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PURPOSE To investigate the efficacy of PD-1/PD-L1 inhibitors plus chemotherapy versus anti–PD-1/PD-L1 monotherapy in advanced microsatellite instability (MSI)/mismatch repair-deficient (dMMR) gastrointestinal cancers. METHODS We retrospectively recruited patients with MSI/dMMR gastrointestinal cancer who received anti–PD-1/PD-L1 with or without chemotherapy and compared objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of PD-1/PD-L1 inhibitor plus chemotherapy (chemo-anti–PD-1/PD-L1 group) and PD-1/PD-L1 inhibitor alone (anti–PD-1/PD-L1 group). Propensity score–based overlap weighting analysis was conducted to adjust the baseline covariable imbalance. Sensitivity analysis was performed to confirm the stability of the results by propensity score matching and multivariable Cox and logistic regression models. RESULTS A total of 256 patients were eligible, with 68 and 188 receiving chemo-anti–PD-1/PD-L1 and anti–PD-1/PD-L1, respectively. The chemo-anti–PD-1/PD-L1 group showed significant improvements versus the anti–PD-1/PD-L1 group in ORR (61.8% v 38.8%; P = .001), DCR (92.6% v 74.5%; P = .002), PFS (median PFS [mPFS], not reached [NR] v 27.9 months; P = .004), and OS (median OS [mOS], NR v NR; P = .014). After overlap weighting, the improvements tended to be more significant with chemo-anti–PD-1/PD-L1 versus anti–PD-1/PD-L1 in ORR (62.5% v. 38.3%; P < .001), DCR (93.8% v 74.2%; P < .001), PFS (mPFS, NR v 26.0 months; P = .004), and OS (mOS, NR v NR; P = .010). These results were solidified through sensitivity analysis. CONCLUSION Chemo-anti–PD-1/PD-L1 is superior to anti–PD-1/PD-L1 in MSI/dMMR gastrointestinal cancers with improved efficacy.

A nine-gap extended interaction oscillator (EIO) circuit capable of continuous multimode operation is proposed to overcome the continuous electronic tuning range limitation of the conventional single-mode operation EIO circuit. Circuit analysis shows that it has the capability of stable continuous mode switching between multiple operating modes with the sweeping operating voltage. Particle-in-cell simulation shows that a continuous mode switching between the π /8 mode and the 2π mode is achieved with a continuous electronic tuning range of 95.50-96.23 GHz. Working mechanism of the continuous multimode operation is preliminary studied by the ``cold cavity'' and ``hot cavity'' analysis.

The dispersion and dielectric attenuation characteristics of a double-staggered grating waveguide (DSGW) are two crucial features related to the output characteristics of a sheet-beam traveling-wave amplifier and have been previously studied by using theoretical analysis and simulations. In this work, these two characteristics are both experimentally studied. Two ${H}$ -band (220–325 GHz) DSGW circuit prototypes with and without dielectric attenuators made of the BeO-TiO2 composite ceramic were machined by using nanocomputer numerical control milling. Experimental studies of the dispersion property were performed successfully where the measurement results were in good agreement with those predicted by simulations, exhibiting a wide passband of 70 GHz (230–300 GHz). The measured transmission coefficient has been decreased from −5 to −55 dB after the introduction of dielectric attenuators, experimentally verifying the feasibility of the adopted methodology. The effects of the variations of dispersion relation and transmission loss on the beam-wave interaction stability were also investigated.

