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Yao Wang,1,* Mingtang Zeng,1,* Tianfei Fan,1 Ming Jia,2 Ruxi Yin,1 Jia Xue,1 Longjun Xian,3 Ping Fan,1 Mei Zhan1 1Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Nanchong Institute for Food and Drug Control, Nanchong, People’s Republic of China; 3Department of Thoracic Surgery, Institute of Thoracic Oncology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ping Fan; Mei Zhan, Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Email m13980602288@163.com; mandyzhanmei@163.comAbstract: Metal-organic frameworks (MOFs) are porous materials resulting from the coordination of metal clusters or ions with organic ligands, merging macromolecular and coordination chemistry features. Among these, zeolitic imidazolate framework-8 (ZIF-8) stands out as a widely utilized MOF known for its robust stability in aqueous environments owing to the robust interaction between its constituent zinc ions (Zn2+) and 2-methylimidazole (2-MIM). ZIF-8 readily decomposes under acidic conditions, serving as a promising candidate for pH-responsive drug delivery systems. Moreover, biomimetic materials typically possess good biocompatibility, reducing immune reactions. By mimicking natural structures or surface features within the body, they enhance the targeting of nanoparticles, prolong their circulation time, and increase their bioavailability in vivo. This review explores the latest advancements in biomimetic ZIF-8 nanoparticles for drug delivery, elucidating the primary obstacles and future prospects in utilizing ZIF-8 for drug delivery applications.Keywords: MOF, ZIF-8, cell membrane, biomimetic drug delivery

Shuli Tang,1,* Tiantian Fan,2,* Xinxin Wang,2 Can Yu,2 Chunhui Zhang,1 Yang Zhou2 1Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150010, People’s Republic of China; 2Department of Radiology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150010, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang Zhou, Department of Radiology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150010, People’s Republic of China, Tel +86-451-85718915, Email zhouyang094@126.comPurpose: With the rapid development of immunotherapy, cancer treatment has entered a new phase. Medical imaging, as a primary diagnostic method, is closely related to cancer immunotherapy. However, until now, there has been no systematic bibliometric analysis of the state of this field. Therefore, the main purpose of this article is to clarify the past research trajectory, summarize current research hotspots, reveal dynamic scientific developments, and explore future research directions.Patients and Methods: A comprehensive search was conducted on the Web of Science Core Collection (WoSCC) database to identify publications related to immunotherapy specifically for the medical imaging of carcinoma. The search spanned the period from the year 2003 to 2023. Several analytical tools were employed. These included CiteSpace (6.2.4), and the Microsoft Office Excel (2016).Results: By searching the database, a total of 704 English articles published between 2003 and 2023 were obtained. We have observed a rapid increase in the number of publications since 2018. The two most active countries are the United States (n=265) and China (n=170). Pittock, Sean J and Abu-sbeih, Hamzah are very concerned about the relationship between cancer immunotherapy and medical images and have published more academic papers (n = 5; n = 4). Among the top 10 co-cited authors, Topalian Sl (n=43) cited ranked first, followed by Graus F (n=40) cited. According to clustering, timeline, and burst word analysis, the results show that the current research focus is on “MRI”, “deep learning”, “tumor microenvironment” and so on.Conclusion: Medical imaging and cancer immunotherapy are hot topics. The United States is the country with the most publications and the greatest influence in this field, followed by China. “MRI”, “PET/PET-CT”, “deep learning”, “immune-related adverse events” and “tumor microenvironment” are currently hot research topics and potential targets.Keywords: bibliometric analysis, cancer, immunotherapy, medical imaging, CiteSpace

