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Rapid and accurate identification of bacteria is essential to ensure food safety and prevent pathogenic bacterial infection. In this study, a highly efficient method was established for accurately identifying bacterial species by applying Ag NP-filter paper based Surface enhanced Raman spectroscopy (SERS) analysis and Partial Least Squares-Discriminant Analysis (PLS-DA) statistical methods. The flexible Ag NP filter paper substrate with high sensitivity and uniformity was prepared by a facile and low-cost silver mirror reaction at room temperature, which exhibited desirable SERS activity in bacteria detection. Furthermore, PLS-DA was successfully employed to distinguish SERS spectra from

Development of nanotheranostic agents with near-infrared (NIR) absorption offers an effective tool for fighting malignant diseases. Lanthanide ion neodymium (Nd

Background: Kariminejad and Scully reported 9 cases that were difficult to identify outside the ovary Tumors, located in the broad ligament, fallopian tube mesentery, and ovary, named female adnexal tumors of probable Wolffian origin. Aim: To investigate ultrasound images with female adnexal tumors of probable Wolffian origin (FATWOs). Case Report: We reported ultrasound images in three women with female adnexal tumors of probable Wolffian origin (FATWOs) with detailed discussion. Ultrasonography showed a predominantly-solid mass with clear-cut boundary with neighboring normal ovary at the left mesosalpinx (broad ligament) in both cases. Doppler examination presented moderate color content in both tumors. Conclusion: Ultrasound images may provide a clue for preoperative diagnosis of FATWOs.

Purpose: DNA damage repair (DDR) mutations are known to predict response to platinum-based chemotherapy in multiple solid tumors, as well as immunotherapy in non-small cell lung cancer (NSCLC). However, the predictive value of DDR in immunization combined with platinum chemotherapy remains unclear. Methods: We retrospectively collected information from 495 patients with advanced NSCLC whose tumors were analyzed using next-generation sequencing (NGS) and analyzed the characteristics of DDR mutations. Among them, 64 patients with NSCLC who received platinum chemotherapy and 37 patients who received immunotherapy combined with platinum chemotherapy were included in the prognostic analysis. Results: The DDR genes was commonly mutated in Chinese NSCLC population (242/495, 48.89%). In Chinese NSCLC cohort, DDR mutations showed a strong association with high tumor mutational burden (TMB-H) (DDR mutant vs DDR wild-type: 7.26 muts/Mb vs 5.15 muts/Mb, P=0.001) and higher rates of strong PD-L1 (TPS≥50%) positivity (DDR mutant vs DDR wild-type: 28.74% vs 20.69). Sixty-four advanced NSCLC patients treated with platinum-based chemotherapy were analyzed, the ORRs were 16% for the patients with DDR mutations (DDRmut) and 2.70% for the DDR wild-type (DDRwt) subgroup (P Conclusions: DDR mutations may serve as a positive predictor of immunization combined with platinum chemotherapy in patients with advanced NSCLC. Citation Format: Zhiwe Xiao, Lingling Sun, Yating Zheng, Hanrui Chen, Xinting Zheng, Jiamin Luo, Chuying Gu, Ruiting Lin, Xue Hu, Mengli Huang, Lizhu Lin. DNA damage repair gene mutations predict the efficacy of immunization combined with platinum chemotherapy in advanced non-small cell lung cancer: A retrospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5396.

A novel 3.3 kV rated 4H-SiC trench PiN (T-PiN) structure, which features a trench P+ layer, is proposed and experimentally demonstrated. For the T-PiNs, dry etch onto the N-drift layer is added to the manufacturing process of conventional PiNs (Con-PiNs) before the Al ion implantation step. As the experimental results show, the forward current of the T-PiN diode with an active area of 5 mm × 5 mm has been improved by 32.3% at a voltage of 4 V. Apart from a slight sacrifice in breakdown voltage, the T-PiN is identical to the Con-PiN with regard to other static and surge current capabilities and dynamic characteristics. This superior forward conduction ability of the T-PiNs is a result of enhanced anode carrier injection caused by an enhanced conductance modulation effect and a larger anode carrier injection area. An enhanced conductance modulation effect model was also set up to quantify the increase in the proportion of current density in the T-PiN.

