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In modern grid systems, electrical fires caused by faulty arcs occur more frequently. Arc protective clothing is the equipment that can effectively protect personal safety. Among them, polyimide insulation materials have the advantages of high-temperature resistance and high thermal resistance. Their performance in the field of arc protection is of high research value. In this paper, the effect of faulty arc on polyimide insulation material is studied by experimental and simulation control modes. The COMSOL software is used to simulate the process of electric arc affecting polyimide insulation material, and to simulate the physical field distribution of electric arc with different electrode spacing and different arc currents. An arc generation device is built, a copper calorimeter is designed to record the temperature rise of each experiment, a variety of arc parameters is changed, and the performance of polyimide insulation materials is analyzed to block the fault arc. A fault arc experimental platform was built, using a copper calorimeter to record the temperature rise of each experiment. Varying multiple arc parameters to analyze the performance of polyimide insulation materials in blocking fault arcs. The simulation and test results show that polyimide has an obvious barrier effect on the radiation temperature of the fault arc, and it can show good thermal insulation under different arc conditions, which proves that polyimide insulation materials have excellent protection performance against fault arcs in the energized operation environment.

Acute promyelocytic leukemia (APL) is characterized by the presence of promyelocytic leukemia-retinoic acid receptor α (PML-RARα) fusion gene, which is formed following the specific chromosomal translocation t(15;17)(q22;q21). However, cases with PML-RARα generated by occult t(15;17) which are negative by both cytogenetics and fluorescence in situ hybridization (FISH), are difficult to diagnose, leading to impaired treatment effectiveness. In the present study, we reported a case of a 66-year-old male patient, and bone marrow morphology, flow cytometry and cytogenetics did not support the diagnosis of APL. Molecular techniques, such as reverse-transcription polymerase chain reaction (RT-PCR), showed the existence of a cryptic PML-RARα fusion gene, and sequence analysis revealed a new variable isoform. Hotspot gene mutation analysis showed a biallelic CEBPA mutation. He received IA chemotherapy and all-trans retinoic acid (ATRA) treatment, and finally achieved complete remission. This case report provided valuable insights into the relevance of the correct identification of atypical PML–RARα fusion gene and biallelic CEBPA mutation. Moreover, combination of IA chemotherapy and ATRA treatment suggested a good clinical effect in this atypical PML–RARα.

There are no standard therapies for patients with relapse/refractory diffuse large B-cell lymphoma (R/R DLBCL) who are ineligible for transplantation. Recently, polatuzumab vedotin (pola) combined with rituximab and bendamustine (pola-BR) has been validated in clinical trials. However, pola is not approved in China and clinical data in Chinese population is still lacking. This study is intended to preliminarily evaluate the clinical effectiveness of this regimen in China.This study retrospectively evaluated the efficacy and tolerability of pola-BR regimen in Chinese R/R DLBCL patients treated in a compassionate use program (CUP; pola CUP) after failing ≥2 prior regimens. Patients participated in CUP at 4 Chinese centers from December 2019 to July 2020 were enrolled. The outcomes were the overall response rate (ORR), complete response (CR) rate, and progression-free survival (PFS). Adverse events (AEs) were collected.A total of 28 patients enrolled in the pola CUP were included. At data analysis cut-off (30 September 2020), the best overall response (BOR) rate was 71.4%, and a CR rate of 25.0% was obtained. The estimated median PFS of all patients was 200 [95% confidence interval (CI): 97 to not evaluable (NE)] days. The most common AEs were thrombocytopenia (32.1%), neutropenia (28.6%), and fever (14.3%). High-grade (grade ≥2) peripheral neuropathy (PN) was not observed.These preliminary data suggested that the pola-BR regimen has promising efficacy and tolerable safety in Chinese transplantation ineligible R/R DLBCL patients. Hence, pola-BR may be an optional regimen. Considering the limited sample size and short follow-up, larger sample and long-term survival outcome studies are warranted.