Teng Fan,1– 3,* Yuanyuan Huang,1– 3,* Zeyu Liu,1,2,* Jinsheng Huang,1,2 Bin Ke,1– 3 Yuming Rong,1,2 Huijuan Qiu,1,2 Bei Zhang1– 3 1TCM&VIP Department, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 3Integrated Traditional Chinese and Western Medicine Research Center, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bei Zhang, TCM&VIP Department, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People’s Republic of China, Tel/Fax +86-20-87342708, Email zhangbei@sysucc.org.cnBackground: The ChaiShao Shugan Formula (CSSGF) is a traditional Chinese medicine formula with recently identified therapeutic value in triple-negative breast cancer (TNBC). This study aimed to elucidate the underlying mechanism of CSSGF in TNBC treatment.Methods: TNBC targets were analyzed using R and data were from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The major ingredients and related protein targets of CSSGF were explored via the Traditional Chinese Medicine Systems Pharmacology database, and an ingredient–target network was constructed via Cytoscape to identify hub genes. The STRING database was used to construct the PPI network. GO and KEGG enrichment analyses were performed via R to obtain the main targets. The online tool Kaplan‒Meier plotter was used to identify the prognostic genes. Molecular docking was applied to the core target genes and active ingredients. MDA-MB-231 and MCF-7 cell lines were used to verify the efficacy of the various drugs.Results: A total of 4562 genes were screened as TNBC target genes. The PPI network consisted of 89 nodes and 845 edges. Our study indicated that quercetin, beta-sitosterol, luteolin and catechin might be the core ingredients of CSSGF, and EGFR and c-Myc might be the latent therapeutic targets of CSSGF in the treatment of TNBC. GO and KEGG analyses indicated that the anticancer effect of CSSGF on TNBC was mainly associated with DNA binding, transcription factor binding, and other biological processes. The related signaling pathways mainly involved the TNF-a, IL-17, and apoptosis pathways. The molecular docking data indicated that quercetin, beta-sitosterol, luteolin, and catechin had high affinity for EGFR, JUN, Caspase-3 and ESR1, respectively. In vitro, we found that CSSGF could suppress the expression of c-Myc or promote the expression of EGFR. In addition, we found that quercetin downregulates c-Myc expression in two BC cell lines.Conclusion: This study revealed the effective ingredients and latent molecular mechanism of action of CSSGF against TNBC and confirmed that quercetin could target c-Myc to induce anti-BC effects.Keywords: triple-negative breast cancer, chaishao shugan formula, network pharmacology, molecular docking, c-Myc

Yuqi Li,1,2,* Changjin Ji,1,2,* Weiao Sun,1,2 Huahui Xiong,1,2 Zheng Li,3 Xiaoqing Huang,1,2 Tingting Fan,1,2 Junfang Xian,3 Yaqi Huang1,2 1School of Biomedical Engineering, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Fundamental Research on Biomechanics in Clinical Application, Capital Medical University, Beijing, People’s Republic of China; 3Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yaqi Huang, School of Biomedical Engineering, Capital Medical University, Beijing, People’s Republic of China, Tel +86-10-83911809, Email yqhuang@ccmu.edu.cn Junfang Xian, Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China, Email cjr.xianjunfan@vip.163.comPurpose: Upper airway collapse during sleep in patients with obstructive sleep apnea (OSA) is a complex and dynamic phenomenon. By observing and analyzing the dynamic changes in the upper airway and its surrounding tissues during airway obstruction, we aim to reveal dynamic characteristics in different obstruction patterns, and the relationship between anatomical features during normal breathing and dynamic characteristics of airway obstruction.Patients and Methods: Dynamic MRI was performed in 23 male patients (age range 26– 63) with severe OSA diagnosed by overnight polysomnography, and obstruction events were identified from their images. Dynamic changes in parameters of the upper airway and surrounding tissues were measured to assess the key characteristics in different obstruction patterns.Results: We categorized airway obstruction into four types based on the obstruction location and motion characteristics of tissues during collapse, and detailed the alterations in the airway and surrounding tissues under each obstruction pattern. In all 112 obstruction events extracted from the dynamic images of 23 patients, type A (retropalatal obstruction caused by the soft palate separated from the tongue), BI, BII (both retropalatal obstructions caused by the soft palate attached to the tongue, and C (retropalatal and retroglossal obstruction caused by the soft palate and the tongue), accounted for 28.6%, 44.6%, 12.5%, and 14.3% respectively. In severe OSA patients with tongue and palatal obstruction related to type B or C, the more posterior hyoid position, shorter distance between tongue and uvula, and wider retropalatal space, the larger the tongue displacement and deformation during collapse, and the greater the reduction in airway space.Conclusion: There are multiple airway obstruction patterns, each with its own anatomical characteristics and behaviors during collapse. Hyoid position, tongue and uvula distance, and retropalatal space play an important role in airway collapse and should be paid more attention in the treatment of OSA.Keywords: airway obstruction patterns, obstruction location, tissue motion characteristics, hyoid position, retropalatal space

