Transarterial Chemoembolization (TACE) Combined with Lenvatinib versus TACE Alone in Intermediate-Stage Hepatocellular Carcinoma Patients Beyond Up-To-Seven Criteria: A Retrospective, Propensity Score-Matched Analysis.

RATIONALE AND OBJECTIVES: To compare the treatment efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib versus TACE alone in patients with intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-seven criteria. MATERIALS AND METHODS: A total of 107 newly diagnosed HCC patients with Barcelona Clinic Liver Cancer stage B HCC beyond up-to-seven criteria were included in this retrospective cohort study. These patients were divided into two groups: TACE-Lenv group and TACE alone group. Propensity score matching was used to account for potential confounding factors. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), downstaging rate, liver function, and adverse events (AEs) were recorded and evaluated. RESULTS: Both the median OS and median PFS were significantly longer in the TACE-Lenv group compared to the TACE alone group (median OS: 28.0 vs 12.0 months, P = 0.017; median PFS [mRECIST]: 8.2 vs 3.7 months, P = 0.018; median PFS [RECIST v1.1]: 8.9 vs 3.7 months, P = 0.003). Furthermore, the ORR and DCR were also significantly higher in TACE-Lenv group (ORR: 94% [30/32] vs 47% [15/32], P < 0.001; DCR: 97% [31/32] vs 62% [20/32], P < 0.001). There were no significant differences in terms of liver function and grade 3 or 4 AEs rate between two groups. CONCLUSION: The combination of TACE and lenvatinib provides clinical benefits for patients with intermediate HCC beyond the up-to-seven criteria, has an acceptable safety profile, shows a trend towards improving liver function, and does not increase the occurrence of grade 3-4 AEs. KEY POINTS: The efficacy of transarterial chemoembolization in intermediate-stage hepatocellular carcinoma patients is partially unsatisfactory. Addition of lenvatinib to transarterial chemoembolization improves OS, PFS, ORR, and DCR for patients with intermediate-stage hepatocellular carcinoma beyond the up-to-seven criteria. This combination therapy is a superior treatment option for intermediate-stage hepatocellular carcinoma patients with high tumor burden.

Causal Effects of COVID-19 on the Risk of Thrombosis: A Two-Sample Mendel Randomization Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) and thrombosis are linked, but the biomolecular mechanism is unclear. We aimed to investigate the causal relationship between COVID-19 and thrombotic biomarkers. METHODS: We used two-sample Mendelian randomization (MR) to assess the effect of COVID-19 on 20 thrombotic biomarkers. We estimated causality using inverse variance weighting with multiplicative random effect, and performed sensitivity analysis using weighted median, MR-Egger regression and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) methods. All the results were examined by false discovery rate (FDR) with the Benjamin and Hochberg method for this correction to minimize false positives. We used R language for the analysis. RESULTS: All COVID-19 classes showed lower levels of tissue factor pathway inhibitor (TFPI) and interleukin-1 receptor type 1 (IL-1R1). COVID-19 significantly reduced TFPI (odds ratio [OR] = 0.639, 95% confidence interval [CI]: 0.435-0.938) and IL-1R1 (OR = 0.603, 95% CI = 0.417-0.872), nearly doubling the odds. We also found that COVID-19 lowered multiple coagulation factor deficiency protein 2 and increased C-C motif chemokine 3. Hospitalized COVID-19 cases had less plasminogen activator, tissue type (tPA) and P-selectin glycoprotein ligand 1 (PSGL-1), while severe cases had higher mean platelet volume (MPV) and lower platelet count. These changes in TFPI, tPA, IL-1R1, MPV, and platelet count suggested a higher risk of thrombosis. Decreased PSGL-1 indicated a lower risk of thrombosis. CONCLUSION: TFPI, IL-1R, and seven other indicators provide causal clues of the pathogenesis of COVID-19 and thrombosis. This study demonstrated that COVID-19 causally influences thrombosis at the biomolecular level.

Development and validation of a prognostic nomogram for patients with laryngeal cancer with synchronous or metachronous lung cancer.

