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This study was to explore the efficacy and safety of camrelizumab combined with apatinib in patients with advanced liver cancer. Moreover, the relationship between peripheral blood parameters and tumor response rate was also investigated. Patients with unresectable or recurrent primary liver cancer (PLC) who received treatment from July 2019 to July 2020 in the First Affiliated Hospital of Guangxi Medical University were included in this single-center retrospective study. The patients were treated with camrelizumab (200 mg, intravenous q2w) plus apatinib (250 mg, oral qd) until the occurrence of disease progression or unbearable toxicity. All the patients underwent blood routine test and detection of lactate dehydrogenase and serum albumin levels before treatment. The primary endpoints were objective response rate (ORR) and disease control rate (DCR). This study included a total of 45 patients. The overall ORR was 33.3% [95% confidence interval (CI),19.0-47.7] and the overall DCR was 57.8% (95% CI, 42.8-72.8). The ORR and DCR were higher in the first-line treatment than those in the second-line treatment (ORR: 45.5% vs. 21.7%, DCR: 63.6% vs. 52.3%). Median progression-free survival in the second-line treatment was 10.5 months (95% CI, 7.9-13.1, P = 0.022). Adverse events occurred in 39 (86.7%) patients. Grade 3/4 adverse reactions occurred in 7 (15.6%) patients. One patient (4.3%) was terminated from treatment due to adverse events. One patient (4.3%) died, which was potentially associated with adverse events. Subgroup analysis indicated that the remission rate in patients with high lymphocyte to monocyte ratio (H-LMR) was higher than that in patients with low lymphocyte to monocyte ratio (L-LMR) (56.25% vs. 25.93%, P = 0.047), and the remission rate in patients with high Prognostic Nutritional Index (H-PNI) was higher than that in patients with low Prognostic Nutritional Index (L-PNI) (66.7% vs. 26.5%, P = 0.046). Camrelizumab combined with apatinib in the treatment of PLC showed encouraging clinical efficacy, with tolerable toxicities. Levels of PNI and LMR may serve as predictors of the prognosis of advanced PLC patients who receive immunotherapy combined with targeted therapy.

BackgroundAt present, chemotherapy is still the primary treatment for advanced biliary tract carcinoma, but it is challenging to balance the efficacy and side effects. Network meta-analysis (NMA) is a better way to identify the protocol, and the advantage is that it can be combined with direct and indirect evidence to judge the best treatment regimens. Therefore, we conducted NMA on the searched randomized controlled trials (RCTs).MethodsNMA was conducted regarding the searched RCTs by comparing progression-free survival (PFS), overall survival (OS), objective remission rates (ORRs), and adverse events (AEs) of different chemotherapy protocols.ResultsWe screened 24 studies that met the inclusion criteria for further analysis. Compared with other regimens, the best supportive care (BSC) or FUFA protocol has a worse OS. Folfox4, GEMOX+erlotinib, and C+GEMOX can improve patients’ PFS compared with BSC. Patients receiving GP+cediranib protocol have higher ORRs. There was reduced neutropenia grade ≥3 when adopting GP+cediranib, GS, C+GEMOX, RAM+GP, and MER+GP than when using FUFA protocol. The probability of vomiting of XELOX is lower than that of GEM+XELOX. There is a lower diarrhea incidence of XELOX than that of GEMOX+erlotinib. The results of cluster grade analysis illustrated that GEMOX+erlotinib owned a higher ORR and a higher surface under the cumulative ranking (SUCRA) of neutropenia and vomiting but also had a lower SUCRA of diarrhea and fatigue. Meanwhile, both GEMOX and C+GEMOX have a better ORR and a higher AE SUCRA.ConclusionThe NMA demonstrated that chemotherapy combined with targeted therapy has better efficacy and lower incidence of AEs than chemotherapy alone.