Yongde Zhou,1,* Xiaoxiao Wang,2,3,* Zhengqian Li,2,4 Yu Ma,5 Cuiping Yu,1 Yao Chen,1 Jian Ding,1 Jianfeng Yu,1 Rongsong Zhou,5 Ning Yang,2,4 Taotao Liu,2,4 Xiangyang Guo,2,4 Ting Fan,1 Chengmei Shi2,4 1Department of Anesthesiology, Tsinghua University Yuquan Hospital, Beijing, 100040, People’s Republic of China; 2Department of Anesthesiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 3Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 4Beijing Center of Quality Control and Improvement on Clinical Anesthesia, Beijing, 100191, People’s Republic of China; 5Department of Neurosurgery, Tsinghua University Yuquan Hospital, Beijing, 100040, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chengmei Shi, Department of Anesthesiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China, Tel +86-13811592813, Email shichengmei@bjmu.edu.cn Ting Fan, Department of Anesthesiology, Tsinghua University Yuquan Hospital, Beijing, 100040, People’s Republic of China, Tel +86-13681100715, Email 13681100715@163.comBackground: A simple, rapid, and effective cognitive screening test appropriate for fast-paced settings with limited resources and staff is essential, especially preoperatively. This study aimed to develop and validate the short versions of Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) for predicting postoperative delirium (POD) in patients with Parkinson’s disease (PD) who were scheduled for surgery.Methods: The current study was a secondary analysis of data collected from 128 inpatients scheduled for deep brain stimulation of the subthalamic nuclei (STN-DBS) lasting > 60 min, at Tsinghua University Yuquan Hospital, China. Preoperative cognitive screening was performed during the preoperative visit using the MMSE and MoCA. The optimal MMSE and MoCA cut-off scores for detecting PD-MCI was 27 and 23 respectively. The POD was assessed twice a day on the first postoperative day until discharge by the confusion assessment method. The backward conditional logistic regression analysis was used to organize the reduced versions of the MMSE or MoCA. Also, the areas under the receiver operating characteristic curves (AUCs) were examined using the DeLong test.Results: 125/128 PD patients were included in the analysis, and 27 (21.6%) developed POD. The MMSE reduced version (orientation to time, attention and calculation, and comprehension) demonstrated performance similar to the original MMSE in predicting POD (z=0.820, p=0.412). The AUC of the original MoCA and the short MoCA (visuospatial and executive attention and orientation) were 0.808 and 0.826, respectively. There was no significantly difference in the AUC values between the tests (z=0.561, p=0.575).Conclusion: Our simplified MMSE and MoCA could be efficiently used to identify patients at risk for POD. Also, short cognitive tests could be considered while predicting POD in fast-paced preoperative settings with limited resources and staff.Plain Language Summary: Routine preoperative cognitive screening is very important in predicting postoperative delirium.MMSE and MoCA are the most commonly used cognitive testing method which normally takes a long time.The short variant of MMSE and MoCA show a predictive performance similar to the original tests.Keywords: Parkinson’s disease, preoperative cognitive impairment, mini-mental state examination, Montreal Cognitive Assessment, postoperative delirium

Lin Chen,1,* Qi Zhang,2,* Zheng Huang,1,* Weiwei Da,1 Shuang Liu,1 Chunchun Xue,1 Chao Ding,1 Deta Chen,1 Tianyou Fan,1 Qi Shi,1 Xiaofeng Li1 1Department of Orthopedics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Traditional Chinese Medicine, Xuhui District Tianping Street Community Health Center, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaofeng Li, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 274 Middle Zhijiang Road, Shanghai, 200071, People’s Republic of China, Tel +86-13816504131, Email lixiaofeng0409@163.comPurpose: Non-specific chronic neck pain (NSCNP) is an increasingly common musculoskeletal disease and an important issue in the global healthcare system. Some studies have shown that the combination of manual therapy and exercise is effective in treating NSCNP but still with several limitations. Traditional Chinese manual therapy (tuina) is a Chinese manual therapy that consists of soft tissue manipulation and spinal manipulation. This study aims to design a randomized controlled trial to assess the effect of a tuina combined with specific therapeutic neck exercise modified protocol for NSCNP patients.Patients and Methods: This is a study protocol for a randomized, participant-, assessor- and analyst-blinded controlled trial. Eighty-eight eligible NSCNP patients will be randomly allocated into tuina combined with specific therapeutic neck exercise group (TSTE group) and tuina combined with sham therapeutic neck exercise group (TS group) in a ratio of 1:1. All participants will receive 8 treatment sessions applied in 4 weeks and then be followed up for another 12 weeks. Clinical data will be collected at baseline, during treatment phase (at the 2- and 4-week) and at the 8-, 12-, 16-week follow-ups. The primary outcome is the changes in neck pain intensity (visual analogue scale). The secondary outcomes include neck disability (Neck Disability Index), cervical range of motion (ROM), neck muscle endurance, cervical muscle cross-sectional area, cervical curvature and analgesic consumption. Adverse events will be collected and recorded throughout the study.Conclusion: We will discuss whether our tuina combined with specific therapeutic neck exercise modified protocol is more effective at improving pericervical muscle endurance, ROM, cervical muscle cross-sectional area and cervical curvature than tuina alone, thereby decreases neck pain and disability in individuals with NSCNP more effectively.Trial Registration: Chinese Clinical Trials Registry, ChiCTR2300067903. Registered on 31 January 2023.Keywords: manual therapy, non-specific neck pain, specific therapeutic exercise, randomized controlled trial