BACKGROUND: The objective of this study was to examine the independent prognostic factors of laryngeal cancer with synchronous or metachronous lung cancer (LCSMLC), and to generate and verify a clinical prediction model. METHODS: In this study, laryngeal cancer alone and LCSMLC were defined using the Surveillance, Epidemiology, and End Results (SEER) database. Risk factors of patients with LCSMLC were analyzed through univariate and multivariate logistic regression analysis. Independent prognostic factors were selected by Cox regression analyses, on the basis of which a nomogram was constructed using R code. Kaplan-Meier survival analyses were applied to test the application of a risk stratification system. Finally, we conducted a comparison of the American Joint Committee on Cancer (AJCC) staging system of laryngeal cancer with the new model of nomogram and risk stratification. For further validation of the nomogram, data from patients at two Chinese independent institutions were also analyzed. RESULTS: According to the eligibility criteria, 32 429 patients with laryngeal cancer alone and 641 patients with LCSMLC from the SEER database (the training cohort) and additional 61 patients from two Chinese independent institutions (the external validation cohort) were included for final analyses. Compared with patients with laryngeal cancer who did not have synchronous or metachronous lung cancer, age, sex, race, primary site of laryngeal cancer, grade, and stage were risk factors for LCSMLC, while marriage, surgery, radiation therapy, and chemotherapy are not their risk factors. Age, two cancers' interval, pathological type, stage, surgery, radiation, primary lung site, and primary throat site were independent prognostic predictors of LCSMLC. The risk stratification system of high-, medium-, and low-risk groups significantly distinguished the prognosis in different patients with LCSMLC, regardless of the training cohort or the validation cohort. Compared with the 6th AJCC TNM stage of laryngeal cancer, the new model of nomogram and risk stratification showed an improved net benefit. CONCLUSIONS: Age, sex, race, primary site of laryngeal cancer, grade, and stage were risk factors for LCSMLC. An individualized clinical prognostic predictive model by nomogram was generated and validated, which showed superior prediction ability for LCSMLC.

An EMC-Hpo-Yki axis maintains intestinal homeostasis under physiological and pathological conditions.

Balanced control of stem cell proliferation and differentiation underlines tissue homeostasis. Disruption of tissue homeostasis often results in many diseases. However, how endogenous factors influence the proliferation and differentiation of intestinal stem cells (ISCs) under physiological and pathological conditions remains poorly understood. Here, we find that the evolutionarily conserved endoplasmic reticulum membrane protein complex (EMC) negatively regulates ISC proliferation and intestinal homeostasis. Compromising EMC function in progenitors leads to excessive ISC proliferation and intestinal homeostasis disruption. Mechanistically, the EMC associates with and stabilizes Hippo (Hpo) protein, the key component of the Hpo signaling pathway. In the absence of EMC, Yorkie (Yki) is activated to promote ISC proliferation due to Hpo destruction. The EMC-Hpo-Yki axis also functions in enterocytes to maintain intestinal homeostasis. Importantly, the levels of the EMC are dramatically diminished in tunicamycin-treated animals, leading to Hpo destruction, thereby resulting in intestinal homeostasis disruption due to Yki activation. Thus, our study uncovers the molecular mechanism underlying the action of the EMC in intestinal homeostasis maintenance under physiological and pathological conditions and provides new insight into the pathogenesis of tunicamycin-induced tumorigenesis.

Diamond controls epithelial polarity through the dynactin-dynein complex.

Epithelial polarity is critical for proper functions of epithelial tissues, tumorigenesis, and metastasis. The evolutionarily conserved transmembrane protein Crumbs (Crb) is a key regulator of epithelial polarity. Both Crb protein and its transcripts are apically localized in epithelial cells. However, it remains not fully understood how they are targeted to the apical domain. Here, using Drosophila ovarian follicular epithelia as a model, we show that epithelial polarity is lost and Crb protein is absent in the apical domain in follicular cells (FCs) in the absence of Diamond (Dind). Interestingly, Dind is found to associate with different components of the dynactin-dynein complex through co-IP-MS analysis. Dind stabilizes dynactin and depletion of dynactin results in almost identical defects as those observed in dind-defective FCs. Finally, both Dind and dynactin are also required for the apical localization of crb transcripts in FCs. Thus our data illustrate that Dind functions through dynactin/dynein-mediated transport of both Crb protein and its transcripts to the apical domain to control epithelial apico-basal (A/B) polarity.

Low-disturbance automatic bias point control for optical IQ modulator using digital chaotic waveform as dither signals.