Background Increasing studies focused on the regulatory roles of circular RNAs (circRNAs) in diverse cancers. This study was to evaluate the function and mechanism of circRNA Scm-like with four malignant brain tumor domains 2 (circ-SFMBT2) in esophageal cancer (EC). Methods The circ-SFMBT2, microRNA-107 (miR-107) and solute-linked carrier family A1 member 5 (SLC1A5) levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was evaluated by 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay, colony formation assay and EdU assay. Cell apoptosis and invasion were detected by flow cytometry and transwell assay. Glutamine metabolism was assessed by the corresponding kits for glutamine consumption, α-ketoglutarate production and glutamate production. Western blot was used for protein quantification. The binding analysis was performed using dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and pull-down assays. The functional research of circ-SFMBT2 in vivo was performed by xenograft tumor assay. Exosomes were identified by morphological observation and protein detection. Results Circ-SFMBT2 was overexpressed in EC samples and cells. Circ-SFMBT2 downregulation inhibited EC cell proliferation, invasion and glutamine metabolism. Circ-SFMBT2 targeted miR-107 and the regulation of circ-SFMBT2 was achieved by sponging miR-107. SLC1A5 was a target of miR-107, and it worked as an oncogene in EC cells. MiR-107 retarded the EC progression by downregulating SLC1A5. Circ-SFMBT2 could affect the SLC1A5 expression by targeting miR-107. Circ-SFMBT2 regulated EC progression in vivo by miR-107/SLC1A5 axis. Circ-SFMBT2 was transferred by exosomes in EC cells. Conclusion These results suggested that circ-SFMBT2 upregulated the SLC1A5 expression to promote the malignant development of EC by serving as a miR-107 sponge.

Oxaliplatin (OXA) is a first-line chemotherapy drug for gastric cancer. We aimed to investigate the effect of circ 0008253, contained in M2 polarized macrophage-derived exosomes, on OXA resistance of gastric carcinoma cells. Flow cytometry was performed to detect the differentiation of macrophages and cell apoptosis. Cell Counting Kit-8 assay was conducted to examine the cell viability. Transmission electron microscopy, Nanoparticle Tracking Analysis, Western bolt, and Immunofluorescence were carried out. Cell proliferation was detected with a colony formation experiment. Levels of CD206, Arg1, IL-10, and TGF-β were increased in M2 polarized macrophages. Cell viability was decreased gradually with the increase of time and OXA concentration. Apoptosis of gastric carcinoma cells was decreased after co-culture with M2-polarized macrophages. Exosomes isolated from M2-polarized macrophages (M2-Exos) could be co-located with gastric carcinoma cells. M2-Exos enhanced drug resistance, reduced apoptosis and OXA resistance. Bioinformatics analysis showed that circ 0008253 could be transferred from M2-Exos to gastric carcinoma cells. Overexpressing circ 0008253 increased cell viability, tumor size, and ABCG2 levels, decreased OXA sensitivity. Circ 0008253, contained in M2-Exos, was directly transferred from tumor-associated macrophage to gastric carcinoma cells, finally enhancing OXA resistance.

Patients with biliary tract cancer (BTC) were associated with poor prognosis and limited therapeutic options after first-line therapy currently. In this study, we sought to evaluate the feasibility and tolerability of sintilimab plus anlotinib as the second-line treatment for patients with advanced BTC. Eligible patients had histologically confirmed locally advanced unresectable or metastatic BTC and failed after the first-line treatment were recruited. The primary endpoint was overall survival (OS). Simultaneously, association between clinical outcomes and genomic profiling and gut microbiome were explored to identify the potential biomarkers for this regimen. Twenty patients were consecutively enrolled and received study therapy. The trail met its primary endpoint with a median OS of 12.3 months (95% CI: 10.1-14.5). Only four (20%) patients were observed of the grade 3 treatment-related adverse events (TRAEs) and no grade 4 or 5 TRAEs were detected. Mutation of AGO2 was correlated with a significantly longer OS. Abundance of Proteobacteria was associated with inferior clinical response. Therefore, sintilimab plus anlotinib demonstrated encouraging anti-tumor activity with a tolerable safety profile and deserved to be investigated in larger randomized trials for patients with advanced BTC subsequently.

