Search

We study parton energy-momentum exchange with the quark gluon plasma (QGP) within a multistage approach composed of in-medium Dokshitzer-Gribov-Lipatov-Altarelli-Parisi evolution at high virtuality, and (linearized) Boltzmann transport formalism at lower virtuality. This multistage simulation is then calibrated in comparison with high-pT charged hadrons, D mesons, and the inclusive jet nuclear modification factors, using Bayesian model-to-data comparison, to extract the virtuality-dependent transverse momentum broadening transport coefficient q. To facilitate this undertaking, we develop a quantitative metric for validating the Bayesian workflow, which is used to analyze the sensitivity of various model parameters to individual observables. The usefulness of this new metric in improving Bayesian model emulation is shown to be highly beneficial for future such analyses.

Xiaojing Wang, Qinli Guo, Zhaoxiang Liu, Yanlei Wang, Chenxiang Cao, Lixia Jin, Caihong Li, Jianzhong Xiao, Wenhui Zhao Department of Endocrinology, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, People’s Republic of ChinaCorrespondence: Wenhui Zhao, Department of Endocrinology, Beijing Tsinghua Changgung Hospital, LiTang Lu No. 168, Chang Ping District, Beijing, 102218, People’s Republic of China, Tel +86-13810719795, Email zwha01637@btch.edu.cnPurpose: Obesity has become a major public health concern worldwide, increasing the risk of T2DM. Growing evidence indicates gut microbiota dysbiosis is related to metabolic disorders. We aimed to firstly investigate the compositional and functional features of the gut microbiome between obesity with and without T2DM in the Chinese population.Methods: A total of 32 obese individuals accompanied with T2DM and 18 age and gender-matched obesity with normal glucose tolerance (NGT) were enrolled. Fecal samples were collected, and the gut microbiota profile was determined using the Illumina MiSeq platform based on V3-V4 bacterial 16S rRNA gene.Results: Compared with obesity- NGT, obesity-T2DM showed a significantly higher alpha diversity. Principal coordinates analysis based on both Bray-Curtis distance and weighted Unifrac revealed that the global microbial composition was significantly different between the two groups (P = 0.007 and P = 0.005, respectively). At the phylum level, Obesity-T2DM patients exhibited a significant decrease in Bacteroidetes, and a pronounced increase in Firmicutes. Regarding the genus level, Bacteroides and Escherichia-Shigella were found to increase considerably, while Prevotella_9 and Sutterella had an evident decrease in Obesity-T2DM. Furthermore, Spearman correlation analysis revealed that Prevotella_9 and Sutterella were negatively associated with HbA1c and fasting blood glucose.Conclusion: We found clear differences in the gut microbiota composition in obesity-T2DM compared with obesity-NGT. Obesity accompanied with T2DM may aggravate the obesity-associated gut microbiota, and gut microbiota is expected to be a promising novel intervention target for obese management. However, larger sample size and more in-depth taxonomic identification studies are warranted.Keywords: gut microbiota, obesity, type 2 diabetes

Xiangan Gong,1,2 Qian Zhao,1,2 Huimin Zhang,1,2 Rui Liu,1,2 Jie Wu,1,2 Nanxin Zhang,3 Yuanxian Zou,1,2 Wen Zhao,1,2 Ran Huo,1,2,4 Rongtao Cui1– 4 1Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 3School of Clinical Medicine, Shandong Second Medical University, Weifang, People’s Republic of China; 4Department of Burn and Plastic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Rongtao Cui, Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Tel +86 18653170822, Email cuirt1986@outlook.comAbstract: Pathological scarring results from aberrant cutaneous wound healing due to the overactivation of biological behaviors of human skin fibroblasts, characterized by local inordinate inflammation, excessive extracellular matrix and collagen deposition. Yet, its underlying pathogenesis opinions vary, which could be caused by increased local mechanical tension, enhanced and continuous inflammation, gene mutation, as well as cellular metabolic disorder, etc. Metabolic reprogramming is the process by which the metabolic pattern of cells undergoes a systematic adjustment and transformation to adapt to the changes of the external environment and meet the needs of their growth and differentiation. Therefore, the abnormality of metabolic reprogramming in cells within wounds and scars attaches great importance to scar formation. Mesenchymal stem cells-derived exosomes (MSC-Exo) are the extracellular vesicles that play an important role in tissue repair, cancer treatment as well as immune and metabolic regulation. However, there is not a systematic work to detail the relevant studies. Herein, we gave a comprehensive summary of the existing research on three main metabolisms, including glycometabolism, lipid metabolism and amino acid metabolism, and MSC-Exo regulating metabolic reprogramming in wound healing and scar formation for further research reference.Keywords: mesenchymal stem cells-derived exosomes, metabolic reprogramming, scar, wound healing, fibroblast