A low-disturbance automatic bias point control (ABC) method for optical in-phase and quadrature modulators (IQM) is proposed using digital chaotic waveform as dither signals. Two distinct chaotic signals, each with unique initial values, are introduced to the direct current (DC) port of IQM in conjunction with a DC voltage. Due to the robust autocorrelation performance and exceptionally low cross-correlation of chaotic signals, the proposed scheme is capable of mitigating the impact of low-frequency interference, signal-signal beat interference, and high-power RF-induced noise on transmitted signals. In addition, due to the broadwidth of chaotic signals, their power is distributed across a broad frequency range, resulting in a significant reduction in power spectral density (PSD). Compared to the conventional single-tone dither-based ABC method, the proposed scheme exhibits a reduction in peak power of the output chaotic signal by over 24.1 dB, thereby minimizing disturbance to the transmitted signal while maintaining superior accuracy and stability for ABC. The performance of ABC methods, based on single-tone and chaotic signal dithering, are experimentally evaluated in both 40Gbaud 16QAM and 20Gbaud 64QAM transmission systems. The results indicate that the utilization of chaotic dither signals leads to a reduction in measured bit error rate (BER) for 40Gbaud 16QAM and 20Gbaud 64QAM signals, with respective decreases from 2.48% to 1.26% and from 5.31% to 3.35% when the received optical power is -27dBm.

SNR-enhanced and high-order frequency multiplied 64-QAM millimeter-wave signal generation enabled by MZM-based angle modulation.

We propose and experimentally demonstrate a novel scheme to generate ultrahigh-order frequency multiplied millimeter-wave (mm-wave) signals with high fidelity enabled by angle modulation (ANG-M). The constant envelope (CE) characteristic of the ANG-M signal makes it possible to avoid nonlinear distortion induced by photonic frequency multiplication. In addition, the theoretical formula and the simulation results prove that the modulation index (MI) of the ANG-M signal increases along with frequency multiplication, so as to improve the signal-to-noise ratio (SNR) of the frequency-multiplied signal. In the experiment, we confirm the SNR of the 4-fold signal is enhanced by 2.1 dB approximately for the increased MI compared to the 2-fold signal. Finally, a 6-Gb/s 64-QAM signal with a carrier frequency of 30 GHz is generated and transmitted over 25-km standard single-mode fiber (SSMF) using only a 3-GHz radio frequency signal and 10-GHz bandwidth Mach-Zehnder modulator. To the best of our knowledge, it is the first time that a 10-fold frequency-multiplied 64-QAM signal with high fidelity is generated. The results prove that the proposed method will be a potential solution for low-cost mm-wave signal generation in future 6G communication.

Novel intrinsic factor Yun maintains female germline stem cell fate through Thickveins.

Germline stem cells (GSCs) are critical for the reproduction of an organism. The self-renewal and differentiation of GSCs must be tightly controlled to avoid uncontrolled stem cell proliferation or premature stem cell differentiation. However, how the self-renewal and differentiation of GSCs are properly controlled is not fully understood. Here, we find that the novel intrinsic factor Yun is required for female GSC maintenance in Drosophila. GSCs undergo precocious differentiation due to de-repression of differentiation factor Bam by defective BMP/Dpp signaling in the absence of yun. Mechanistically, Yun associates with and stabilizes Thickveins (Tkv), the type I receptor of Dpp/BMP signaling. Finally, ectopic expression of a constitutively active Tkv (TkvQD) completely suppresses GSC loss caused by yun depletion. Collectively, these data demonstrate that Yun functions through Tkv to maintain GSC fate. Our results provide new insight into the regulatory mechanisms of how stem cell maintenance is properly controlled.

Phosphorylation of Yun is required for stem cell proliferation and tumorigenesis.

Stem cells maintain adult tissue homeostasis under physiological conditions. Uncontrolled stem cell proliferation will lead to tumorigenesis. How stem cell proliferation is precisely controlled is still not fully understood. Phosphorylation of Yun is essential for ISC proliferation. Yun is essential for the proliferation of normal and transformed intestinal stem cells. Our mass spectrometry and biochemical data suggest that Yun can be phosphorylated at multiple residues in vivo. Interestingly, we show that the phosphorylation among these residues is likely interdependent. Furthermore, phosphorylation of each residue in Yun is important for its function in ISC proliferation regulation. Thus, our study unveils the important role of post-translational modification of Yun in stem cell proliferation.

Auxilin regulates intestinal stem cell proliferation through EGFR.