In order to explore the specific mechanism of YiqiChutan formula (YQCTF) in inhibiting the angiogenesis of lung cancer and its relationship with delta-like ligand 4- (DLL4-) Notch signaling, 30 healthy BALB/c-nu/nu rats were selected and divided into three groups: A549 group (implanted with lung adenocarcinoma cell line A549), NCI-H460 group (implanted with human lung large-cell carcinoma cell line NCI-H460), and NCI-H446 group (implanted with human lung small cell carcinoma cell line NCI-H446) for constructing lung cancer transplanted tumor models. After modeling, the group treated with normal saline was taken as control group, 200 mg/kg of YQCTF was adopted for intervention, and the tumor volume and growth inhibition rate were compared with the vascular targeted inhibitor Sorafenib. HE staining, CD31 fluorescent antibody staining, and microelectron microscopy were adopted to observe the neovascular endothelial cells of the transplanted tumor. The expression of VEGF, HIF-1α, DLL4, and Notch-1 in the transplanted tumors in each group was detected by Western blot and RT-PCR at the protein level or mRNA level. Compared with the control group, the YQCTF-treated group had obvious inhibitory effect on lung cancer transplanted tumor and lung cancer angiogenesis. In the YQCTF-treated group, the density of angiogenesis decreased significantly and the vascular lumen structure also decreased, and the expression levels of VEGF, HIF-1α, DLL4, and Notch-1 in the YQCTF-treated group were all lower than those in the control group. YQCTF could inhibit the growth of lung cancer transplanted tumor through antiangiogenesis, and it could also reduce the amount of angiogenesis in lung cancer transplanted tumor. In addition, the generation of lumen structure was also hindered, which was realized through the VEGF signaling pathway and DLL4-Notch signaling pathway.

Color fundus image is the most basic way to diagnose diabetic retinopathy, papillary edema, and glaucoma. In particular, since observing the morphological changes of the optic disc is conducive to the diagnosis of related diseases, accurate and effective positioning and segmentation of the optic disc is an important process. Optic disc segmentation algorithms are mainly based on template matching, deformable model and learning. According to the character that the shape of the optic disc is approximately circular, this proposed research work uses Kirsch operator to get the edge of the green channel fundus image through morphological operation, and then detects the optic disc by HOUGH circle transformation. In addition, supervised learning in machine learning is also applied in this chapter. First, the vascular mask is obtained by morphological operation for vascular erasure, and then the SVM classifier is segmented by HU moment invariant feature and gray level feature. The test results on the DRIONS fundus image database with expert-labeled optic disc contour show that the two methods have good results and high accuracy in optic disc segmentation. Even though seven different assessment parameters (sensitivity [Se], specificity [Sp], accuracy [Acc], positive predicted value [Ppv], and negative predicted value [Npv]) are used for performance assessment of the algorithm. Accuracy is considered as the criterion of judgment in this chapter. The average accuracy achieved for the nine random test set is 97.7%, which is better than any other classifiers used for segmenting Optical Disc from Fundus Images.

BackgroundThis trail is an open-label, single-arm, phase II study that aims to observe the efficacy and safety of toripalimab combined with anlotinib and platinum-etoposide (EP) chemotherapy as first-line treatment in ES-SCLC (Clinical trial information: NCT04731909). The preliminary results of the study have been presented in 2020 ASCO abstract e20570, which demonstrated 100% objective response rate (ORR) and tolerable safety. Here we report PFS analysis results of the study.MethodsThe study enrolled treatment-naïve ES-SCLC patients (18–75 years, ECOG PS ≤2) who have measurable target lesion evaluated by RECIST v1.1. All enrolled patients received toripalimab (240 mg, d1) combined with etoposide (100 mg/m2, d1–3) plus carboplatin (AUC=5, d1)/cisplatin (75 mg/m2, d1) and anlotinib (12 mg QD, d1–14) of a 21-day cycle. After 4–6 cycles of the treatment, patients who achieved complete response (CR), partial response (PR) or stable disease (SD) could continue to receive maintenance therapy with toripalimab and anlotinib until disease progression. The primary endpoint was overall survival (OS). ORR, disease control rate (DCR), progression-free survival (PFS) and safety were set as secondary endpoints.ResultsAs of July 16, 2021, the median follow-up was 13.7 months. 9 disease progression events occurred of the enrolled 16 treatment-naïve ES-SCLC patients (14 males, 2 females, median age 63). The investigator-assessed median PFS was 13.3 months (95%CI: 5.0–21.6). The PFS rate at 6 months was 81.3% and the PFS rate at 12 months was 31.3%. 15 patients were still alive and the study treatments for 7 patients were still ongoing. At the data cutoff, there was only 1 patient dead with 37.6 months OS and the median OS was not reached. No new unexpected adverse events were observed.ConclusionsCombined with preliminary data at 2020 ASCO, toripalimab combined with anlotinib and EP chemotherapy showed excellent ORR and PFS as well as tolerable safety in treatment-naïve ES-SCLC. The combination therapy is expected to provide clinically meaningful OS benefit and become a promising treatment option.Trial RegistrationThis study is registered with ClinicalTrials.gov (National Institutes of Health), number NCT04731909.Ethics ApprovalThe program was approved by the ethics committee of Army Medical Center (Daping Hospital ).