Objective: The goal of our current study is to assess the immunohistochemical of p53, p21, nm23, and VEGF expression in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) prognosis after hepatectomy, as well as the prospective molecular mechanisms of prognostic indicator. Methods: There were 419 HBV-related HCC patients who were from southern China of Guangxi province and were used to evaluate the immunohistochemical expression for these biomarkers in prognosis. A genome-wide expression microarray dataset of HBV-related HCC were obtained from GSE14520. Results: In our study, the expression of p53, p21, and nm23 in cancer tissues of patients with hepatitis B-related hepatocellular carcinoma did not affected the clinical outcome of 2 years, 5 years or overall. Patients with high expression of VEGF had a worse overall survival after 2 years of surgery than patients with low expression (adjusted P=0.040, adjusted HR = 1.652, 95% CI = 1.024-2.665). Survival analysis of VEGF in GSE14520 cohort also demonstrated that VEGF mRNA expression also significantly associated with HBV-related HCC OS (adjusted P=0.035, adjusted HR =1.651, 95% CI =1.035-2.634). The prospective molecular mechanisms by co-expression analysis suggested that VEGF might be correlated to regulation of cell proliferation, cell growth and apoptotic process, Rap1 signaling pathway, HIF-1 signaling pathway, PPAR signaling pathway, cell cycle. Whereas the GSEA suggested that VEGF might involve in the regulation of HIF and HIF1A pathway, and TP53 regulation pathway. Conclusion: Our findings suggested that VEGF might be a prognostic indicator of HBV-related HCC, and we also identified the VEGF prospective molecular mechanisms through the whole genome co-expression and GSEA approaches.

Jian Xi,1– 3,* Zhiming Zeng,1,2,* Xin Li,1,2 Xin Zhang,1,2 Jing Xu1,2 1Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan Province, 410008, People’s Republic of China; 2Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, 410008, Hunan, People’s Republic of China; 3Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan Province, 410008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing XuDepartment of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan Province, 410008, People’s Republic of ChinaEmail xujing1981@csu.edu.cnObjective: To detect the expression level of tRNA-derived fragments secreted by extracellular vesicles in hypopharyngeal cancer and explore the influence of tRNA-derived fragments on the occurrence of hypopharyngeal cancer and lung metastasis.Methods: After high-speed centrifugation, tRNA, which was extracted from the extracellular vesicles of patients with hypopharyngeal cancer and healthy subjects, was sequenced using microarrays. The expression of three differentially expressed tRNAs in hypopharyngeal cancer, healthy subjects, human normal laryngeal epithelial cells and hypopharyngeal cancer line was detected by qRT-PCR. The correlation between the upregulated tRNA, as identified by qRT-PCR, and the clinicopathological features of the non-lung metastatic patients was further analyzed. Finally, the expressions of upregulated tRNA were compared between the non-lung metastatic and lung metastatic patients. The risk factors of hypopharyngeal cancer with lung metastatic were identified by the Cox regression analysis.Results: By high-speed centrifugation, extracellular vesicles were extracted successfully. It was found that a variety of tRNAs in the extracellular vesicles from patients with hypopharyngeal cancer by sequencing. qRT-PCR validation indicated that tRF-1:30-Lys-CTT-1-M2 was significantly overexpressed in hypopharyngeal cancer patients and tumor cells, especially in lung metastatic patients. It was indicated that tRF-1:30-Lys-CTT-1-M2 overexpression was closely related to such pathological features as tumor staging, differentiation grade, smoking history and drinking history. According to the Cox regression analysis, stage III–IV, smoking history, drinking history and tRF-1:30-Lys-CTT-1-M2 overexpression were independent risk factors for metastasis of hypopharyngeal cancer.Conclusion: tRF-1:30-Lys-CTT-1-M2 was overexpressed in patients with hypopharyngeal cancer and was identified as an independent risk factor for lung metastasis. It can be used as a novel biomarker for the diagnosis and lung metastasis monitoring of hypopharyngeal cancer.Keywords: extracellular vesicles, tRNA-derived fragment, hypopharyngeal cancer, lung metastasis, cancer marker

Background Composite lymphomas (CLs) are a kind of rare disease that two distinct categories of lymphomas occur in the same patient. Histologically, composite lymphomas can be composed of a Hodgkin’s lymphoma and a non-Hodgkin lymphoma or two distinct non-Hodgkin lymphomas. So far, most of the cases have been reported to occur in a single anatomical site or mass. Case presentation: A 61-year-old man without any B-type symptoms complained of an enlarging mass in the abdomen for one month. A 10 × 10 cm abdominal mass could be touched in the hypogastric region. Through pathological biopsy, mantle cell lymphoma can be diagnosed. After one cycle chemotherapy regimen of FCD, red rashes and blisters came out on the patient's right lower extremity. Cutaneous diffuse large B-cell lymphoma (DLBCL) was diagnosed by skin biopsy. In this report, we describe a case of composite lymphoma occurring in different organs, which consisted of primary mantle cell lymphoma (MCL) and cutaneous DLBCL, leg type. The patient then received a series of chemotherapy regimens without rituximab then achieved partial response (PR). Conclusions To our knowledge, this is a rare case of CLs occurring in different anatomic sites that were treated by chemotherapy and achieved PR. As we learn more about the mechanisms and treatment of CLs, we look forward to more treatment options in the future for patients to give them a better prognosis.