Adult tissue homeostasis is maintained by residential stem cells. The proliferation and differentiation of adult stem cells must be tightly balanced to avoid excessive proliferation or premature differentiation. However, how stem cell proliferation is properly controlled remains elusive. Here, we find that auxilin (Aux) restricts intestinal stem cell (ISC) proliferation mainly through EGFR signaling. aux depletion leads to excessive ISC proliferation and midgut homeostasis disruption, which is unlikely caused by defective Notch signaling. Aux is expressed in multiple types of intestinal cells. Interestingly, aux depletion causes a dramatic increase in EGFR signaling, with a strong accumulation of EGFR at the plasma membrane and an increased expression of EGFR ligands in response to tissue stress. Furthermore, Aux co-localizes and associates with EGFR. Finally, blocking EGFR signaling completely suppresses the defects caused by aux depletion. Together, these data demonstrate that Aux mainly safeguards EGFR activation to keep a proper ISC proliferation rate to maintain midgut homeostasis.

Temperature-Dependent Group Delay of Photonic-Bandgap Hollow-Core Fiber Tuned by Surface-Mode Coupling.

Surface modes (SM) are highly spatially localized modes existing at the core-cladding interface of photonic-bandgap hollow-core fiber (PBG-HCF). When coupling with SM, the air modes (AM) in the core would suffer a higher confinement loss despite being spectrally within the cladding photonic bandgap, and would be highly dispersive around the avoided crossing (anti-crossing) wavelength. In this paper, we numerically explored how such avoided crossings can play an important role in the tuning of the temperature dependence of group delay of AM of PBG-HCF. At higher temperatures, both the thermo-optic effect and thermal expansion contribute to the redshift of avoided crossing wavelength, giving rise to a temperature dependence of the AM dispersion. Numerical simulations show that the redshift of avoided crossing can significantly tune the thermal coefficient of delay (TCD) of PBG-HCF from -400 ps/km/K to 400 ps/km/K, approximately -120 ppm/K to 120 ppm/K. In comparison with the known tuning mechanism by thermal-induced redshift of photonic bandgap [Fokoua et al., Optica 4, 659, 2017], the tuning of TCD by SM coupling presents a much broader tuning range and higher efficiency. Our finding may provide a new route to design PBG-HCF for propagation time sensitive applications.

The Yun/Prohibitin complex regulates adult Drosophila intestinal stem cell proliferation through the transcription factor E2F1.

Stem cells constantly divide and differentiate to maintain adult tissue homeostasis, and uncontrolled stem cell proliferation leads to severe diseases such as cancer. How stem cell proliferation is precisely controlled remains poorly understood. Here, from an RNA interference (RNAi) screen in adult Drosophila intestinal stem cells (ISCs), we identify a factor, Yun, required for proliferation of normal and transformed ISCs. Yun is mainly expressed in progenitors; our genetic and biochemical evidence suggest that it acts as a scaffold to stabilize the Prohibitin (PHB) complex previously implicated in various cellular and developmental processes and diseases. We demonstrate that the Yun/PHB complex is regulated by and acts downstream of EGFR/MAPK signaling. Importantly, the Yun/PHB complex interacts with and positively affects the levels of the transcription factor E2F1 to regulate ISC proliferation. In addition, we find that the role of the PHB complex in cell proliferation is evolutionarily conserved. Thus, our study uncovers a Yun/PHB-E2F1 regulatory axis in stem cell proliferation.

DNA N6-methyladenine involvement and regulation of hepatocellular carcinoma development.

DNA N6-methyladenine (6 mA) is a new type of DNA methylation identified in various eukaryotic cells. However, its alteration and genomic distribution features in hepatocellular carcinoma (HCC) remain elusive. In this study, we found that N6AMT1 overexpression increased HCC cell viability, suppressed apoptosis, and enhanced migration and invasion, whereas ALKBH1 overexpression induced the opposite effects. Further, 23,779 gain-of-6 mA regions and 11,240 loss-of-6 mA regions were differentially identified in HCC tissues. The differential gain and loss of 6 mA regions were considerably enriched in intergenic regions. Moreover, 7% of the differential 6 mA modifications were associated with tumors, with 60 associated with oncogenes and 57 with tumor suppressor genes (TSGs), and 17 were common to oncogenes and TSGs. The candidate genes affected by 6 mA were filtered by gene ontology (GO) and RNA-seq. Using quantitative polymerase chain reaction (qPCR), BCL2 and PARTICL were found to be correlated with DNA 6 mA in certain HCC processes.

Derlin-1 and TER94/VCP/p97 are required for intestinal homeostasis.

Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its C-terminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1- or TER94-deficient progenitors. Further removal of reactive oxygen species (ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance (ER protein quality control) in tissue homeostasis and tumor development.