Background: In microsatellite instability (MSI)/mismatch repair-deficient (dMMR) gastrointestinal cancers, the optimum therapy after the progression of immune checkpoint inhibitors (ICIs) is yet unknown. Here, we compared the efficacy of programmed death 1 (PD1)/programmed death ligand-1 (PD-L1) inhibitors plus other therapy and chemotherapy with or without targeted therapy in MSI/dMMR gastrointestinal cancer patients after progression on anti-PD1/PD-L1 monotherapy. Methods: We retrospectively recruited MSI/dMMR gastrointestinal cancer patients who had progressed on anti-PD1/PD-L1 monotherapy. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and PFS ratio (PFSr) were compared between patients who received anti-PD1/PD-L1 plus other therapy (ICI-plus group) and patients who received chemotherapy with or without targeted therapy (chemo-targeted group). Results: In total, 26 and 25 patients were recruited in the ICI-plus group and chemo-targeted group, respectively. Significantly better DCR (80.8% vs. 44.0%, p = 0.007), PFS (median PFS 6.9 months vs. 3.0 months, p = 0.001), OS (median OS NR vs. 14.1 months, p = 0.043), and PFSr (2.4 vs. 0.9, p = 0.021), along with a numerically higher ORR (23.1% vs. 12.0%, p = 0.503) were observed in the ICI-plus group compared with the chemo-targeted group. Multivariate analyses identified the therapy regimen as an important prognostic factor in gastrointestinal cancers. Conclusions: Compared to conventional chemotherapy with or without targeted therapy, continuing anti-PD1/PD-L1 in combination with other treatments showed better clinical outcomes in MSI/dMMR gastrointestinal cancer patients who progressed on PD1/PD-L1 blockade, which should be validated prospectively in clinical trials.

Normally, the conventional sheet beam extended interaction oscillator (SB-EIO) operates in a single mode and has a narrow tunable bandwidth. To broaden the tunable bandwidth, the concept of multiple-mode operation is proposed and a 0.3-THz ladder-shaped interaction circuit is designed as described in this article. The interaction circuit was manufactured by using the computer numerical control milling technique and cold tested by using a vector network analyzer. Measured and simulated results were in good agreement with each other. Beam-wave interaction simulations with the ohmic loss being taken into account verified the feasibility of the multiple-mode operation and demonstrated that the SB-EIO produced an output power of >91 W in the frequency range of 293.7–294.9 GHz. Compared with the single-mode SB-EIO, the tunable bandwidth of the multiple-mode SB-EIO has increased from 0.3 to 1.2 GHz.

For extended interaction structure devices (EIDs), the determinants of field flatness are analyzed. It is found that the flatness of field distribution is determined by a cutoff condition existing in EIDs, which is based on the concepts of both resonant cavity and wave propagation. Such an analytical conclusion is verified by a novel scheme for the measurement of field distribution in an extended interaction oscillator (EIO) based on the perturbation technique. The sinusoidal-like axial field components with different flatness are obtained by utilizing the measured frequency shifts. Based on the cutoff condition, three field distribution patterns are established, including middle-concentrated, flat-distributed, and side-concentrated types. Particle-in-cell (PIC) simulations of a ${W}$ -band EIO show that three field distribution patterns have the advantages of low surface-loss power, high power-capacity, and low oscillating-threshold, respectively.

Soy meal-based wood adhesive has received much interest for its environmentally friendly properties, as it is thought to provide an effective alternative to conventional formaldehyde-based wood adhesives. However, the abundant hydrophilic groups and weak internal structure result in poor water resistance and low bonding strength of soy meal-based wood adhesives. In this study, bio-based carboxymethylated wood fibers (CMWFs) were used to develop a high-performance soy meal-based adhesive. Wood fibers (WFs) were pre-treated via carboxymethylation to endow WFs with abundant carboxyl groups and facilitate their dispersion in soy protein matrix. CMWFs containing abundant carboxyl groups served as a multiple “crosslinking core” and effectively cross-linked with soy protein side-chain, resulting in the construction of a stable adhesive system. The modified soy meal-based adhesive exhibited excellent bonding strength and water resistance. In particular, tension tests indicated that the water-resistant bonding strength of the adhesive modified with CMWFs reached 1.69 MPa, which was 160% higher compared with the unmodified adhesive; the wood failure percentage of the plywood bonded by CMWF-modified soy meal-based adhesive was as high as 100%. Moisture uptake and residual rate tests indicated that high water resistance of the adhesive was achieved. This design provides a facile and sustainable strategy for developing high-performance soy meal-based adhesives.