Jing Wang,1,* Lei Tian,2,* Weilong Zhang,1,* Shuhan Tang,1 Wei Zhao,1 Yu Guo,1 Chaoling Wu,1 Yuansheng Lin,1 Xiaoyan Ke,1 Hongmei Jing1 1Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Health Management Center, Peking University Third Hospital, Beijing, 100191, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoyan Ke; Hongmei Jing, Email xykbysy@163.com; hongmeijing@bjmu.edu.cnBackground: The application of rituximab has significantly enhanced the overall survival rates in patients with diffuse large B-cell lymphoma (DLBCL). Regrettably, a significant number of patients still progress to relapse/refractory DLBCL (rrDLBCL).Methods: Herein, we employed targeted sequencing of 55 genes to investigate if gene mutations could predict the progression to rrDLBCL. Additionally, we compared the mutation profiles at the time of DLBCL diagnosis with those found in rrDLBCL cases.Results: Our findings highlighted significantly elevated mutation frequencies of TP53, MEF2B and CD58 in diagnostic biopsies from patients who progressed to relapse or refractory disease, with CD58 mutations exclusively observed in the rrDLBCL group. In assessing the predictive power of mutation profiles for treatment responses in primary DLBCL patients, we found that the frequency of CARD11 mutations was substantially higher in non-response group as compared with those who responded to immunochemotherapy. In addition, we revealed mutations in HIST2H2AB, BCL2, NRXN3, FOXO1, HIST1H1C, LYN and TBL1XR1 genes were only detected in initial diagnostic biopsies, mutations in the EBF1 gene were solely detected in the rrDLBCL patients.Conclusion: Collectively, this study elucidates some of the genetic mechanisms contributing to the progression of rrDLBCL and suggests that the presence of CD58 mutations might serve as a powerful predictive marker for relapse/refractory outcomes in primary DLBCL patients.Keywords: targeted sequencing, mutation profile, relapse/refractory disease, diffuse large B-cell lymphoma

Tingting Wang,1 Juntao Tan,2 Tiantian Wang,2 Shoushu Xiang,2 Yang Zhang,1 Chang Jian,1 Jie Jian,1 Wenlong Zhao1,3 1College of Medical Informatics, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Operation Management Office, Affiliated Banan Hospital of Chongqing Medical University, Chongqing, 401320, People’s Republic of China; 3Medical Data Science Academy, Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Wenlong Zhao, College of Medical Informatics, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-13883163651, Email cqzhaowl@163.comPurpose: Hospitalized hypertensive patients rely on blood pressure medication, yet there is limited research on the sole use of amlodipine, despite its proven efficacy in protecting target organs and reducing mortality. This study aims to identify key indicators influencing the efficacy of amlodipine, thereby enhancing treatment outcomes.Patients and Methods: In this multicenter retrospective study, 870 hospitalized patients with primary hypertension exclusively received amlodipine for the first 5 days after admission, and their medical records contained comprehensive blood pressure records. They were categorized into success (n=479) and failure (n=391) groups based on average blood pressure control efficacy. Predictive models were constructed using six machine learning algorithms. Evaluation metrics encompassed the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). SHapley Additive exPlanations (SHAP) analysis assessed feature contributions to efficacy.Results: All six machine learning models demonstrated superior predictive performance. Following variable reduction, the model predicting amlodipine efficacy was reconstructed using these algorithms, with the light gradient boosting machine (LightGBM) model achieving the highest overall performance (AUC = 0.803). Notably, amlodipine showed enhanced efficacy in patients with low platelet distribution width (PDW) values, as well as high hematocrit (HCT) and thrombin time (TT) values.Conclusion: This study utilized machine learning to predict amlodipine’s effectiveness in hypertension treatment, pinpointing key factors: HCT, PDW, and TT levels. Lower PDW, along with higher HCT and TT, correlated with enhanced treatment outcomes. This facilitates personalized treatment, particularly for hospitalized hypertensive patients undergoing amlodipine monotherapy.Keywords: anti-hypertensive drugs, hypertension, machine learning, shapley additive explanations