Background Interleukin-10 (IL-10) is an independent factor for predicting adverse outcomes in pediatric patients with hemophagocytic lymphohistiocytosis (HLH). However, little is known about its prognostic value in adult patients. Methods This single center retrospective study was conducted to explore the prognostic value of IL-10 in 101 adults newly diagnosed with HLH. The serum interleukin levels were quantitatively determined by chemiluminescence using cytokine profiling kits. Results Serum IL-10 levels were significantly increased in adult HLH patients. Elevated IL-10 levels was correlated with lower concentrations of hemoglobin (r = − 0.279, P = 0.005). IL-10 levels were significantly lower in patients with macrophage activation syndrome (MAS) than in those with infection-associated HLH (IAHS) and malignancy-associated HLH (MAHS) (P = 0.033, P = 0.012). Patients with MAS had relatively longer survival than those with IAHS and MAHS (P 9/L, lactate dehydrogenase ≥ 700 IU/L, albumin 1050 µg/L and IL-10 ≥ 129 pg/mL were poor prognostic factors for survival. However, multivariate analysis revealed that only high serum IL-10 levels (≥ 129 pg/mL) at diagnosis and high post-treatment ferritin levels (> 1050 µg/L) were independent risk factors for poor overall survival in adult HLH patients (HR: 4.087, 95% CI 2.064–8.090, P P Conclusions Our results suggest that higher serum IL-10 levels might be a prognostic marker in adult HLH patients.

High-risk HPV is clearly associated with cervical cancer. HPV integration has been confirmed to promote carcinogenesis in the previous studies. In our study, a total of 285 DNA breakpoints and 287 RNA breakpoints were collected. We analyzed the characteristic of HPV integration in the DNA and RNA samples. The results revealed that the patterns of HPV integration in RNA and DNA samples differ significantly. FHIT, KLF5, and LINC00392 were the hotspot genes integrated by HPV in the DNA samples. RAD51B, CASC8, CASC21, ERBB2, TP63, TEX41, RAP2B, and MYC were the hotspot genes integrated by HPV in RNA samples. Breakpoints of DNA samples were significantly prone to the region of INTRON (P < 0.01, Chi-squared test), whereas in the RNA samples, the breakpoints were prone to EXON. Pathway analysis had revealed that the breakpoints of RNA samples were enriched in the pathways of transcriptional misregulation in cancer, cancer pathway, and pathway of adherens junction. Breakpoints of DNA samples were enriched in the pathway of cholinergic synapse. In summary, our data helped to gain insights into the HPV integration sites in DNA and RNA samples of cervical cancer. It had provided theoretical basis for understanding the mechanism of tumorigenesis from the perspective of HPV integration in the HPV-associated cervical cancers.