With the rapid explosion of data volume from mobile networks, edge caching has received significant attentions as an efficient approach to boost content delivery efficiency by bringing contents near users. In this article, cache-enabled heterogeneous networks (HetNets) considering the limited backhaul are analyzed with the aid of the stochastic geometry approach. A hybrid caching policy, in which the most popular contents are cached in the macro BSs tier with the deterministic caching strategy and the less popular contents are cached in the helpers tier with the probabilistic caching strategy, is proposed. Correspondingly, the content-centric association strategy is designed based on the comprehensive state of the access link, the cache and the backhaul link. Under the hybrid caching policy, new analytical results for successful content delivery probability, average successful delivery rate and energy efficiency are derived in the general scenario, the interference-limited scenario and the mean load scenario. The simulation results show that the proposed caching policy outperforms the most popular caching policy in HetNets with the limited backhaul. The performance gain is dramatically improved when the content popularity is less skewed, the cache capacity is sufficient and the helper density is relatively large. Furthermore, it is confirmed that there exists an optimal helper density to maximize the energy efficiency of the cache-enabled HetNets.

Intrahepatic cholangiocarcinoma (ICC) arises from the biliary epithelium and is a relatively rare and highly fatal neoplasm. The prognosis is poor, and survival is limited to a few months. Here, we report a case of advanced ICC that was successfully treated with apatinib, a new oral tyrosine kinase inhibitor that targets the intracellular domain of vascular endothelial growth factor receptor-2. To the best of our knowledge, this is the first case report of the successful use of apatinib for advanced ICC; this treatment has demonstrated fewer toxic effects than traditional cytotoxic chemotherapy. The progression-free survival time was 8 months. The only toxicity observed was mild hand-foot syndrome. Therefore, apatinib may be an additional option for the treatment of advanced ICC, but further prospective studies are needed to optimize the treatment.

e16132 Background: A variety of staged hepatic resection has been applied in patients (pts) with hepatocellular carcinoma (HCC) who had an inadequate future-remnant-liver (FRL), but the clinical outcomes remain unsatisfactory. Based on the clinical data of apatinib (a highly selective VEGFR-2 inhibitor) and camrelizimab (anti‐PD‐1 antibody) in HCC pts, we therefore evaluated the safety and efficacy of portal vein ligation (PVL) in combination with apatinib plus camrelizimab for primary HCC with insufficient residual liver volume. Methods: Pts aged 18-75, with HCC, Child-Pugh A status, BCLC stage A-C, preoperative indocyanine green retention rate at 15 min < 10%, and preoperative FLR/standardized liver volume (SLV) < 30% (for pts without cirrhosis ) and < 40% (for pts with cirrhosis ) were enrolled. Pts received PVL followed by camrelizimab (200mg, iv, d1 q2w) plus apatinib (250mg, po, pd, q2w) until surgical criteria were met. Pts underwent second-stage hepatic resection 4 weeks after treatment discontinuation, and continued treatment with apatinib plus camrelizimab for 1 year or endpoints occurred. The primary endpoints were resection rate of conversion surgery and ORR (objective response rate). Results: Between Apr 21, 2020 to Jan 20, 2021, 14 pts were enrolled in this trial. The estimated median preoperative FLR/SLV for all pts was 34.6%. Among the 10 evaluable pts, 7 met the criteria for surgery and 5 completed second-stage hepatectomy except for 2 pt who refused and waited for surgery, respectively. The median interval time of the two stages of surgery was 138.8 days. ORR was 40%, and disease control rate (DCR) was 100% (4 pts with partial response and 6 pts with stable disease). The other 4 pts are waiting for the evaluation. No adverse events (AEs) of grade 3 or worse occurred after PVL. The most common treatment-related AEs in pts during treatment with apatinib plus camrelizimab included hypoalbuminemia (36%), increased aspartate aminotransferase (AST) (100%) and rash (29%). Major AEs in pts underoing second-stage hepatectomy were pneumonia (100%), increased AST (100%), increased alanine transaminase (100%) and anemia (100%). One patient died of postoperative pulmonary infection. Conclusions: PVL in combination with apatinib plus camrelizimab followed by staged resection may be a safe and effective treatment option for HCC pts with insufficient FLR. Clinical trial information: ChiCTR2000033692.

