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Lu Zhang,1– 3,* Fei Teng,1,2,* Huajie Xin,1,2 Wei Xu,1,2 Wei Wu,4 Chenguo Yao,3 Zhiqiang Wang1,2 1Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 2Center of Thoracic Cancer, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 3The State Key Laboratory of Power Transmission Equipment and System Security and New Technology, College of Electrical Engineering, Chongqing University, Chongqing, 400044, People’s Republic of China; 4College of Biological Engineering, Chongqing University, Chongqing, 400030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lu Zhang; Zhiqiang Wang, Chongqing University Cancer Hospital, No. 181 Hanyu Road, Shapingba District, Chongqing, 400030, People’s Republic of China, Email luzhang_524@aliyun.com; zhiqiangwang@21cn.comAbstract: Patients diagnosed with glioma typically face a limited life expectancy (around 15 months on average), a bleak prognosis, and a high likelihood of recurrence. As such, glioma is recognized as a significant form of malignancy. Presently, the treatment options for glioma include traditional approaches such as surgery, chemotherapy, and radiotherapy. Regrettably, the efficacy of these treatments has been less than optimal. Nevertheless, a promising development in glioma treatment lies in the use of hydrogel nano-systems as sophisticated delivery systems. These nano-systems have demonstrated exceptional therapeutic effects in the treatment of glioma by various responsive ways, including temperature-response, pH-response, liposome-response, ROS-response, light-response, and enzyme-response. This study seeks to provide a comprehensive summary of both the therapeutic application of hydrogel nano-systems in managing glioma and the underlying immune action mechanisms. Keywords: glioma, hydrogel nano-system, immunotherapy, tumor immune microenvironment

Qingyan Kong, Mengshi Yi, Fei Teng, Hang Li, Zheyu Chen Division of Hepatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of ChinaCorrespondence: Zheyu Chen, Division of Hepatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Email kqydoctor@163.comBackground: Recent research has suggested that sarcopenia may have an impact on postoperative outcomes. The number of hepatocellular carcinoma (HCC) patients with metabolic dysfunction-associated fatty liver disease (MAFLD) has increased significantly over time. The main objective of this study was to investigate the impact of sarcopenia on the prognosis of HCC patients with MAFLD after hepatectomy.Methods: A multivariate Cox proportional hazards model and a propensity score matching (PSM) analysis were conducted to ensure that the baseline characteristics were similar. Kaplan‒Meier survival curves were used to compare the prognosis of the two groups.Results: This study involved 112 HCC patients with MAFLD undergoing hepatectomy. Sarcopenia was indicated as a risk factor for both recurrence-free survival (RFS) and overall survival (OS) in HCC patients with MAFLD after multivariate analysis (p=0.002 and 0.022, respectively). After conducting PSM analysis, Kaplan‒Meier survival curve analysis revealed significant differences in both the RFS and OS between the two groups (p=0.0002 and p=0.0047, respectively). All results showed that sarcopenia had a poor prognosis for HCC patients with MAFLD undergoing hepatectomy.Conclusion: In summary, our study suggests that sarcopenia might be a risk factor for OS and RFS in HCC patients with MAFLD who underwent hepatectomy through multivariate analysis and PSM analysis. Sarcopenia imperils postoperative survival rates and this finding can guide clinical decision-making. For postoperative patients, preventing or treating sarcopenia can potentially improve survival outcomes for patients with HCC and MAFLD.Keywords: sarcopenia, metabolic dysfunction-associated fatty liver disease, hepatocellular carcinoma, hepatectomy