Introduction Long non-coding RNA (lncRNA) was reported to be a crucial regulator in cancer. In this work, our purpose is to explore the biolog ical roles of nuclear paraspeckle assembly transcript 1 (NEAT1) in gastric cancer (GC). Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect NEAT1 expression in GC cells and normal cells. GC cell behaviors after NEAT1 overexpression or downregulation were analyzed by Cell Counting Kit-8 assay, colony formation assay, wound-healing assay, and flow cytometry assay. Bioinformatic tools were used to analyze the significance of NEAT1 in GC. The involvement of microRNA-365a-3p (miR-365a-3p) and ATP -binding cassette subfamily C member 4 (ABCC4) in the biological roles of NEAT1 in GC progression was validated by luciferase activity reporter assay and rescue experiments. Results We found NEAT1 increased expression in both GC tissues and cells and correlated with poorer overall survival of cancer patients. We found NEAT1 overexpression promotes, while its knockdown inhibits GC cell proliferation, colony formation, invasion, and cell cycle progression in vitro. Mechanism analyses showed that NEAT1 serves as a ceRNA to upregulate ABCC4 expression via sponging miR-365a-3p. Conclusion In this study, we revealed a NEAT1/miR-365a-3p/ABCC4 triplet in GC progression, which may provide novel targeted therapy markers for GC.

Fiber agglomeration and poor interfacial combination with the matrix restrict the performance of composites. Herein, soybean meal-based adhesives were fabricated via the addition of dialdehyde cellulose (DAC) obtained from waste paper dissolved in an alkali–urea system and oxidized with sodium periodate. Due to the dissolution by the alkali–urea system, DAC dispersed well in the solution and did not aggregate in the adhesive matrix. Because of the oxidation treatment, DAC was crosslinked with the adhesive matrix via a Schiff base reaction. Meanwhile, hydrogen bonds were formed at the interface between the DAC and the adhesive matrix. Plywood with the SM/DAC/PTGE adhesive reached its highest wet bonding strength of 1.27 MPa (4 wt% DAC addition), a 95% increase compared to that with the unmodified SM/PTGE adhesive. Fine DAC-to-SM interfacial bonding and a dense crosslinking network were constructed in the SM/DAC/PTGE adhesive systems. The cycle of reuse for the alkali–urea system in the experiments demonstrated that the preparation method of the cellulose solution was scalable and sustainable.

A large amount of sulfur dioxide (SO2) will be released during rural household coal combustion, causing serious environmental pollution. Therefore, it is very urgent to develop a clean and efficient fuel to substitute rural household coal controlling SO2 emission. In this paper, a new strategy toward scattered coal combustion with remarkably reducing SO2 emission was proposed. Coal and compound additive of Al2O3 and CaCO3 were blended and then copyrolysis at 1050 °C was performed to produce clean coke. First, the sulfur content of clean coke was reduced, meanwhile, generating sulfur fixation precursor during pyrolysis. Then, clean coke is used for efficient sulfur fixation during the subsequent combustion process to reduce SO2 emissions. The effects of combustion temperature, Al/S molar ratio, and the mechanism of sulfur retention during clean coke combustion were studied in the tube furnace and muffle furnace. The mechanism can be attributed the following reason: (a) CaS produced during pyrolysis and CaO decomposed by complex additives were oxidized during combustion, and CaO captured the SO2 released from clean coke combustion, which formed CaSO4. (b) CaSO4 reacts with Al2O3 to produce calcium sulfoaluminate at high temperatures, which improves the sulfur fixation efficiency of clean coke combustion at high temperatures. In a word, this new strategy can greatly reduce the emission of SO2, thus helping to solve rural household coal pollution problems.