Subseasonal-to-seasonal (S2S) prediction, especially the prediction of extreme hydroclimate events such as droughts and floods, is not only scientifically challenging, but also has substantial societal impacts. Motivated by preliminary studies, the Global Energy and Water Exchanges (GEWEX)/Global Atmospheric System Study (GASS) has launched a new initiative called "Impact of Initialized Land Surface Temperature and Snowpack on Subseasonal to Seasonal Prediction"(LS4P) as the first international grass-roots effort to introduce spring land surface temperature (LST)/subsurface temperature (SUBT) anomalies over high mountain areas as a crucial factor that can lead to significant improvement in precipitation prediction through the remote effects of land-atmosphere interactions. LS4P focuses on process understanding and predictability, and hence it is different from, and complements, other international projects that focus on the operational S2S prediction. More than 40 groups worldwide have participated in this effort, including 21 Earth system models, 9 regional climate models, and 7 data groups. This paper provides an overview of the history and objectives of LS4P, provides the first-phase experimental protocol (LS4P-I) which focuses on the remote effect of the Tibetan Plateau, discusses the LST/SUBT initialization, and presents the preliminary results. Multi-model ensemble experiments and analyses of observational data have revealed that the hydroclimatic effect of the spring LST on the Tibetan Plateau is not limited to the Yangtze River basin but may have a significant large-scale impact on summer precipitation beyond East Asia and its S2S prediction. Preliminary studies and analysis have also shown that LS4P models are unable to preserve the initialized LST anomalies in producing the observed anomalies largely for two main reasons: (i) inadequacies in the land models arising from total soil depths which are too shallow and the use of simplified parameterizations, which both tend to limit the soil memory; (ii) reanalysis data, which are used for initial conditions, have large discrepancies from the observed mean state and anomalies of LST over the Tibetan Plateau. Innovative approaches have been developed to largely overcome these problems.

Yongde Zhou,1 Yu Ma,2 Cuiping Yu,1 Yao Chen,1 Jian Ding,1 Jianfeng Yu,1 Rongsong Zhou,2 Xiaoxiao Wang,3 Ting Fan,1 Chengmei Shi4 1Department of Anesthesiology, Tsinghua University Yuquan Hospital, Beijing, People’s Republic of China; 2Department of Neurosurgery, Tsinghua University Yuquan Hospital, Beijing, People’s Republic of China; 3Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, People’s Republic of China; 4Department of Anesthesiology, Peking University Third Hospital, Beijing, People’s Republic of ChinaCorrespondence: Chengmei Shi; Ting Fan, Email shichengmei@bjmu.edu.cn; 13681100715@163.comObjective: This study aimed to explore possible biomarkers of postoperative delirium (POD) of Parkinson’s disease (PD) patients received deep brain stimulation (DBS) of the subthalamic nuclei.Materials and methods: This nested case control study analyzed perioperative plasma and cerebral spinal fluid (CSF) of patients (n = 40) who developed POD undergone DBS surgery (n = 10) and those who did not (n = 30). Blood sample was collected before surgery and on the first day postoperative, CSF sample was collected at the beginning of the operation. POD was assessed by the Confusion Assessment Method (CAM) twice a day between 7:00 am and 7:00 pm after the surgery until discharge. Plasma and CSF sample from the two groups were analyzed to investigate possible biomarkers for POD in PD patients.Results: There was no difference between POD and Non-POD groups on the concentration of Interleukin 6 and Tumor Necrosis Factor-α in CSF, preoperative plasma and postoperative plasma. There was no difference between POD and Non-POD groups on the concentration of S100 calcium-binding protein β protein (S100β) and Neurofilament light chain (NFL) in preoperative plasma and postoperative plasma. The concentration of C-reactive protein (CRP), NFL and S100β were significant higher in POD group than non-POD group in CSF. The concentration of CRP was significantly higher in POD group than non-POD group in preoperative plasma and postoperative plasma. CSF concentration of S100β might be a potential biomarker for POD via the receiver operating characteristic curve analysis and the area under the curve value of 0.973.Conclusion: For PD patients received DBS surgery, CSF S100β might be a marker for aiding detection of high-risk patients with delirium. This requires further confirmation in clinical trials.Keywords: Parkinson’s disease, deep brain stimulation, cerebrospinal fluid, postoperative delirium, biomarker