Ziyi Xu,1,* Xuezhi Hao,1,* Qi Wang,2 Jing Wang,2 Ke Yang,3 Shouzheng Wang,1 Fei Teng,1 Junling Li,1 Puyuan Xing1 1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 2Department of Medical Oncology, Beijing Chaoyang Sanhuan Hospital, Beijing, 100021, People’s Republic of China; 3Department of Medical Oncology, Cancer Hospital of Huanxing, Beijing, 100021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junling Li; Puyuan Xing, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Email lijunling@cicams.ac.cn; xingpuyuan@cicams.ac.cnObjective: Osimertinib is the standard targeted strategy for lung adenocarcinoma patients harboring epidermal growth factor receptor (EGFR)-activating mutation who have achieved acquired mutation T790M beyond progression of first-line EGFR-tyrosine kinase inhibitor (TKI). In a real world setting, the efficacy for osimertinib as a subsequent treatment beyond first-generation EGFR-TKI progression under complex circumstances such as different T790M mutation status is still worth exploring.Methods: Records of 84 lung adenocarcinoma patients with an EGFR sensitive mutation who received first-generation EGFR-TKI as first-line therapy and sequenced by osimertinib after progression were retrospectively reviewed in this study. The assessment of efficacy of subsequent osimertinib treatment was evaluated by progression free survival (PFS), objective response rate (ORR), complete response (CR), partial response (PR), disease control rate (DCR) and stable disease (SD) rates. Relationship between PFS and clinicopathological characteristics was analyzed using univariate analysis.Results: Until the median follow-up time of 23.7 months (IQR 10.8– 29.0 months), the median PFS (mPFS) of subsequent osimertinib was 17.0 months (HR 1.744, 95% CI, 13.547– 20.382). Among 60 patients who had at least one measurable lesion, 35.0% of patients (21/60) had PR to osimertinib, and 63.3% patients (38/60) had SD during osimertinib treatment. The ORR was 35.0%, and the DCR was 98.3%. Patients with acquired T790M mutation which was detected by NGS or ddPCR assay had an mPFS of 17.0 months (HR = 1.032, 95% CI, 14.941– 18.987), while the remaining 17 patients who had negative or unknown T790M mutation status had an mPFS of 23.5 months (HR = 9.404, 95% CI, 5.068– 41.932). No significant difference was observed in those with and without T790M mutation (P = 0.704).Conclusion: Osimertinib may serve as an alternative subsequent choice after progression of first-generation EGFR-TKI in EGFR-mutated lung adenocarcinoma and may represent a potential treatment option for selected T790M-negative patients.Keywords: osimertinib, progression, subsequent therapy, lung adenocarcinoma, T790M mutation

Yanfang Zhang,1,* Dan Li,1,* Qi Yan,1 Xueru Song,1 Wenyan Tian,1 Yingmei Wang,1 Fei Teng,1 Likun Wei,1 Jinghua Wang,2 Huiying Zhang,1 Fengxia Xue1 1Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China; Tianjin Key laboratory of Female Reproductive Health and Eugenics, Tianjin, People’s Republic of China; 2Laboratory of Epidemiology, Tianjin Neurological Institute, Department of Neurology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huiying Zhang; Fengxia XueDepartment of Obstetrics and Gynecology, Tianjin Medical University General Hospital, 154 Anshan Road, He Ping District, Tianjin, 300052, People’s Republic of ChinaTel +86-22-60363762Fax +86-22-60362636Email huiying_zhang2020@126.com, xuefengxia@tmu.edu.cnPurpose: To evaluate the effects of body weight loss on reproductive outcomes in young women with early-stage endometrial cancer (EC) and atypical hyperplasia (AH) who underwent fertility-sparing therapy.Patients and Methods: Patients with well-differentiated EC (n=8, FIGO stage Ia) and AH (n=36) who achieved complete regression after fertility-sparing therapy were retrospectively reviewed. Patients were divided into a weight loss group (n=25) and a non-weight loss group (n=19). Subgroup analysis according to body mass index and relative weight loss were performed to investigate the effect of weight loss on pregnancy and live birth outcomes. Univariate and multivariate logistic regression analyses were undertaken to determine pregnancy-associated factors.Results: Mean body weight and body mass index at pre-progestin treatment and at fertility treatment initiation were 70.63± 12.03 and 67.08± 8.18 kg, respectively, 27.06± 4.44 and 25.73± 3.15 kg/m2, respectively. Twenty-five patients (56.82%) lost weight, the median absolute weight loss was 5.00 kg (1.00– 34.50), and the median relative weight loss was 6.70% (1.00– 36.00%) over a median of 12 months (5.00– 97.00). A favorable pregnancy rate (65.91%) and live birth rate (50.00%) were achieved. The pregnancy and live birth rates were meaningfully higher in the weight loss group than in the non-weight loss group (88.00% vs 36.84%, P=0.000; 64.00% vs 31.58%, P=0.033); weight loss ≥ 5% significantly increased pregnancy and live birth rate in patients with BMI ≥ 25 kg/m2. The risk ratio of weight loss ≥ 5% in multivariate logistic analysis for pregnancy was 10.448 (1.102, 99.056, P=0.041).Conclusion: Weight loss could positively affect pregnancy rate and improve live birth rate in overweight and obese women with early-stage EC and AH during/after fertility-sparing therapy. Weight loss ≥ 5% increased pregnancy and livebirth rates significantly in overweight and obese women.Keywords: weight loss, reproductive outcomes, fertility-sparing therapy, endometrial cancer, atypical hyperplasia