Objective: There are no comprehensive studies on survival outcomes and optimal treatment protocols for cervical esophageal cancer (CEC), due to its rare clinical prevalence. Our objective was to determine the relationship between pathological characteristics, treatment protocols, and survival outcomes in Chinese CEC patients. Methods: A total of 500 Chinese CEC patients were selected from our 500,000 esophageal and gastric cardia carcinoma database (1973–2018). There were two main groups: patients treated with surgery, and patients receiving non-surgical treatments (radiotherapy, radiochemotherapy, and chemotherapy). The Chi-square test and Kaplan–Meier method were used to compare the continuous variables and survival. Results: Among the 500 CEC patients, 278 (55.6%) were male, and the median age was 60.9 ± 9.4 years. A total of 496 patients (99.2%) were diagnosed with squamous cell carcinoma. In 171 (34.2%) patients who received surgery, 22 (12.9%) had undergone laryngectomy. In 322 (64.4%) patients who received non-surgical treatments, 245 (76.1%) received radiotherapy. Stratified survival analysis showed that only T stage was related with survival outcomes for CEC patients in the surgical group, and the outcomes between laryngectomy and non-laryngectomy patients were similar. It was noteworthy that the 5-year survival rate was similar in CEC patients among the different groups treated with surgery, radiotherapy, chemotherapy, or radiochemotherapy (P = 0.244). Conclusions: The CEC patients had similar survival outcomes after curative esophagectomy and radiotherapy, including those with or without total laryngectomy. These findings suggest that radiotherapy could be the initial choice for treatment of Chinese CEC patients.

A dual-cavity extended interaction oscillator (EIO) is proposed to overcome the efficiency limitation and circuit instability of the conventional EIO (i.e., the single-cavity, strong-coupling EIO), and its advantages in efficiency and stability are demonstrated by the study of a dual-cavity, Ka -band, EIO circuit. Circuit characteristics of the weak-coupling and strong-coupling circuits are studied and the key design issues are analyzed. Efficiency improvement from 14.2% to 20.2% and from 16.8% to 21.7% is predicted by the 3-D particle-in-cell (PIC) simulations performed in CST and CHIPIC, respectively. Not only a high-efficiency dual-cavity EIO circuit is achieved, but also the stability and robustness are analyzed and improved. This design provides an effective approach toward efficiency and stability improvement in the millimeter-wave range, and analyses on the weak-coupling and strong-coupling circuits are practical for the extended interaction structure study.

310 Background: Compared to standard chemotherapy, immune checkpoint inhibitors monotherapy and combined with chemotherapy regimens have been shown significant benefits for patients with advanced or metastatic esophageal cancer in both second-line and first-line treatment, respectively. Anlotinib was an effective second-line monotherapy for esophageal squamous cell carcinoma in China and the combination of anlotinib and immunotherapy might be a promising strategy. The study aimed to investigate the efficacy and safety of anlotinib plus PD-1 inhibitors during the treatment of esophageal cancer in the real world setting. Methods: This is a multicenter real-world study in patients with unresectable locally advanced, recurrent or metastatic esophageal cancer, who would benefit from anlotinib plus a PD-1 inhibitor under the doctor's evaluation. The enrolled patients received treatment according to physicians. The primary endpoint was PFS, and secondary endpoints included ORR, DCR and OS. The response to treatment was evaluated according to RECIST version 1.1. In addition, adverse events were evaluated by CTCAE v5.0. Results: Between May 2020 and Sep 2022, 207 pts were enrolled. 109 comprised the evaluable population. In the full analysis set, 203 patients were squamous cell and 4 were adenocarcinoma histology. 137 of 207 (66.2%) pts were male. 44(21.3%) had an ECOG performance status of 0, 136 (65.7%) status of 1 and 27 (13.0%) status of ≥2. 47 pts had previously used anti-PD-1/PD-L1 antibody or vascular targeting drugs, of which 8 cases had combined anti-PD-1/PD-L1 antibody and vascular targeting drugs. Among the 109 evaluable pts, 17 (15.6%) pts received first-line therapy, 64 (58.7%) second-line and 28(25.7%) third & above line. Of which, 5 patients achieved complete response (CR), 32 pts partial response (PR), 62 pts stable disease (SD), illustrating an ORR of 34.0% (95%CI 25.1-43.6) and a DCR of 90.8%(95%CI 83.8-95.5). In the first line therapy, ORR was 47.1% and DCR was 88.2%. In the second line therapy, ORR was 32.8% and DCR was 96.9%. In the third & above line, ORR with 28.6% and DCR with 78.6% were observed. Median PFS was not reached, 6m-PFS rate was 87.9%. Treatment related adverse events (TRAEs) were reported in 55 pts (50.5%). 6 patients had grade 3 or more TRAEs. Conclusions: Anlotinib plus PD-1 inhibitors for advanced or metastatic esophageal cancer demonstrated a promising clinical benefit and a manageable safety profile. Further investigation in larger cohorts and even randomized controlled studies is warranted. Clinical trial information: NCT04966611 .