Yanyu Wu,1 Shawn X Sun,1 Tao Fan2 1Global Evidence & Outcomes, Data Sciences Institute, Research and Development, Takeda Development Center Americas, Inc, Cambridge, MA, USA; 2US Health Economics and Outcomes Research, Takeda Pharmaceuticals USA, Inc, Lexington, MA, USACorrespondence: Yanyu Wu, Global Evidence & Outcomes, Data Sciences Institute, Research and Development, Takeda Development Center Americas, Inc, 40 Landsdowne Street, Cambridge, MA, USA, Tel +1 617-955-6408, Email yanyu.wu@takeda.comBackground: US patients with hemophilia A can receive prophylaxis with extended half-life recombinant factor VIII (rFVIII) products, including efmoroctocog alfa (fragment crystallizable fusion protein) and rurioctocog alfa pegol (antihemophilic factor [recombinant], PEGylated).Objective: To evaluate dosing patterns and weekly consumption of extended half-life rFVIII products in the United States.Methods: We performed a retrospective analysis using the US Specialty Pharmacy Database (2015– 2018). Included patients had a diagnosis of hemophilia A, ≥ 2 consecutive monthly claims for efmoroctocog alfa or rurioctocog alfa pegol for prophylaxis, and weight data. Outcome measures included weekly dosing frequency and dispensed weekly dose.Results: The analysis included 774 patients (efmoroctocog alfa, 506; rurioctocog alfa pegol, 268). Mean (SD) age was 24.2 (15.8) and 26.3 (14.9) years for patients receiving efmoroctocog alfa and rurioctocog alfa pegol, respectively; mean (SD) weight was 68.4 (36.8) and 79.8 (37.7) kg, respectively. The most frequent efmoroctocog alfa regimen was twice weekly (45.7%), followed by every 4 days (20.6%), every 3 days (9.1%), and 3 times per week (7.5%). The most frequent rurioctocog alfa pegol regimen was twice weekly (72.4%), followed by 3 times per week (8.7%), every 4 days (7.6%), and every 3 days (5.5%). The proportion of efmoroctocog alfa twice-weekly dispensing records increased from 31.5% to 50.9%, and every 4 days dispensing records decreased from 31.3% to 14.5% (2015– 2018). The proportion of rurioctocog alfa pegol dispensing records remained broadly stable (2016– 2018). Overall, mean (SD; median) weekly prophylactic dose was 105.4 (77.9; 92.6) IU/kg with efmoroctocog alfa, and 96.8 (41.9; 90.9) IU/kg with rurioctocog alfa pegol.Conclusion: In this database study, the most frequently observed dosing frequency was twice weekly for patients receiving efmoroctocog alfa or rurioctocog alfa pegol. The observed mean weekly consumption was slightly higher, and variation was greater, in patients receiving efmoroctocog alfa versus rurioctocog alfa pegol.Keywords: hemophilia A, fragment crystallizable fusion protein, efmoroctocog alfa, antihemophilic factor (recombinant), PEGylated, rurioctocog alfa pegol, dosing patterns

Peng Sun,1,* Duo-Jiao Fan,1,* Tao Fan,2 Xin Li,3 Xue-Ling Qi,2 Xin-Gang Zhao,2 Qi-Fei Gai2 1Baoding Second Hospital, Hebei, 071051, People’s Republic of China; 2Department of Neurosurgery Spine Center, Sanbo Brain Hospital, Capital Medical University, Beijing, 100093, People’s Republic of China; 3Department of Neurosurgery, Baoding No. 1 Central Hospital, Hebei, 071051, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tao FanDepartment of Neurosurgery Spine Center, Sanbo Brain Hospital, Capital Medical University, No. 50 Yikesong Road, Xiangshan, Haidian District, Beijing, 100093, People’s Republic of ChinaTel +86 010 62856746Fax +86 010 62856902Email fanT064@126.comObjective: The present study discusses the O6-methylguanine-DNA methyltransferase (MGMT) protein expression of spinal glioma cells and the correlation between the sensitivity of promoter methylation of the MGMT gene to chemotherapy drugs, establishes a prediction method for the sensitivity of chemotherapy drugs on spinal gliomas, providing a theoretical basis for determining the best chemotherapy regimens for clinical patients after a spinal glioma operation.Methods: A total of 67 patients, who received microsurgical resection for spinal glioma from October 2010 to June 2016, were selected for the present study. Immunohistochemistry and methylation were performed after the operation. Among these patients, 47 patients with postoperative chemotherapy were assigned as the experimental group, while 20 patients without chemotherapy were designated as the control group.Results: Among the 47 patients in the experimental group, 39 patients had no tumor recurrence after two years, while tumors increased and symptoms were aggravated in eight patients. The progression-free survival rate of chemotherapy was 82.9%, and the two-year survival rate was 100%. The adverse reactions of patients during chemotherapy were slight. Among the 20 patients in the control group, seven patients had no tumor recurrence, while 13 patients had increased tumor size, and the progression-free survival rate was 35.0%.Conclusion: Under the guidance of MGMT immunohistochemical detection and MGMT gene promoter methylation detection after surgery, chemotherapy can effectively delay tumor recurrence, prevent a reoperation, and have good safety and tolerability. This chemotherapy regimen has good prospects.Keywords: spinal cord, glioma, microscopic surgery, chemotherapy, temozolomide