Identification of a new allele of O-fucosyltransferase 1 involved in Drosophila intestinal stem cell regulation.

Adult stem cells are critical for the maintenance of tissue homeostasis. However, how the proliferation and differentiation of intestinal stem cells (ISCs) are regulated remains not fully understood. Here, we find a mutant, stum 9-3, affecting the proliferation and differentiation of Drosophila adult ISCs in a forward genetic screen for factors regulating the proliferation and differentiation ISCs. stum 9-3 acts through the conserved Notch signaling pathway, upstream of the S2 cleavage of the Notch receptor. Interestingly, the phenotype of stum 9-3 mutant is not caused by disruption of stumble (stum), where the p-element is inserted. Detailed mapping, rescue experiments and mutant characterization show that stum 9-3 is a new allele of O-fucosyltransferase 1 (O-fut1). Our results indicate that unexpected mutants with interesting phenotype could be recovered in forward genetic screens using known p-element insertion stocks.

Autophagy induction in tumor surrounding cells promotes tumor growth in adult Drosophila intestines.

During tumorigenesis, tumor cells interact intimately with their surrounding cells (microenvironment) for their growth and progression. However, the roles of tumor microenvironment in tumor development and progression are not fully understood. Here, using an established benign tumor model in adult Drosophila intestines, we find that non-cell autonomous autophagy (NAA) is induced in tumor surrounding neighbor cells. Tumor growth can be significantly suppressed by genetic ablation of autophagy induction in tumor neighboring cells, indicating that tumor neighboring cells act as tumor microenvironment to promote tumor growth. Autophagy in tumor neighboring cells is induced downstream of elevated ROS and activated JNK signaling in tumor cells. Interestingly, we find that active transport of nutrients, such as amino acids, from tumor neighboring cells sustains tumor growth, and increasing nutrient availability could significantly restore tumor growth. Together, these data demonstrate that tumor cells take advantage of their surrounding normal neighbor cells as nutrient sources through NAA to meet their high metabolic demand for growth and progression. Thus we provide insights into our understanding of the mechanisms underlying the interaction between tumor cells and their microenvironment in tumor development.

Exosome-mediated miRNA delivery promotes liver cancer EMT and metastasis.

The deregulation of exosomal microRNAs (miRNAs) plays an important role in the progression of hepatocarcinogenesis. In this study, we highlight exosomes as mediators involved in modulating miRNA profiles in liver cancer cells after induction of the epithelial-mesenchymal transition (EMT) and metastasis. Initially, we induced EMT in a hepatocellular carcinoma cell (HCC) line (Hep3B) by stimulation with transforming growth factor-ß (TGF-ß) and confirmed by western blot detection of EMT markers such as vimentin and E-cadherin. Exosomes were then isolated from the cells and identified by nanoparticle tracking analysis (NTA). The isolated exosomal particles from unstimulated Hep3B cells (Hep3B exo) or TGF-ß-stimulated EMT Hep3B cells (EMT-Hep3B exo) contained higher levels of exosome marker proteins, CD63 and TSG101. After incubation with EMT-Hep3B exo, Hep3B cell proliferation increased. EMT-Hep3B exo promoted the migration and invasion of Hep3B and 7721 cells. High-throughput sequencing of miRNAs and mRNA within the exosomes showed 119 upregulated and 186 downregulated miRNAs and 156 upregulated and 166 downregulated mRNA sequences in the EMT-Hep3B exo compared with the control Hep3B exo. The most differentially expressed miRNAs and target mRNA sequences were validated by RT-qPCR. Based on the known miRNA targets for specific mRNA sequences, we hypothesized that GADD45A was regulated by miR-374a-5p. Inhibition of miR-374a-5p in Hep3B cells resulted in exosomes that inhibited the proliferation, migration, and invasion of HCC cells. These results enhance our understanding of metastatic progression of liver cancer and provide a foundation for the future development of potential biomarkers for diagnosis and prognosis of hepatic cancer.

Stent placement with iodine-125 seeds strand effectively extends the duration of stent patency and survival in patients with unresectable malignant obstructive jaundice.