Background For patients with relapse/refractory(R/R) Diffuse Large B Cell Lymphoma (DLBCL), intensive therapy (such as R-ICE, R-DHAP) followed by autologous stem cell transplant (ASCT) can provide potential cure. However, not all patients would be eligible for such aggressive therapy. The ASCT ineligible or patients have very low survival rates and no curative options. Polatuzumab vedotin (Pola) is a conjugated antibody that delivers the microtubule inhibitor MMAE to CD79b-expressing cells. Pola administered in combination with Bendamustine-Rituximab (P-BR) has been approved for R/R DLBCL patients in USA and Europe consecutively. But real-life data of Pola on efficacy and safety in this setting especially in Chinese patients remain very limited. Aim This study aims to investigate the efficacy and tolerability of Pola with BR or R in R/R patients with DLBCL treated through a Compassionate Use Program (CUP) after failing ≥2 prior regimens. Methods We collected and analyzed the data of all patients enrolled in Pola CUP in four Chinese centers. Patients with R/R DLBCL who have exhausted all therapeutic options after at least 2 prior treatments could be enrolled in this program. Pola was administered at a dose of 1.8 mg/kg/cycle iv in combination with rituximab±bendamustine for a total of up to 6 cycles. Response was assessed after every 2 cycles and at end of treatment. Results From Dec 12 2019 to Jul 30 2020, 27 patients were treated in the CUP of Pola and there are 20 patients whose diseases had already been assessed at least once for the response evaluation. Baseline characteristics of the 20 patients are shown in Table1. Nine patients received Pola-BR combination and 3 of them received the bendamustine combined regimen after the 3rd or 4th cycle in order to improve the efficacy. For the other 11 patients only Pola-R was administered. All patients received rituximab in front lines and 80.0%(16/20) of them are refractory to the prior therapy (no response or relapsed≤6 mon). 70.0% (14/20) patients had a high-intermediate or high risk disease (IPI score≥3); 10.0% (2/20) had ECOG performance status (PS) 3-4. 25.0% (5/20) patients had already received prior Car-T and 5.0% (1/20) had prior ASCT therapy. At time of analysis, six patients finished all 6 cycles of treatment and 3 discontinued therapy due to personal reason or disease progression. The remaining patients are still in the process of treatment. The achieved overall response was Complete Response (CR) in 1 patients (5.0%) and Partial Response (PR) in 15 patients (75.0%). One patient progressed after 2 cycles of Pola-R therapy, but achieved PR after receiving Bendamustine combined therapy from the 3rd cycle. The overall response rate and treatment duration is shown in table 2 and Figure 1. The median follow-up is 48 days and the progression free survival (PFS) of the two progressed patients is 29 and 148 days. (Table 3 & Figure 2). The main toxicity was hematological. Four patients developed grade 3-4 neutropenia (20.0%) and 2 patient (10.0%) had grade 3-4 thrombocytopenia. Febrile neutropenia was reported in 2 patients. One patient had pneumonia but recovered after anti-infection therapy. The adverse event of peripheral neuropathy was not observed. Conclusion For this R/R DLBCL cohort with heavily treated, high risk and refractory diseases, the Pola-(B)R regimen still achieved promising efficacy. However considering the limited sample size and short follow-up, more mature data and long-term survival outcomes is warrant. Key words Relapse/refractory; DLBCL; Polatuzumab Vedotin; Compassionate Use Disclosures No relevant conflicts of interest to declare.

Background The current study aimed to evaluate the expression of circular RNA (circRNA) CDR1as in bladder urothelial carcinoma and adjacent normal tissues, thereby laying the foundation for the research of bladder urothelial carcinoma. Methods The level of CDR1as was evaluated in the tissues of bladder urothelial carcinoma patients. ROC analysis was carried out to explore the possible diagnostic value of CDR1as. Results In the current study, we showed novel data that the expression of CDR1as in bladder urothelial carcinoma tissues was significantly higher than that in adjacent tissues. Furthermore, the expression of CDR1as was significantly higher in non-muscle invasive bladder cancer (NMIBC) and high-grade cancer tissues than in muscle invasive bladder cancer (MIBC) and low-grade cancer tissues. In patients with lymph node metastasis, the expres-sion of CDR1as was also significantly higher. Moreover, the expression of CDR1as was higher in high-stage, high-grade bladder urothelial carcinoma than in low-stage and low-grade cancer tissues. Real time PCR analysis showed that there was no difference in the expression of CDR1as among the patients according to the grouping of gender (male vs. female), age (≤ 65 years vs. > 65 years), tumor size (≤ 3 cm vs. > 3 cm), and lymphatic invasion (LVI). Conclusions The current study for the first time showed upregulation of CDR1as may be involved in the development and progression of bladder urothelial carcinoma.