Introduction: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and rapid spreading cancers. None of the existing therapies is optimum and most ATC patients experience rapid recurrence. The median overall survival (OS) of ATC patients is about 5 months. Here, we report an ATC patient, who experienced rapid recurrence after operation, achieved OS of 9 months by applying a novel strategy of combining anti-angiogenic agent, anlotinib with immunotherapeutic drug, sintilimab. Case presentation: The female ATC patient was 78 years old. On September 24, 2019, she had total thyroidectomy of the left lobe and isthmus due to a 4.7 cm × 4.2 cm lump in the left anterior cervical region. The mass was diagnosed as anaplastic thyroid cancer (pT3Nx). Immunohistochemistry and molecular testing analysis of the tumor showed the tumor proportion score of programmed death-ligand 1 Discussion: In this case, the novel anti-angiogenic drug anlotinib was chosen because it was proven to be safe and effective in treating multiple cancers without targeted mutations. Although the patient did not have positive indicators for immunotherapy (PD-L1 negative/TMB-low), we added sintilimab for the previous evidences of synergistic effect of anti-angiogenic drugs and immunotherapy in other cancers. Anti-angiogenic drug could increase the expression of immune cell markers including PD-L1; moreover, normalized tumor vasculature could increase the infiltration of immune cells. Here, our case provides supportive evidence for using this combination in the treatment of ATC patients. Conclusion: This case showed relatively good prognosis after using anti-angiogenic agent, anlotinib, and immunotherapeutic drug, sintilimab, suggesting a new direction in treating recurrent and inoperable ATC patients, and also providing a new way for cancer patients with PD-L1 negative/TMB-low. Citation Format: Shiheng Zhang, Yuntong Liu, Jiamin Luo, Yu Fang, Tonghui Ma, Xiaoyan Zhang, Wei Guan. An effective treatment for recurrent and inoperable anaplastic thyroid carcinoma using sintilimab and anlotinib: A case report [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 424.

Effector proteins delivered inside plant cells are powerful weapons for bacterial pathogens, but this exposes the pathogen to potential recognition by the plant immune system. Therefore, the effector repertoire of a given pathogen must be balanced for a successful infection. Ralstonia solanacearum is an aggressive pathogen with a large repertoire of secreted effectors. One of these effectors, RipE1, is conserved in most R. solanacearum strains sequenced to date. In this work, we found that RipE1 triggers immunity in N. benthamiana, which requires the immune regulator SGT1, but not EDS1 or NRCs. Interestingly, RipE1-triggered immunity induces the accumulation of salicylic acid (SA) and the overexpression of several genes encoding phenylalanine-ammonia lyases (PALs), suggesting that the unconventional PAL-mediated pathway is responsible for the observed SA biosynthesis. Surprisingly, RipE1 recognition also induces the expression of jasmonic acid (JA)-responsive genes and JA biosynthesis, suggesting that both SA and JA may act cooperatively in response to RipE1. We further found that RipE1 expression leads to the accumulation of glutathione in plant cells, which precedes the activation of immune responses. R. solanacearum secretes another effector, RipAY, which is known to inhibit immune responses by degrading cellular glutathione. Accordingly, RipAY inhibits RipE1-triggered immune responses. This work shows a strategy employed by R. solanacearum to counteract the perception of its effector proteins by plant immune system., The type-III secreted effector RipE1, from Ralstonia solanacearum, triggers immune responses in Arabidopsis and Nicotiana benthamiana. Such immune responses correlate with an activation of signaling mediated by salicylic acid and jasmonic acid. RipE1-triggered immunity is suppressed by another effector in R. solanacearum, RipAY, showing a bacterial strategy to counteract effector-triggered immunity.