314 Background: Hepatocellular carcinoma (HCC) is particularly prevalent in China because of the high prevalence of chronic hepatitis B infection. In the last decade, sorafenib was the first molecular target drug approved for the treatment of advanced liver cancer. Until recently, the combination of angiogenic inhibitor with anti-PD-1 /L1 monoclonal antibody has represented significant efficacy over sorafenib monotherapy in the first-line regimen of unresectable HCC. Nevertheless, there are still unmet needs in clinical practice due to limited choice of drugs. Anlotinib is a novel oral multi-targeted tyrosine kinase inhibitor that targets VEGF receptors 1/2/3, FGF receptors 1-4, PDGF receptors α and β, and c-kit, and has been approved for standard treatment of non-small cell lung cancer, small cell lung cancer and soft tissue sarcoma in China. Toripalimab, a humanized IgG4 mAb against PD-1, is the first Chinese-produced PD-1 inhibitor marketed, which has been approved as a second-line treatment for metastasis melanoma. This study aims to evaluate the efficacy and safety of anlotinib plus toripalimab as the first-line treatment for unresectable HCC. Methods: This was a single-arm, multicenter, phase II trial. 30 patients with unresectable HCC, Child-Pugh ≤7 and ECOG PS

Manufacturing industry plays an important role in the national economy. However, it is worth noting that scientific and technological innovation in manufacturing industry is accompanied by risks. One of the important ways to solve technological risks is science and technology insurance. In this paper, we first analyse the development status of science and technology insurance in China, and then establish an index evaluation system by using the analytic hierarchy process (AHP) and the fuzzy comprehensive evaluation method. The index evaluation system includes three layers and selects 24 indicators, which can help the insurance companies to scientifically and quantitatively evaluate high-tech manufacturing companies. It also can avoid subjective and difficult-to-quantify problems in the past evaluation process. Finally, an empirical study is showed to explain how to quantify these indicators and how to calculate the weight coefficient values for each indicator. Our findings can provide relevant countermeasures and suggestions for insurance companies, high-tech manufacturing companies, and governments.

Zhi-ming Zeng,1 Fei-fei Luo,2 Lin-xia Zou,3 Rong-quan He,1 Deng-hua Pan,2 Xin Chen,2 Ting-ting Xie,2 Yuan-qing Li,2 Zhi-gang Peng,1 Gang Chen2 1Department of Medical Oncology, 2Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, 3Department of Children Rehabilitation Medicine, Guangxi Maternal and Child Health Hospital, Nanning, China Background: Human papillomaviruses (HPVs) are causally associated with the tumorigenesis of several classes of cancers. However, the prevalence of HPV in gastric cancer (GC) has not yet been systematically reviewed. Hence, a meta-analysis was conducted to estimate the HPV prevalence in patients with GC, and its potential etiologic significance was assessed. Methods: The pooled HPV prevalence and 95% confidence intervals (CIs) were estimated among all GC patients. Heterogeneity was described by using the I2 statistic. Sources of heterogeneity were explored by meta-regression and stratified analyses. The meta-influence was applied to evaluate the influence of a single study on the pooled estimates. Odds ratios (ORs) and 95% CIs were computed for case–control studies. For research providing clinicopathological parameters of age, sex, pathological, differentiated, and clinical stages, and HPV subtypes, the corresponding pooled ORs and 95% CIs were also calculated. Results: Thirty studies were included in the current meta-analysis, involving 1,917 patients with GC and 576 controls. The pooled HPV prevalence was 28.0% (95% CI: 23.2%, 32.7%) among all the patients with GC, and the I2 was 96.9% (P