Background: This study aimed to compare the treatment outcomes and safety between stent placement with or without Iodine-125 (125I) seeds strand for patients with unresectable malignant obstructive jaundice (MOJ).Methods: A total of 84 patients with unresectable MOJ treated in our hospital were retrospectively included and divided into the stent group (n = 54) undergoing biliary stent placement and the stent + seeds group (n = 30) receiving stent placement with 125I seeds strand. The therapeutic outcome, postoperative complications, duration of patient survival and stent patency were compared between groups. Kaplan-Meier survival analysis was performed to compare the duration of patient survival and stent patency between groups. Cox-regression analysis was performed to investigate predictive factors for disease-free survival and overall survival.Results: The stent + seeds group had significantly longer duration of patency (231.57 ± 256.54 vs. 110.37 ± 120.52) and overall survival (310.57 ± 330.54 vs. 173.15 ± 219.40) than the stent group (both p < .05). In addition, Kaplan-Meier survival analysis confirmed that the stent + seeds group had longer duration of patency (log-rank test, p = .001) and higher overall survival rate (log-rank test, p = .020) than the stent group. Furthermore, Cox-regression analysis demonstrated that treatment methods was an independent factor associated with disease-free survival (HR: 0.36, 95% CI: 0.19-0.70; p = .003) and overall survival (HR: 1.01, 95% CI: 1.00-1.01; p < .001).Conclusion: The stent placement with 125I seeds strand can significantly improve the primary patency rate and overall survival time in MOJ patients.

Large mode area microstructured fiber supporting 56 super-OAM modes.

In this paper, a kind of super-mode orbital angular momentum microstructured fiber (SM-OAM-MSF) is proposed. By introducing 20 Ge-doped equiangular cylindrical inclusions in the ring-core region, mode coupling mechanism is employed in the formation of super-OAM (SOAM) modes. Specifically, the double degenerated out-of-phase SMs are first generated by the coupling of individual core mode, then the quadruple degenerated SOAM modes are formed by combining two components of the out-of-phase SMs with a phase difference of ±π/2. Theoretical analysis and numerical results reveal that the effective index difference (Δneff) between adjacent out-of-phase SM groups are strongly influenced by the parameters of the individual core except the ring-core's width. Therefore, large mode area and SOAM modes' index separation larger than 1.0×10-4 can be achieved simultaneously in our proposed SM-OAM-MSF. Through careful fiber design, HE1,1 and HE2,1 are used in the formation of SMs and SOAM modes. Simulations show that all the nine SOAM groups originating from HE1,1 mode and the first five SOAM groups stemming from normal coupling of HE2,1 mode can be supported above 1.0µm, that are 56 SOAM modes in total. The highest purity is 99.86% for SOAM±2,1±,5 mode. And the maximum mode area (Aeff) value reaches up to 638.88µm2 at 1.55µm, which is nearly eight times larger compared to that of conventional ring-core MSFs.

Transarterial chemoembolization with pirarubicin-eluting microspheres in patients with unresectable hepatocellular carcinoma: Preliminary results.

PURPOSE: To present the early results of pirarubicin-eluting microsphere transarterial chemoembolization (PE-TACE) for patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We retrospectively analyzed 55 consecutive patients with HCC who received PE-TACE between April 1, 2015 and August 30, 2016. The complication rate, tumor response rate, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Adverse events were generally mild and included abdominal pain and fever, although a major complication was reported in 1 patient (1.8%). During a median follow-up of 10.0 months (range, 3.0-24.0 months), 14 patients (25.5%) achieved a complete tumor response, 25 (45.5%) had a partial response, 9 (16.4%) showed stable disease, and 7 (12.7%) had disease progression. The 1-month overall response rate was 70.9%, and the local tumor response rate was 89.0%. The 1-month tumor response rate was 100% for Barcelona Clinic Liver Cancer (BCLC) stage A or B disease and 62.8% for BCLC stage C disease. The median PFS was 6.1 months (95% confidence interval [95%CI], 3.4-8.8 months; range, 1.0-24.0 months). The median OS was 11.0 months (95%CI, 7.1-14.9 months; range, 2.0-24.0 months). Kaplan-Meier analysis (log-rank test) found significant differences in OS between patients grouped by tumor number (P = 0.006), tumor size (P = 0.035), and Eastern Cooperative Oncology Group (ECOG) score (P = 0.005). The tumor number (1 vs. ≥2) was the only factor independently associated with OS (hazard ratio [HR], 2.867; 95%CI, 1.330-6.181; P = 0.007). CONCLUSIONS: PE-TACE for unresectable HCC may be safe, with favorable tumor response rates and survival time, especially in patients with a single large tumor. Longer follow-up using a larger series is necessary to confirm these preliminary results.