Xin Wang,1,2 Feifei Teng,2 Jie Lu,3 Dianbin Mu,4 Jianbo Zhang,4 Jinming Yu1,21Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, People’s Republic of China; 3Department of Neurosurgery, Shandong Province Qianfoshan Hospital of Shandong University, Jinan, Shandong 250014, People’s Republic of China; 4Department of Pathology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong 250117, People’s Republic of ChinaBackground: The inhibitors of nuclear factor kappa-B kinase subunit epsilon (IKBKE) and TANK-binding kinase 1 (TBK1) are important members of the nonclassical IKK family that share the kinase domain. They are important oncogenes for activation of several signaling pathways in several tumors. This study aims to explore the expression of IKBKE and TBK1 and their prognostic role in stage I non-small cell lung cancer (NSCLC).Patients and methods: A total of 142 surgically resected stage I NSCLC patients were enrolled and immunohistochemistry of IKBKE and TBK1 was performed.Results: IKBKE and TBK1 were expressed in 121 (85.2%) and 114 (80.3%) of stage I NSCLC patients respectively. IKBKE expression was significantly associated with TBK1 expression (P=0.004). Furthermore, multivariate regression analyses showed there was a significant relationship between patients with risk factors, the recurrence pattern of metastasis and IKBKE+/TBK1+ co-expression (P=0.032 and P=0.022, respectively). In Kaplan–Meier survival curve analyses, the IKBKE+/TBK1+ co-expression subgroup was significantly associated with poor overall survival (P=0.014).Conclusions: This is the first study to investigate the relationship between IKBKE and TBK1 expression and clinicopathologic characteristics in stage I NSCLC patients. IKBKE+/TBK1+ co-expression was significantly obvious in patients with risk factors and with recurrence pattern of distant metastasis. Furthermore, IKBKE+/TBK1+ is also an effective prognostic predictor for poor overall survival.Keywords: IKBKE, TBK1, NSCLC, prognosis, cancer

Perinatal factors can shape fecal microbiome patterns among pregnant women and their infants. However, there is scarce information about the effect of maternal demographics and perinatal exposures on antibiotic resistance genes (ARG) and mobile genetic element (MGE) patterns in pregnant women and infants. We examined fecal samples from pregnant women during their third trimester of pregnancy (n = 51) and 6-month-old infants (n = 40). Of the 91 participants, 72 represented 36 maternal-infant dyads, 15 were additional pregnant women, and 4 were additional infants. We assessed the effects of demographics, pre-pregnancy BMI, smoking and parity in the pregnancy resistome and the effects of demographics, delivery mode, feeding habits and prenatal antibiotic treatment on the infancy resistome. ARG and MGE richness and abundance were assessed using a SmartChip qPCR-array. Alpha diversity (Shannon and Inverse Simpson index) and beta diversity (Sorensen and Bray-Curtis index) were calculated. The Wilcoxon and the Kruskal non-parametric test were used for comparisons. There is a high variability in shared resistome patterns between pregnant women and their infants. An average of 29% of ARG and 24% of MGE were shared within dyads. Infants had significantly greater abundance and higher diversity of ARG and MGE compared to pregnant women. Pregnancy and infancy samples differed in ARG and MGE gene composition and structure. Composition of the fecal resistome was significantly associated with race in pregnant women, with non-white women having different patterns than white women, and, in infants, with extent of solid food consumption. Our data showed that the pregnancy and infancy resistome had different structure and composition patterns, with maternal race and infant solid food consumption as possible contributors to ARG. By characterizing resistome patterns, our results can inform the mechanism of antibiotic resistome development in pregnant women and their infants.