Pan Gao,1,2,* Hongtao Liu,3,* Zhenzhen Yang,1,2 Yiran Hui,2,4 Zhuangzhuang Shi,2 Zhen Yang,2 Min Song,2 Menghui Yao,2 Wenfei Fan,1 Jinhua Yang,1 Yibin Hao,1 Tianli Fan2 1People’s Hospital of Zhengzhou, Zhengzhou, Henan, 450001, People’s Republic of China; 2Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China; 3Laboratory for Cell Biology, College of Life Sciences of Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China; 4University of Chinese Academy of Sciences-Shenzhen Hospital, Shenzhen, Guangdong, 518106, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tianli FanDepartment of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of ChinaEmail fantianli@zzu.edu.cnPurpose: Increasing evidence has demonstrated that animal models are imperative to investigate the potential molecular mechanism of metastasis and discover anti-metastasis drugs; however, efficient animal models to unveil the underlying mechanisms of metastasis in esophageal squamous cell carcinoma (ESCC) are limited.Methods: ESCC cell EC9706 with high invasiveness was screened by repeated Transwell assays. Its biological characteristics were identified by flow cytometry as well as by the wound healing and CCK-8 assays. Besides, the levels of epithelial–mesenchymal transition-related markers were examined using Western blotting. Parental (EC9706-I0) and subpopulation (EC9706-I3) cells were employed to establish the renal capsule model. Next, the tumor growth was detected by a live animal imaging system, and hematoxylin and eosin staining was applied to evaluate the metastatic status in ESCC.Results: EC9706-I3 cells showed rapid proliferation ability, S phase abundance, and high invasive ability; obvious upregulation in N-cadherin, Snail, Vimentin, and Bit1; and downregulation in E-cadherin. EC9706-I3 cells were less sensitive to the chemotherapy drug 5-fluorouracil than EC9706-I0 cells; however, both cell lines reached a tumorigenesis rate of 100% in the renal capsule model. The live animal imaging system revealed that the tumors derived from EC9706-I0 cells grew more slowly than those from EC9706-I3 cells at weeks 3– 14. The EC9706-I3 xenograft model displayed a spontaneous metastatic site, including kidney, heart, liver, lung, pancreas, and spleen, with a distant metastatic rate of 80%.Conclusion: Our data suggested that the metastatic model was successfully established, providing a novel platform for further exploring the molecular mechanisms of metastasis in ESCC patients.Keywords: esophageal squamous cell carcinoma, renal capsule model, spontaneous metastasis, epithelial–mesenchymal transition process

Phase matching of circularly polarized high-order harmonics driven by counter-rotating bi-chromatic lasers was recently predicted theoretically and demonstrated experimentally. In that work, phase matching was analyzed by assuming that the total energy, spin angular momentum and linear momentum of the photons participating in the process are conserved. Here we propose a new perspective on phase matching of circularly polarized high harmonics. We derive an extended phase matching condition by requiring a new propagation matching condition between the classical vectorial bi-chromatic laser pump and harmonics fields. This allows us to include the influence of the laser pulse envelopes on phase matching. We find that the helicity dependent phase matching facilitates generation of high harmonics beams with a high degree of chirality. Indeed, we present an experimentally measured chiral spectrum that can support a train of attosecond pulses with a high degree of circular polarization. Moreover, while the degree of circularity of the most intense pulse approaches unity, all other pulses exhibit reduced circularity. This feature suggests the possibility of using a train of attosecond pulses as an isolated attosecond probe for chiral-sensitive experiments.

We demonstrate, to our knowledge, the first bright circularly polarized high-harmonic beams in the soft X-ray region of the electromagnetic spectrum, and use them to implement X-ray magnetic circular dichroism measurements in a tabletop-scale setup. Using counterrotating circularly polarized laser fields at 1.3 and 0.79 μm, we generate circularly polarized harmonics with photon energies exceeding160 eV. The harmonic spectra emerge as a sequence of closely spaced pairs of left and right circularly polarized peaks, with energies determined by conservation of energy and spin angular momentum. We explain the single-atom and macroscopic physics by identifying the dominant electron quantum trajectories and optimal phasematching conditions. The first advanced phase-matched propagation simulations for circularly polarized harmonics reveal the influence of the finite phase-matching temporal window on the spectrum, as well as the unique polarization-shaped attosecond pulse train. Finally, we use, to our knowledge, the first tabletop X-ray magnetic circular dichroism measurements at the N4,5 absorption edges of Gd to validate the high degree of circularity, brightness, and stability of this light source. These results demonstrate the feasibility of manipulating the polarization, spectrum, and temporal shape of high harmonics in the soft X-ray region by manipulating the driving laser waveform.