Aims Vascular endothelial growth factor (VEGF) can promote cell division, proliferation and migration. In this study, we aimed to investigate roles of ultrasound-mediated destruction of VEGF-targeted and paclitaxel (PTX)-loaded lipid microbubbles (VTPLLM + US) in human breast cancer cells. Methods The activity of MCF-7 cells was determined by cell counting Kit-8. Flow cytometry was performed to detect the cells apoptosis and cell cycle. The expression of cell cycle-associated proteins, matrix metalloprotein-9 (MMP-9), VEGF and apoptosis-associated proteins were detected by qRT-PCR and Western blot. Results The obtained data suggested that VTPLLM + US promoted the G1 phase cell cycle arrest and suppressed the viability of MCF-7 cells. We also found that VTPLLM + US accelerated cells apoptosis. Cell cycle-associated proteins and VEGF expression were modulated by VTPLLM + US. Moreover, VTPLLM + US was found to regulate the expression levels of apoptosis-associated proteins in MCF-7 cells. Our findings suggested that VTPLLM + US suppressed the proliferation and accelerated the apoptosis of MCF-7 cells through regulating VEGF expression. Conclusions The potential effects of VTPLLM + US on apoptosis of MCF-7 cells suggest that applying VTPLLM + US might be an effective strategy in breast cancer therapies.

e20570 Background: Although the combination of PD-1/PD-L1 immune checkpoint inhibitors (ICIs) with platinum-etoposide chemotherapy (EP) is the preferred first-line treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC), the survival benefit of the addition of ICIs was still modest. Recent studies supported that combination of ICIs and anti-angiogenic agents could be a promising therapeutic strategy for normalization the immunosuppressive microenvironment and overcoming the low efficacy of ICIs. We reported the efficacy and safety of toripalimab combined with anlotinib and EP in treatment-naïve ES-SCLC. Methods: The eligible ES-SCLC patients (18-75 years, ECOG PS ≤2), with measurable target lesion (RECIST v1.1) received toripalimab (240 mg, d1) combined with etoposide (100 mg/m2, d1-3) plus carboplatin (AUC = 5, d1)/cisplatin (75 mg/m2, d1) and anlotinib (12 mg QD, d1-14) of a 21-day cycle for 4-6 cycles, then patients with CR、PR or SD could continue to receive maintenance therapy with toripalimab and anlotinib until disease progression. The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety. Results: Between 2018 October and 2020 November, 16 treatment-naïve ES-SCLC patients (14 males, 2 females) were enrolled. The median age is 63 (range, 42-74) years. The median follow-up was 7.6 months. 100% (16/16) patients achieved an objective response (1 CR and 15 PR). The DCR was also 100% (16/16). The median DOR had not been reached (range, 4.8+ to 21.9+ month). 37.5% (6/16) patients had disease progression after six months of treatment, while median PFS was not reached. As of Jan 31, 2021, all patients were still alive. The median OS had not been reached. 62.5% (10/16) patients remained on-treatment. The most common adverse events (AEs) were grade 1-2 anemia (75%), decreased appetite (50%) and neutropenia (43.8%). Seven patients had Grade 3 AEs (5 neutropenia; 1 leukopenia, 1 emesis, and 1 ketoacidosis). No Grade 4/5 AEs occurred. Conclusions: Toripalimab combined with anlotinib and etoposide plus carboplatin/cisplatin showed promising anti-tumor activity and tolerable toxicities in treatment-naïve ES-SCLC. Clinical trial information: NCT04731909.

e21635 Background: DNA damage response and repair (DDR) pathway alteration is known as a predictive biomarker of platinum-based chemotherapy sensitivity in urothelial carcinoma, breast cancer, ovarian cancer, and prostate cancer. However, the predictive value of DDR in patients with non-small cell lung cancer (NSCLC) is still uncertain. This study investigated the DDR mutations (MUT) of NSCLC to identify potential predictive biomarker. Methods: A retrospective analysis of patients with NSCLC was performed. Targeted exon sequencing with the Next Generation Sequencing (NGS) were performed for 298 patients, and they were divided into two groups based on the presence or absence of mutations in 36 DDR genes. Results: 50 patients treated with platinum-based chemotherapy were identified, of which 17 harbored alterations in DDR genes. The median age was 60.5 years (range, 43 to 79 years). A total of 50 patients were evaluated, the objective response rate (ORR) of patients with DDR MUT was 17.6%, ORR 0% for DDR wild-type (WT), and the disease control rate (DCR) was 76.4% for DDR MUT, 48.5% for DDR WT. In terms of survival analysis, patients with DDR MUT had significantly improved median progression-free survival (mPFS) of 9.2 months compared with 4.8 months for DDR WT (Hazard Ratio (HR) = 0.4134, log-rank P = 0.0117). When EGFR and ALK mutations were excluded, there was no significant difference in mPFS between DDR MUT and WT, but DDR MUT has a tendency to be higher than WT (mPFS: 8.0 vs. 4.7 months, HR = 0.5060, log-rank P = 0.1022). Nevertheless, there was no significant difference in the median overall survival (mOS) between two groups (DDR MUT vs. DDR WT: 21.7 vs. 29.4 months, HR = 1.537, log-rank P = 0.3756), even after EGFR and ALK mutations were excluded, no significant difference can also be gained (HR = 1.818, log-rank P = 0.3972). Conclusions: DDR mutations may be a positive predictive biomarker for response to platinum-based chemotherapy in patients with NSCLC.