Background: Circular RNAs (circRNAs) play an important role in many neurological diseases and can serve as biomarkers for these diseases. However, the information about circRNAs in Parkinson disease (PD) remained limited. In this study, we aimed to determine the circRNAs expression profile in PD patients and discuss the significance of circRNAs in the diagnosis of PD. Methods and Results: Using RNA-sequencing in peripheral blood RNAs, we showed that a significant number of mRNAs or circRNAs were differentially expressed between PD patients and normal controls (NCs), which included 273 up-regulated and 493 down-regulated mRNAs, and 129 up-regulated and 282 down-regulated circRNAs, respectively. Functional analysis was performed using the Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis, and the results showed that the second most enriched KEGG pathway was PD. These data suggest that the levels of mRNAs and circRNAs in peripheral blood could be potentially used as biomarkers for PD. In addition, we correlated mRNAs and circRNAs by constructing a competing endogenous RNA (ceRNA) network in PD. The resulted-in ceRNA network included 10 differentially expressed mRNAs from PD pathway, 13 predicted miRNAs, and 10 differentially expressed circRNAs. Conclusion: Collectively, we first characterized the expression profiles of circRNAs and mRNAs in peripheral blood from PD patients and proposed their possible characters in the pathogenesis of PD. These results provided valuable insights into the clues underlying the pathogenesis of PD.

Background: As a hallmark driver of multiple myeloma (MM), MM bone disease (MBD) is unique in that it is characterized by severely impaired osteoblast activity resulting from blocked osteogenesis in bone marrow-derived mesenchymal stem cells (BM-MSCs). The mechanisms underlying this preferential blockade are incompletely understood. Methods: miRNA expression of MM cell-derived extracellular vesicles (MM-EVs) was detected by RNA sequencing. MM-EVs impaired osteogenesis and exacerbated MBD were in vitro and in vivo validated by histochemical staining, qPCR and micro-CT. We additionally examined the correlation between CD138+ circulating EVs (cirEVs) count and bone lesion in de novo MM patients. Results: Here, by sequencing and bioinformatics analysis, we found that MM-EVs were enriched in various molecules negatively regulating osteogenesis. We experimentally verified that MM-EVs inhibited BM-MSC osteogenesis, induced elevated expression of miR-103a-3p inhibiting osteogenesis in BM-MSCs, and increased cell viability and interleukin-6 secretion in MM cells. In a mouse model, MM-EVs that were injected into the marrow space of the left tibia led to impaired osteogenesis and exacerbated MBD and MM progression. Furthermore, the levels of CD138+ cirEVs in the peripheral blood were positively correlated with the number of MM bone lesions in MM patients. Conclusions: These findings suggest that MM-EVs play a pivotal role in the development of severely impaired osteoblast activity, which represents a novel biomarker for the precise diagnosis of MBD and a compelling rationale for exploring MM-EVs as a therapeutic target.

Renal impairment (RI) is one of the hallmarks of multiple myeloma (MM) and carries a poor prognosis. Microvesicles (MVs) are membrane vesicles and play an important role in disease progression. Here, we investigated the role of MVs derived from MM cells (MM-MVs) in RI of MM. We found that MM-MVs significantly inhibited viability and induced apoptosis, but not epithelial-mesenchymal transition in human kidney-2 (HK-2), a human renal tubular epithelial cell line. The protein levels of cleaved caspase-3, 8, and 9, and E-cadherin, were increased, but vementin levels were decreased in the HK-2 cells treated with MM-MVs. Through a comparative sequencing and analysis of RNA content between the MVs from RPMI8226 MM cells (RPMI8226-MVs) and K562 leukemia cells, RPMI8226-MVs were enriched with more renal-pathogenic miRNAs, in which the selective miRNAs may participate in the up-regulation of the levels of cleaved caspase-3. Furthermore, the levels of CD138+ circulating MVs (cirMVs) in the peripheral blood were positively correlated with the severity of RI in newly-diagnosed MM. Our study supports MM-MVs representing a previously undescribed factor and playing a potential role in the development of RI of MM patients, and sheds light on the potential application of CD138+ cirMV counts in precise diagnosis of RI in MM and exploring MM-MVs as a therapeutic target.