Yufan Jian,1,2,* Meina Zhao,1,2,* Jinyi Cao,1,* Tingting Fan,1 Wei Bu,1 Yang Yang,3 Weiwei Li,1 Wei Zhang,1 Yi Qiao,1 Jingwen Wang,1 Aidong Wen1,2 1Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi’an 710032, People’s Republic of China; 2College of Pharmacy, Shannxi University of Chinese Medicine, Xianyang 712046, People’s Republic of China; 3Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tingting Fan; Aidong WenDepartment of Pharmacy, Xijing Hospital, The Air Force Military Medical University, Xi’an 710032, People’s Republic of ChinaEmail fanting0427@163.com; adwen-2004@hotmail.comAim: The aim of this study was to develop a GX1-modified nanostructured lipid carrier (NLCs) and to evaluate its ability to improve the anti-gastric cancer tumor effects of paclitaxel (PTX).Main Methods: The GX1-modified NLCs were synthesized and loaded with PTX (GX1-PTX-NLCs) by emulsion solvent evaporation technique. The anti-tumor activity and pharmacodynamics were then evaluated by in vitro cell studies and animal experiments.Key Findings: The GX1-modified NLCs were successfully synthesized and confirmed by 1H NMR and MALDI-TOF-MS. PTX-loaded NLCs produced particles with average size distribution less than or equal to 222 nm and good drug loading and entrapment efficiency. In vitro studies demonstrated that GX1-PTX-NLCs had a more obvious inhibitory effect on Co-HUVEC cells than PTX and unmodified PTX-NLCs. The cellular uptake results also showed that GX1-PTX-NLCs were largely concentrated in Co-HUVEC cells, and the uptake rates of GX1-PTX-NLCs in Co-HUVEC were higher than those of the free drug and the PTX-NLC. In vivo studies demonstrated that GX1-PTX-NLCs possess strong anti-tumor effect and showed higher tumor growth inhibition and lower toxicity in nude mice.Significance: These results suggest that GX1-modified NLCs enhanced the anti-tumor activity of PTX and reduced its toxicity effectively. GX1-PTX-NLCs may be considered as a potent drug delivery system for therapy of gastric cancer.Keywords: gastric cancer, paclitaxel, nano-lipid carriers, gastric cancer peptide, anti-tumor activity

OBJECTIVE: The pathogenesis of Parkinson's disease (PD) is associated with abnormal iron accumulation. Magnetic resonance imaging (MRI) studies have shown that patients with Parkinson's disease have an increased amount of iron in their substantia nigra (SN). We have undertaken a meta-analysis of studies using MRI in PD, to explore the potential role of MRI in diagnosing PD using abnormal iron deposition in SN as a candidate biomarker. MATERIALS AND METHODS: Searches of PubMed, Embase, and Medline databases revealed 16 studies that compared PD patients and healthy controls (HC). A sensitivity analysis and subgroup analysis were performed to evaluate the reliability of our results. Estimates were pooled by the fixed-effects model. As an expression of I2, we computed the proportion of variation due to heterogeneity. RESULTS: We i ncluded 16 s tudies with s ample sizes of 435 PD and 355 HC in our meta-analysis. Results showed that SN iron deposition was significantly elevated (p<0.00001) in patients with PD compared to HC ones (SMD=0.72, 95% confidence interval 0.57 to 0.87, p<0.00001). CONCLUSIONS: Our findings, based on a homogeneous group-level analysis, suggest that MRI-based SN iron deposition could be used to distinguish PD from HC. For a more rigorous investigation of SN iron deposition in PD, larger cohort studies are needed. [ABSTRACT FROM AUTHOR]

China has to perform high-intensity and high-chemical input agricultural production to improve its food security, which has caused uncertainty in the development of ecological agriculture. This study utilizes bibliometrics and spatial statistical methods to examine the representative literature on ecological agriculture published in the CNKI database from 2012 to 2023. The findings reveal that keywords such as rural revitalization, modern agriculture, and ecological tourism are frequently mentioned while emerging interests include carbon neutrality, eco-circular agriculture, and industrial integration. The main clusters of keywords can be classified into specific practical research, general studies, and countermeasures orderly. The themes of ecological tourism, developing mode, and rural revitalization have attracted long-lasting concerns in research over the past decade. Spatial statistical analysis indicates that, aside from the Eastern coastal areas, most provinces in China exhibit insufficient collaboration and limited spill-over effects in research of ecological agriculture, highlighting the necessity for enhanced integration. This study also provides recommendations to address the prevailing challenges to food security through the promotion of ecological agriculture in China. [ABSTRACT FROM AUTHOR]