Background: For advanced or metastatic lung cancer patients (pts) in the absence of actionable genetic alterations, whose disease progressed after chemotherapy, the effective treatment options are limited. Recently, PD-1/PD-L1 inhibitors have demonstrated improved survival in advanced lung cancer. However, sufficient evidence is still lacking in Chinese lung cancer pts. Methods: Twenty lung cancer pts including 12 adenocarcinomas and 5 squamous cell carcinomas who received anti-PD-1/PD-L1 treatments as first- to fourth-line therapy were retrospectively reviewed. The majority of the pts were stage IV (17 pts). PD-L1 expression was analyzed by immunohistochemical staining. Genomic alterations were detected by using a next-generation sequencing (NGS) assay targeting 450 cancer genes. Tumor mutational burden (TMB) and microsatellite instability (MSI) status were acquired by NGS algorithm. Results: The median age of the 20 pts was 57 years (range: 36-69) and male vs. female was 3. The median time from date of diagnosis to the date of the first anti-PD-1/PD-L1 treatment was 9.5 months (range: 1-69 months). The overall response rate was 89%, including 8 partial response (PR), 9 stable disease (SD) and 2 progressive disease (PD), and the median PFS (mPFS) was not reached (NR) (range: 0.5-NR). Seven pts had one or more targetable oncogenic mutations including EGFR L858R (2) and amplification, PIK3CA (1), BRAF, ERBB2, PTEN, and ROS1 fusion. The median TMB value of the 20 pts was 11 muts/Mb (range: 2.4-38 muts/Mb). 45% of the pts had TMB greater than 20 muts/Mb, and 60% had TMB greater than 10 muts/Mb. Among the 9 pts who had the TMB greater than 20 muts/Mb, 5 pts achieved PR, 4 achieved SD, mPFS was not reached. Also, 5 pts including 2 PR and 3 SD were identified as MSI-high. In the PD-L1 positive subgroup (N=11), 5 pts achieved PR, 5 achieved SD and 1 had a PD. Furthermore, we found 5 pts with NFE2L2 mutations including 2 adenocarcinomas and 3 squamous cell carcinomas, associated with high TMB values (>20 muts/Mb) and PD-L1 positivity; all 5 pts had response to anti-PD-1/PD-L1 treatment, which include 3 PR and 2 SD with mPFS not reached (range: 6-NR). Conclusion: Our preliminary results based on a small number of pts showed a significant association between high TMB values and response of immune checkpoint inhibitors in Chinese lung cancer pts, and a strong correlation between high TMB values and high PD-L1 expression. We also reported that NFE2L2 mutation was tightly associated with high TMB value (P=0.011) and PD-L1 positivity (P=0.038), which may serve as a new predictive biomarker for advanced or metastatic lung cancer pts receiving anti-PD-1/PD-L1 treatments. Further larger cohort study is warranted. Citation Format: Jing Hu, Bixun Li, Bing Zou, Senming Wang, Ye Qiu, Maolin Yan, Zhiming Zeng, Han Yang, Yan Guan, Lei Zhang, Wei Chen, Yuan Zhang, Lei Mei, Xiaowei Dong, Ming Yao, Kai Wang. Associations of genomic alteration, tumor mutational burden with PD-L1 expression and response to immune checkpoint inhibitors in Chinese lung patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 620.

Background Hepatitis B virus (HBV) infection is a major risk factor which can lead to development of hepatocellular carcinoma (HCC). In this study, we aimed to explore the effects of toll-like receptor 4 (TLR4) downregulation on the growth and survival of HBV-related HCC cells and to examine the molecular mechanisms been involved. Methods The expression levels of TLR4 were examined in a panel of HCC cell lines (HepG2, SMMC7721, Huh7, HepG2.2.15 and Hep3B). The effects of TLR4 downregulation on the proliferation, apoptosis, and tumorigenicity of HBV-related HepG2.2.15 cells were determined. The effects of TLR4 downregulation on multiple signaling pathways were also measured. Co-immunoprecipitation and immunofluoresence staining assays were performed to investigate the interaction between TLR4 and HBV X protein (HBx). Results The mRNA and protein levels of TLR4 were significantly increased in HepG2.2.15 cells than those in the other cells which have been studied. Downregulation of TLR4 significantly decreased the proliferation and induced G2/M cell cycle arrest and apoptosis in HepG2.2.15 cells. TLR4 depletion inhibited HepG2.2.15 cell colony formation and tumor growth in nude mice. TLR4 silencing decreased the phosphorylation of ERK1/2 but not JNK1/2, p38, or NF-κB. Chemical inhibition of ERK1/2 approximately phenocopied the growth-suppressive effect of TLR4 downregulation on HepG2.2.15 cells. In addition, TLR4 showed a physical interaction with HBx. Conclusions Taken together, TLR4 plays a tumor-promoting role in HBV-related HCC cells, which is associated with regulation of ERK1/2 activation and interaction with HBx. Therefore, TLR4 may be a potential therapeutic target for HBV-related HCC.

In the Long Term Evolution system, Discontinuous Transmission and Reception (DRX/DTX) has been introduced to extend the terminal battery lifetime. In this paper, we research the power-saving provided by our proposed mechanism and the impact on the system performance under the dynamic scheduling joint the delivery of unicast and E-MBMS services. The simulation results show that this mechanism can increase the user throughput and energy efficiency, as well as maintain fairness among users..

Disseminating spatial data and delivering GIS functionality via Internet has become common-place. However, building a popular online mapping services system that serving staggering amount of Internet users remains as a challenge. This paper describes the Internet mapping architecture based on cluster technology enhanced by mapping-oriented load balancing algorithm.