Microvesicles (MVs) in body fluids participate in a variety of physical and pathological processes, and are regarded as potential biomarkers for numerous diseases. Flow cytometry (FCM) is among the most frequently used techniques for MV detection. However, different handling methods unavoidably cause pre-analytical variations in the counts and sizes of MVs determined by FCM. The aim of the present study was to investigate the effect of centrifugation, storage conditions and anticoagulant on MV measurements. Blood samples were obtained from 13 healthy donors, including 4 women and 9 men. Calcein-AM staining was used to label MVs and assess the impact of pre-analytical preparation, including centrifugation, and storage conditions on MV measurements obtained using FCM. The range of factors investigated for comparison included: Platelet-free plasma (PFP) stored at -80°C for 1 or 4 weeks; MVs stored at 4°C for 3-4 days or 1 week; MVs frozen at -80°C for 1 or 4 weeks; and anticoagulants, either heparin or ethylenediaminetetraacetic acid (EDTA). No statistically significant differences in MV counts were detected between the two centrifugation speeds (16,000 and 20,500 × g) or among the three centrifugation times (15, 30 and 60 min) investigated. Similarly, no significant differences were noted in MV counts between the two anticoagulants tested (heparin and EDTA). However, the storage of PFP or MVs in heparin-anticoagulated plasma for different periods markedly affected the detected MV counts and size distribution. The counts and sizes of MVs from EDTA-anticoagulated plasma were only affected when the MVs were frozen at -80°C for 4 weeks. In conclusion, calcein-AM is able to efficiently identify MVs from plasma and may be an alternative to Annexin V for MV staining. EDTA preserves the MV counts and size more accurately compared with heparin under calcein-AM staining. PFP centrifuged at 16,000 × g for 15 min is sufficient to isolate MVs, which enables the batch processing of samples. PFP, rather than MVs alone, appears to be the preferable mode of sample storage, as MVs stored in PFP were less affected by storage temperature and duration. The present study provides a methodology for MV collection, storage and isolation, to facilitate further investigation of MVs as biomarkers in disease.

This study examined the mechanism of the inhibitory effect of parthenolide (PTL) on the activity of NF-κB in multiple myeloma (MM). Human multiple myeloma cell line RPMI 8226 cells were treated with or without different concentrations of PTL for various time periods, and then MTT assay was used to detect cell proliferation. Cell cycle and apoptosis were flow cytometrically detected. The level of protein ubiquitination was determined by using immunoprecipitation. Western blotting was employed to measure the level of total protein ubiquitination, the expression of IκB-α in cell plasma and the content of p65 in nucleus. The content of p65 in nucleus before and after PTL treatment was also examined with immunofluorescence. Exposure of RPMI 8226 cells to PTL attenuated the level of ubiquitinated Nemo, increased the expression of IκB-α and reduced the level of p65 in nucleus, finally leading to the decrease of the activity of NF-κB. PTL inhibited cell proliferation, induced apoptosis and blocked cell cycle. Furthermore, the levels of ubiquitinated tumor necrosis factor receptor-associated factor 6 (TRAF6) and total proteins were decreased after PTL treatment. By using Autodock software package, we predicted that PTL could bind to TRAF6 directly and tightly. Taken together, our findings suggest that PTL inhibits the activation of NF-κB signaling pathway via directly binding with TRAF6, thereby suppressing MM cell proliferation and inducing apoptosis.