A W-band TE□ 40 mode converter with a compact structure based on three T-junction power dividers for measuring high-order overmoded mode slow-wave structures is presented. Since the T-junction discontinuity causes the port reflection, a series of matching steps were introduced in the converter. The proposed converter possessed a bandwidth of 12 GHz with the transmission coefficient S 21 higher than -3 dB and port reflection S 11 lower than -15 dB. More importantly, the transmission coefficient of the unwanted modes is lower than -15 dB within the bandwidth of interest.

Preliminary study of a TE20 input/output coupling structure for sheet electron beam traveling wave tubes is presented in this paper. A TE10-TE20 mode converter and a single branch waveguide coupler are used to realize the proposed design. Simulation results obtained by using the CST simulation software demonstrated that the port reflection and the transmission coefficient were respectively lower than - 15 dB and higher than - 1 dB in the frequency range of 241-298 GHz. The port isolation was lower than - 10 dB in the frequency range of 250-298 GHz.

In this paper, the circuit synthesis concept is applied to support a novel extended interaction RF circuit for generating a high-power millimeter-wave radiation. Its novel configuration is constructed by parallel connecting multiple sheet-beam-extended interaction cavities arranged along the angular direction to form a distributed hollow electron beam (HEB) as a whole. The specific concept endows the proposed circuit features such as: 1) making the diameter of HEB flexible and hence extending the space to set more single-sheet beam cavity in angular direction for increasing power capacity and 2) offering the opportunity to adopt a mutual magnetic focusing system for the distributed HEB, which is critical for the feasibility of the circuit synthesis. The circuit analysis is carried out, and a ${W}$ -band extended interaction oscillator (EIO) based on this concept is proposed to preliminarily demonstrate the capability of circuit synthesis. The distributed HEB is produced with an immersed electron gun using a 0.8 T focusing magnetic field. Simulations using 3-D particle-in-cell (PIC) technology in Computer Simulation Technology (CST) predict a peak output power up to 10.0 kW around 103 GHz with the beam current of 4.2 A at 27 kV.

Background and aim Standard chemotherapy has limited clinical efficacy in patients with esophageal cancer and there is a significant and unmet clinical need for effective treatment options for these patients. The aim of this study was to compare the clinical efficacy of the novel, targeted drug apatinib combined with docetaxel, and docetaxel combined with S-1 as second- or further-line treatment for patients with advanced esophageal cancer. Methods We enrolled 33 patients with advanced esophageal cancer in chemotherapy group or apatinib combined with chemotherapy group in this retrospective study. Apatinib (500 mg) was taken orally once daily; docetaxel was administered at a dose of 75 mg/m2; and S-1 was optional at a dose of 40-60 mg, based on body surface area. The primary endpoint of this study was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and the incidence and severity of adverse events (AEs). Results No complete response was observed in the two groups. However, two and five patients achieved partial response in the chemotherapy group and the apatinib combined with chemotherapy group, respectively. The ORR and DCR for the chemotherapy group was 11.1% and 33.3%, respectively. In the apatinib combination group, ORR and DCR was 88.9% and 93.3%, respectively. Anemia (11.1%) and neutropenia (5.6%) were the most frequent grade III/IV AEs observed in the chemotherapy group. In the apatinib combination group, the most frequent grade III/IV AEs were anemia (13.3%), hypertension (6.7%), and proteinuria (6.7%). Median PFS was significantly longer in the apatinib combination group than in the chemotherapy group (175 days vs 85 days, P=0.01). Conclusion The combination of apatinib and docetaxel has a manageable toxicity profile and may prolong survival. Therefore, this combination may be used as as second- or further-line treatment for patients with advanced esophageal cancer.