An explosion on the ground surface can cause considerable damage to underground structures. In this study, a series of experimental and numerical investigations were conducted to examine the performance and reinforcing mechanism of reinforced soil subjected to blast loads. An excavated pit backfilled with sand only (unreinforced soil) and sand reinforced with three layers of geotextiles (reinforced soil) were used as test models in a field explosion test. In the field explosion test, blast pressures in air and soil, ground deformation, and mobilized reinforcement tensile strain were measured. The test results obtained for the reinforced and unreinforced soil were compared to evaluate the effectiveness of using soil reinforcement as a protective barrier against blast loads. The test results indicated that peak blast pressure in the reinforced soil was only 10–28% of those in the unreinforced soil. Two reinforcing mechanisms were identified in this study: the tensioned membrane effect and lateral restraint effect. Moreover, a series of numerical analyses were performed to evaluate the effects of reinforcement parameters on the blast pressure. This study provides useful insights into the application and design of soil reinforcement as an alternative antiexplosion measure to protect underground structures against surface explosions. [ABSTRACT FROM AUTHOR]

Concurrent chemoradiation therapy (CRT) followed by durvalumab had demonstrated significant survival benefit for unresectable stage III (USIII) non-small cell lung cancer (NSCLC) patients (pts) in PACIFIC trial. However, 20%-30% pts have no chance to receive immunotherapy due to disease progression (PD) or intolerable toxicity during CRT period. This prospective study aimed to evaluate safety and efficacy of concurrent durvalumab with CRT followed by durvalumab in USIII NSCLC. CRUISER is a multi-center phase 2 study with USIII NSCLC. All pts will receive concurrent durvalumab and CRT followed by durvalumab until PD or unacceptable toxicity. Optional induction therapy with one cycle is allowed upon investigators' decisions. The primary endpoint was the incidence of ≥3 grade immune-mediated adverse event (imAE). Second endpoints were progression free survival (PFS) according to RECIST 1.1, overall survival (OS), and objective response rate (ORR). Between Jan 2021 and Sep 2022, 35 pts from 4 hospitals were enrolled. Median age was 64 years, 85.7% were male, and 54.3% were squamous carcinoma. IIIA/ /IIIB /IIIC NSCLC accounted for 34.3% (12/35), 48.6% (17/35), and 17.1% (6/35), with most of them (91.4%, 32/35) having N2/N3 metastases. Among the 20 (57.1%) pts received induction therapy, 17 pts received durvalumab plus chemotherapy. The median total dose of radiotherapy was 60 Gy. As of December 8th, 2023, Grade ≥3 imAE occurred in 4(11.4%) of 35 pts. With median follow-up of 19.0 months (m), median PFS was 14.4m (95% CI 10.2, NE), and one-year PFS rate was 60.9%. A trend of better one-year PFS rate was observed in subsets with induction therapy than without (68.8% vs 50.5%), received ＞ one cycle concurrent chemoradiation than one cycle (64.3% vs 51.8%) and received durvalumab with ≥seven cycles than ＜seven cycles (82.3% vs 33.1%). Median OS was not reached, and one-year OS rate was 76.4%. ORR was 80% (20/25) in evaluable set. Concurrent durvalumab with CRT followed by durvalumab for USIII NSCLC is tolerable. Radiotherapy with induction therapy and more cycles of concurrent chemoradiation and durvalumab demonstrates better outcome via this treatment regimen. [ABSTRACT FROM AUTHOR]