Multiple myeloma (MM) is a plasma cell malignancy characterized by a high capacity to induce osteolytic bone lesions. MM patients with osteolytic bone lesions have lower numbers of osteoblasts and decreased bone formation, which plays a critical role in the bone-destructive process. Although the mechanism of estrogen action on bone cells and myeloma cells has been widely investigated, estrogen action on bone cells in MM is unknown. In this study, the effects of the gonadal hormone 17beta-estradiol on cell growth, alkaline phosphatase (ALP) activity, mineralization capacity, and RANKL/OPG ratios in primary rat osteoblasts cultured with MM cell conditioned medium (CM) or co-cultured with RPMI8226 cells were investigated. Treatments of 10(-2) to 10 nM 17beta-estradiol reversed inhibition of proliferation and ALP activity of osteoblasts by myeloma cells in a dose-dependent manner, and 10(-2) to 1 nM 17beta-estradiol reversed inhibition of the mineralization capacity of osteoblasts by myeloma cells. In co-culture experiments with primary rat osteoblasts and myeloma cells, treatments of 10(-2) to 10 nM 17beta-estradiol down-regulated transcription and secretion of RANKL and up-regulated transcription and secretion of OPG in the osteoblasts, reversing the effects of co-cultured myeloma cells. These findings suggest that 17beta-estradiol may temper the inhibitory effects of myeloma cells on osteoblasts and improve RANKL/OPG balance, providing a new agent for treatment of bone disease in myeloma.

The inhibitory effects of parthenolide (PTL) on angiogenesis induced by multiple myeloma (MM) cells in vitro and the mechanism were investigated. Human MM line RPMI8226 cells were cultured in vitro. The effects of MM culture supernatant on the migration and tubule formation ability of human umbilical vein endothelial cells (HUVECs) treated with PTL were observed. By using Western blot, the expression of p65 and IkappaB-alpha in MM cells was detected. RT-PCR was used to assay the expression of VEGF, IL-6, MMP2 and MMP9 mRNA in MM cells. ELISA was used to measure the levels of VEGF and IL-6 in MM cell culture supernatant. The expression of MMP2 and MMP9 in MM cells was examined by immunohistochemistry. (1) In 3.5, 5.0, 7.5 and 10 micromol/L PTL groups the number of migrated cells was 310 +/- 56, 207 +/- 28, 127 +/- 21 and 49 +/- 10 respectively, which was significantly different from that in positive control group (598 +/- 47) (P0.01). In 3.5 and 5.0 micromol/L PTL groups the areas of capillary-like structures were 0.092 +/- 0.003 and 0.063 +/- 0.002 mm2, significantly less than in positive control group (0.262 +/- 0.012 mm2) (P0.01), but in 7.5 and 10 micromol/L PTL groups no capillary-like structures were found; (2) After treatment with different concentrations of PTL for 48 h, the expression of p65 protein was gradually decreased, while that of IkappaB-alpha was gradually enhanced with the increased concentration of PTL; (3) After treatment with 3.5, 5.0, 7.5 and 10 micromol/L PTL for 48 h, the VEGF levels in the supernatant were 2373.4 +/- 392.2, 1982.3 +/- 293.3, 1247.0 +/- 338.4 and 936.5+/-168.5 pg/mL respectively, significantly different from those in positive control group (2729 +/- 440.0 pg/mL) (P0.05). After treatment with 7.5 and 10 micromol/L PTL, the IL-6 levels in the culture supernatant were 59.6 +/- 2.8 and 41.4 +/- 9.8 pg/mL respectively, significantly lower than in positive control group (1287.3 +/- 43.5 pg/mL) (P0.05); (4) RT-PCR revealed that PTL could significantly inhibit the expression of VEGF and IL-6 mRNA in MM cells, but not influence the expression of MMP2 and MMP9 mRNA.; (5) Immunohistochemistry indicated that PTL had no significant effects on the expression of MMP2 and MMP9 protein in MM cells. It was concluded that the abilities of the culture supernatant of MM cells treated with PTL to induce endothelial cells migration and tubule formation were significantly reduced, suggesting PTL could obviously inhibit the angiogenesis induced by MM cells. PTL could decrease NF-kappaB activity and significantly suppress the expression of VEGF and IL-6 mRNA and protein, which might contribute to the mechanism by which PTL inhibited the angiogenesis induced by MM cells.