Background and aim Gastric cancer (GC), a malignant tumor worldwide, is mostly diagnosed at an advanced stage. We selected the oncogene encoding transcription factors MYBL2 to investigate the connection between MYBL2 expression and GC prognosis. Materials and methods MYBL2 mRNA and protein expression were measured by real-time PCR and immunohistochemistry, respectively. The relationship between MYBL2 protein expression and survival time was estimated by the Kaplan-Meier analysis. Cox proportional hazards model was used to evaluate the prognostic impact of MYBL2 expression. Results The overexpression of MYBL2 was related to tumor cell differentiation, Lauren type, and metastasis of lymph nodes (P

A stable high-order mode version of a ladder-type RF circuit (ladder cavity) is proposed to overcome the frequency limits of the commonly used fundamental mode counterpart for the development of millimeter-wave and higher frequency extended interaction oscillators (EIOs). The specific design for the stable operated circuit and its analysis based on the mode characteristic is carried out. The study of the transverse mode shows the potential of the TM31 mode in establishing more sufficient axial electric field than the fundamental TM11 version in a large size cavity. To enable the TM31 mode to overwhelm other possible competing modes in the circuit impedance, the field distribution of the TM31 mode is optimized in design through the analysis of transverse parameters. Key features that ensure stable operation are: 1) the large mode separation and nonoverlapping oscillation regions embodied in beam-loading conductance between related modes due to the specific design and 2) the large difference in the start-oscillation currents of the TM31 and TM11 modes based on the theoretical analysis. To demonstrate the circuit capability, a $W$ -band EIO with the proposed circuit has been designed. Simulations with a 3-D particle-in-cell code in CHIPIC predict a maximum output power over 10.6 kW around 93.1 GHz was obtained with a 20.5-kV and 8-A electron beam. The design provides a promising approach for making a stable high-order mode RF circuit applied in high-frequency EIOs.

e16052 Background: Immunotherapy, particularly with anti-PD-1/PD-L1 antibodies, has shown therapeutic efficacy in various malignancies. Compared with chemotherapy, anti-PD-1 antibody monotherapy improved the median overall survival in advanced or metastatic esophageal cancer. The combination of an anti-PD-1/PD-L1 antibody with an angiogenesis inhibitor has shown efficacy in many cancers which including esophageal cancer. The purpose of this study is to investigate the efficacy and safety of anlotinib plus PD-1 inhibitors as chemo-free therapy during the treatment of esophageal cancer in the real world setting. Methods: This prospective, multicenter real-world study (NCT04966611) evaluated the efficacy and safety of anlotinib plus PD-1 inhibitors in the chemo-free therapy setting for advanced or metastatic esophageal cancer patients (pts). Primary endpoint was evaluation of PFS (progression-free survival), and secondary endpoints included ORR (objective response rate), DCR (disease control rate) and OS (overall survival). The response to treatment was evaluated according to RECIST version 1.1. In addition, adverse events were evaluated by CTCAE v5.0. Results: Between May 2020 and Dec 2021, 50 pts were enrolled. 45 comprised the evaluable population. In the full analysis set, 44 had squamous cell and 1 patient had adenocarcinoma histology. 29 (64.4%) of 45 pts were male. 10 (22.2%) had an ECOG performance status of 0, 32 (71.1%) status of 1 and 3 (6.7%) status of 2. Twenty (44.4%) pts had distant metastases and 29(64.4%) pts had comorbidities. 15 pts had previously used anti-PD-1/PD-L1 antibody or vascular targeting drugs, of which 5 cases had combined the two drugs. Among all evaluable pts, 5(11.1%) pts received first-line, 27(60.0%) second-line and 13(28.9%) third & above line therapy. Among all pts, 1 patient achieved complete response (CR), 16 pts partial response (PR), 25 pts stable disease (SD), illustrating an ORR of 37.8% and a DCR of 93.3%. In the first line therapy, ORR was 60.0%, DCR was 100%.In the second line therapy, ORR was 37.0%, DCR was 96.3%. In the third & above line, ORR with 30.8%, DCR with 84.6% was observed. Median PFS was not reached. Treatment related adverse events (trAEs) were reported in 24 pts(53.3%). No patient had grade 3 or more trAEs. Conclusions: Anlotinib plus PD-1 inhibitors in chemo-free therapy for advanced or metastatic esophageal cancer was active and showed excellent tumor response and was generally well tolerated. Further investigation is required in a larger real-world cohort to validate the benefit of anlotinib plus PD-1 inhibitor in esophageal cancer. Clinical trial information: NCT04966611.