Stress urinary incontinence is a distressing and burdensome condition affecting approximately one third of pregnant women and pelvic floor muscle training is recommended as the first-line treatment. Convenient and cost-effective regimen of pelvic floor muscle training is required to facilitate the treatment of stress urinary incontinence and improve the adherence to treatment in pregnant women.To determine the effectiveness of app-based audio guidance pelvic floor muscle training on the treatment of stress urinary incontinence in primiparas.The study was a two-arm, parallel, randomized controlled clinical trial.The study was conducted in the obstetric clinic of a tertiary maternity hospital in Hangzhou, China.A total of 108 eligible primiparas were enrolled from January to April 2018.Participants were randomly allocated (1:1) to the audio group or the control group. Primary outcomes included severity of stress urinary incontinence and adherence to pelvic floor muscle training assessed by the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form and the Broome Pelvic Muscle Self-Efficacy Scale, respectively. Secondary outcomes included pelvic floor muscle strength, bladder neck mobility and sexual function measured by vaginal palpation and pelvic floor muscle surface electromyography, perineal ultrasound and Female Sexual Function Index, respectively. Data analysis followed the intention-to-treat principle. Generalized estimation equation model, t-test and chi-square test were used to examine intervention effect on primary outcomes and secondary outcomes, respectively.Participants showed significant improvement in symptom severity across the study, which was most significant at 6 weeks postpartum (β = -4.245, p 0.001). No significant difference was found in symptom severity between groups (β = -0.344, p = 0.168). The interaction effect between intervention and time on adherence was significant. Compared with the control group, greater self-efficacy was shown in the audio group at 6 weeks (β = 4.425, p = 0.009), 3 months (β = 3.204, p 0.001) and 6 months (β = 4.457, p 0.001) postpartum. Participants in the audio group indicated less bladder neck descent (16.5 vs. 19.5, p = 0.020) at 6 weeks postpartum, better pelvic floor muscle strength (12.5% vs. 34.0%, p = 0.012; 4.2% vs. 18.0%, p = 0.030) and sexual function (22.2 vs. 17.3, p = 0.007) at 6 months postpartum.The app-based audio guidance pelvic floor muscle training was more effective and much easier to comply for treatment of stress urinary incontinence in primiparas than the conventional home-based pelvic floor muscle training.

Passive radio frequency identification (RFID) is an automatic identification technology which has been widely used in the field of the Internet of Things (IOT). In this paper, a RoF-based DAS RFID system with antenna diversity is proposed and experimentally demonstrated. The dynamic sensitivity of uplink is specially considered and photonics lantern (PL) is used to reduce the loss of signal combination. In order to verify the ability of the proposed system, we conduct a series of experiments depends on different number of tags and different transmitting power levels with the proposed system and RF switchable system in a typical lab environment. The experimental results show that the new approach improve the tag detection speed by almost 15% over a sparse environment and 10% over a dense environment respectively, compared with a RF switchable RoF DAS RFID system. The new approach is more accurate and faster than the RF switchable system with the same reader transmission power.

To evaluate the characteristics of primary hepatic carcinoma (PHC) teed by the right renal capsular artery(RRCA) and to assess the technical success rate,tumor response and complications in patients treated with transcatheter arterial chemoembolization (TACE) via the RRCA with or without other extrahepatic arteries and/or intrahepatic arteries.From July 2010 to February 2014,23 patients were treated by TACE via the RRCA. We evaluate the characteristics of tumor, the blood supply situation of RRCA and the technical success rate, complications and tumor response of TACE via the RRCA.Tumor size was 90.60+/-48.23 mm. Of the 23 rumors,3 were located in segment V, 11 in segment VI and 9 in segment VII.8 cases were found to have RRCA supply at the first TACE session. The technical success rate was 100%.No severe complication occurred in 23 patients. Among the 23 patients, CR, PR, SD and PD were achieved in 3(13.0%), 10(43.5%), 2(8.7%), 8(34.8%) respectively. The objective response rate was 56.5%. The overall cumulative 6 month, 1-3-and 5-year survival rates and the median survival time were 82.6%, 52.2%,21.7%, 17.4% and 16.8 months, respectively.RRCA can participate in tumor blood supply when it located in the right hepatic lobe and with a larger diameter, or it was small but located in the bare area.Superselective intubation of RRCA with microcatheter and precise TACE via right renal capsular artery is safe ,effective and feasible.