Jay Lin,1 Melissa Lingohr-Smith,1 Tao Fan2 1Health Economics and Outcomes Research, Novosys Health, Green Brook, NJ, USA; 2North America Medical Affairs, Sanofi US, Inc., Bridgewater, NJ, USA Background: Free-dose combination treatment with basal insulin and short-acting glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduces hyperglycemia via complementary targeting of fasting and postprandial blood glucose levels, however, in the real world, due to injection burden and clinical inertia, the full efficacy may not be able to translate into clinical and economic benefits. Objective: The aim of the study was to evaluate treatment persistence and associated outcomes in patients with type 2 diabetes (T2D) treated with a GLP-1 RA in free-dose combination with basal insulin. Methods: Claims data were extracted on US adults with T2D with ≥1 prescription claim for both a GLP-1 RA and a basal insulin from July 1, 2008 to June 30, 2013, and continuous health plan coverage for 6 months prior to (baseline) and 12 months after the index date (follow-up period). Outcomes analyzed for patients stratified by treatment persistence included glycemic control, hypoglycemia, and health care costs and resource utilization. Multivariate analyses were used to examine factors associated with persistence or hypoglycemia. Results: The analysis included 7,320 patients, of whom 16.9% were persistent with free-dose combination treatment. The median time to treatment discontinuation was 133 days. Compared with ­nonpersistent patients, persistent patients had greater glycated hemoglobin A1c (A1C) reductions (–0.80% vs –0.42%; P=0.032), were more likely to achieve A1C

Xiaoli Wang,1,2,* Yijun Luo,1,2,* Minghuan Li,2 Hongjiang Yan,2 Mingping Sun,2 Tingyong Fan2 1School of Medicine and Life Sciences, Jinan University-Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong, People’s Republic of China *These authors contributed equally to this work Background: Postoperative radiotherapy has shown positive efficacy in lowering the recurrence rate and improving the survival rate for patients with esophageal squamous cell carcinoma (ESCC). However, controversies still exist about the postoperative prophylactic radiation target volume. This study was designed to analyze the patterns of recurrence and to provide a reference for determination of the postoperative radiotherapy target volume for patients with midthoracic ESCC.Patients and methods: A total of 338 patients with recurrent or metastatic midthoracic ESCC after radical surgery were retrospectively examined. The patterns of recurrence including locoregional and distant metastasis were analyzed for these patients.Results: The rates of lymph node (LN) metastasis were 28.4% supraclavicular, 77.2% upper mediastinal, 32.0% middle mediastinal, 50.0% lower mediastinal, and 19.5% abdominal LNs. In subgroup analyses, the rate of abdominal LN metastasis was significantly higher in patients with histological node-positive than that in patients with histological node-negative (P=0.033). Further analysis in patients with histological node-positive demonstrated that patients with three or more positive nodes are more prone to abdominal LN metastasis, compared with patients with one or two positive nodes (χ2=4.367, P=0.037). The length of tumor and histological differentiation were also the high-risk factors for abdominal LN metastasis.Conclusion: For midthoracic ESCC with histological node-negative, or one or two positive nodes, the supraclavicular and stations 2, 4, 5, and 7 LNs should be delineated as clinical target volume of postoperative prophylactic irradiation, and upper abdominal LNs should be excluded. While for midthoracic ESCC with three or more positive nodes, upper abdominal LNs should also be included. The length of tumor and histological differentiation should be considered comprehensively to design the clinical target volume for radiotherapy. Keywords: esophagus cancer, radiotherapy, recurrence and metastasis, clinical target volume

Trehalose has been extensively studied in the application of fruit preservation, but little has been reported in cherry tomato preservation. The present work investigated the effects of postharvest trehalose treatment on cherry tomato spoilage rate, antioxidant capacity, and fruit quality through the application of 0.5 and 1% (w/v) trehalose. Our results indicated that trehalose treatment could reduce rot from 44.5 to 18.5%, maintain the fruit flavour and quality, and delay the decrease in antioxidant content. At 15 d postharvest, the diphenyl-picryl hydrazide (DPPH) scavenging capacity, superoxide anion (·O2-) production, and malonaldehyde (MDA) content were 78.1%, 1.04 mmol.min-1.kg-1, and 0.8 µmol.kg-1 in cherry tomato treated with 0.5% (w/v) trehalose, respectively. Trehalosetreated fruits maintained higher antioxidant capacities as compared to the control. Moreover, trehalose treatment increased the activities of superoxidase dismutase (SOD) and ascorbate peroxidase (APX), and inhibited the activity of lipoxygenase (LOX). The expression of encoding antioxidant genes was generally upregulated under trehalose treatment. However, the expression of SlLOX gene was significantly lower during storage, at only one-tenth of the control at 9 d. In conclusion, trehalose treatment had positive effects on decreasing decay incidence by increasing antioxidant capacity in cherry tomato. [ABSTRACT FROM AUTHOR]