexpression with Poorer Patient Survival in Multiple Cancers.

PURPOSE: NUF2 has been implicated in multiple cancers recently, suggesting NUF2 may play a role in the common tumorigenesis process. In this study, we aim to perform comprehensive meta-analysis of NUF2 expression in the cancer types included in the Cancer Genome Atlas (TCGA). MATERIALS AND METHODS: RNA-sequencing data in 31 cancer types in the TCGA data and 11 independent datasets were used to examine NUF2 expression. Silencing NUF2 using targeting shRNAs in hepatocellular carcinoma (HCC) cell lines was used to evaluate NUF2's role in HCC in vitro and in vivo. RESULTS: NUF2 up-regulation is significantly observed in 23 out of the 31 cancer types in the TCGA datasets and validated in 13 major cancer types using 11 independent datasets. NUF2 overexpression was clinically important as high NUF2 was significantly associated with tumor stages in eight different cancers. High NUF2 was also associated with significantly poorer patient overall survival and disease-free survival in eight and six cancers, respectively. We proceeded to validate NUF2 overexpression and its negative association with overall survival at the protein level in an independent cohort of 40 HCC patients. Compared to the non-targeting controls, NUF2 knockdown cells showed significantly reduced ability to grow, migrate into a scratch wound and invade the 8 µm porous membrane in vitro. Moreover, NUF2 knockdown cells also formed significantly smaller tumors than control cells in mouse xenograft assays in vivo. CONCLUSION: NUF2 up-regulation is a common feature of many cancers. The prognostic potential and functional impact of NUF2 up-regulation warrant further studies.

miR-211 alleviates ischaemia/reperfusion-induced kidney injury by targeting TGFßR2/TGF-ß/SMAD3 pathway.

MicroRNA-211 (miR-211) is closely related to apoptosis and plays an important role in ischemia/reperfusion (I/R) injury. Whether miR-211 is involved in the protective effects in renal I/R injury is unknown. In this study, we evaluated the role of miR-211 in human tubular epithelial cells in response to hypoxia-reoxygenation (H/R) stimulation and I/R injury in vitro and in vivo. The results revealed that miR-211 was down-regulated and TGFßR2 was up-regulated in human kidney (HK-2) cells subjected to H/R. Luciferase reporter assay showed that TGFßR2 was a direct target of miR-211. Enforced miR-211 expression decreased H/R-induced HK-2 cell apoptosis and increased cell viability, and targeting miR-211 further increased H/R-induced HK-2 cell apoptosis and decreased cell viability. However, the effect of miR-211 was reversed by targeting TGFßR2 or enforced TGFßR2 expression in miR-211 overexpressing cells or miR-211 downexpressing cells. Moreover, we confirmed that miR-211 interacted with TGFßR2, and regulating TGF-ß/SMAD3 signal. In vivo in mice, miR-211 overexpression ameliorates biochemical and histological kidney injury, reduces apoptosis in mice following I/R. On the contrary, miR-211 downexpressing promoted histological kidney injury and increased apoptosis in mice following I/R. Inhibition of miR-211 or miR-211 overexpression inhibited TGF-ß/SMAD3 pathways or activated TGF-ß/SMAD3 signal pathways in vitro and in vivo, which are critical for cell survival. Our findings suggested that miR-211 suppress apoptosis and relieve kidney injury following H/R or I/R via targeting TGFßR2/TGF-ß/SMAD3 signals. Therefore, miR-211 may be as therapeutic potential for I/R- induced kidney injury.

Clinical significance of eukaryotic translation initiation factor 5A2 in papillary thyroid cancer.

Eukaryotic translation initiation factor 5A2 (eIF5A2) plays an important role in tumor progression and prognosis evaluation. However, the potential role of eIF5A2 in human papillary thyroid cancer (PTC) is unknown. In this study, we aim to investigate the association between eIF5A2 expression and PTC clinical outcomes and underlying its Biological function in PTC cells in vitro and in vivo. The expression of eIF5A2 was examined by immunohistochemistry in PTC tissues and its adjacent tissue (n = 39) from 207 PTC patients. Functional analysis of eIF5A2 was performed in PTC cell lines in vitro and in vivo. The results showed that eIF5A2 was overexpressed in PTC tissues compared with the adjacent tissues. Enhanced eIF5A2 expression was significantly correlated with extrathyroidal extension (p = 0.012), lymph node metastasis (p = 0.002), TNM stage (p = 0.006), T classification (p = 0.047) and BRAF V600E mutation (p = 0.036). EIF5A2 inhibition prevented PTC cell growth, invasiveness and migration and induced cell apoptosis in vitro. Furthermore, eIF5A2 depletion inhibited tumor growth and metastasis in vivo. The data indicated that eIF5A2 could be employed as a novel prognostic marker and effective therapeutic target for PTC.

Sebaceous lymphadenocarcinoma of the parotid gland: A case report.

BACKGROUND: Sebaceous lymphadenoma is a benign tumor that occurs rarely in the salivary glands, most commonly in the parotid glands or periparotid lymph nodes, and even more rarely undergoes malignant transformation into a sebaceous lymphadenocarcinoma. CASE SUMMARY: We report an 82-year-old woman who presented with a painless mass in the right parotid region. We performed extended surgical resection of the parotid gland mass. Intraoperative pathology revealed a sebaceous lymphadenocarcinoma with metastasis into the periparotid cervical lymph nodes, so we also performed neck dissection and lymph node resection. Postoperative pathology confirmed the diagnosis. The literature review revealed that this was the seventh reported case of sebaceous lymphadenocarcinoma and the second reported case of cervical lymph node metastasis and infiltration of the skin of the parotid gland. CONCLUSION: Treatment of sebaceous lymphadenocarcinoma depends on the typing and clinical staging of the cancer. Extensive resection is the first choice, and adjuvant radiotherapy should be given to patients with high-grade tumors or those at an advanced clinical stage.

miR-25-3p inhibition impairs tumorigenesis and invasion in gastric cancer cells in vitro and in vivo.

Deregulated expression of microRNAs (miRNAs) plays a role in the pathogenesis and progression of gastric cancer (GC). Among upregulated miRNAs, miR-25-3p has oncogenic potential and therefore represents an attractive target for the treatment of GC. Here, we investigated the role of miR-25-3p on GC cells in vitro and in vivo. We found that miR-25-3p overexpression significantly promoted growth and invasion of gastric cancer cells in vitro. Conversely, targeting miR-25-3p triggered significant inhibition of growth, invasion and migration in GC cells in vitro. In vivo delivery of miR-25-3p inhibitors induced significant anti-tumor activity in SCID mice bearing human GC xenografts. Our findings showed the evidence that in vivo antagonism of miR-25-3p impaired tumorigenesis, providing the rationale for clinical development of miR-25-3p inhibitors in GC.