Jiachen Yu,1,* Yingchun Zhang,1,* Rong Ran,2,* Zixiao Kong,3 Duoyi Zhao,1 Wei Zhao,1 Yingxin Yang,4 Lianbo Gao,5 Zhiyu Zhang1 1Department of Orthopedics, the Fourth Affiliated Hospital of China Medical University, China Medical University, Shen Yang, 110032, People’s Republic of China; 2Department of Anesthesia, the Fourth Affiliated Hospital of China Medical University, China Medical University, Shen Yang, 110032, People’s Republic of China; 3China Medical University, Shen Yang, 110032, People’s Republic of China; 4General Hospital of Northern Theater Command, China Medical University, Shen Yang, 110032, People’s Republic of China; 5Department of Neurology, the Fourth Affiliated Hospital of China Medical University, China Medical University, Shen Yang, 110032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiyu Zhang; Lianbo Gao, The Fourth Affiliated Hospital of China Medical University, No. 4 Chongshan Road, Huanggu District, Shenyang, Liaoning, People’s Republic of China, Email zyzhang@cmu.edu.cn; lbgao@cmu.edu.cnAbstract: The development of therapeutic drugs and methods has been greatly facilitated by the emergence of tumor models. However, due to their inherent complexity, establishing a model that can fully replicate the tumor tissue situation remains extremely challenging. With the development of tissue engineering, the advancement of bioprinting technology has facilitated the upgrading of tumor models. This article focuses on the latest advancements in bioprinting, specifically highlighting the construction of 3D tumor models, and underscores the integration of these two technologies. Furthermore, it discusses the challenges and future directions of related techniques, while also emphasizing the effective recreation of the tumor microenvironment through the emergence of 3D tumor models that resemble in vitro organs, thereby accelerating the development of new anticancer therapies.Keywords: bioprinting, bioink, organoids, tumor spheroids, tumor chips

Jing Luo,1,2 Yi Luo,2 Maoru Zhao,3 Yulong Liu,2 Jiayin Liu,2 Zhulin Du,2 Hong Gong,2 Lian Wang,2 Jinghui Zhao,2 Xiaqing Wang,2 Zhanjun Gu,3 Wenhui Zhao,1 Tianyao Liu,2 Xiaotang Fan2 1School of Life Sciences, Chongqing University, Chongqing, 401331, People’s Republic of China; 2Department of Military Cognitive Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing, 400038, People’s Republic of China; 3Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, Institute of High Energy Physics and National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100049, People’s Republic of ChinaCorrespondence: Xiaotang Fan; Tianyao Liu, Email fanxiaotang2005@163.com; squall277@163.comBackground: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects social interaction and communication and can cause stereotypic behavior. Fullerenols, a type of carbon nanomaterial known for its neuroprotective properties, have not yet been studied for their potential in treating ASD. We aimed to investigate its role in improving autistic behaviors in BTBR T+Itpr3tf/J (BTBR) mice and its underlying mechanism, which could provide reliable clues for future ASD treatments.Methods: Our research involved treating C57BL/6J (C57) and BTBR mice with either 0.9% NaCl or fullerenols (10 mg/kg) daily for one week at seven weeks of age. We then conducted ASD-related behavioral tests in the eighth week and used RNA-seq to screen for vital pathways in the mouse hippocampus. Additionally, we used real-time quantitative PCR (RT-qPCR) to verify related pathway genes and evaluated the number of stem cells in the hippocampal dentate gyrus (DG) by Immunofluorescence staining.Results: Our findings revealed that fullerenols treatment significantly improved the related ASD-like behaviors of BTBR mice, manifested by enhanced social ability and improved cognitive deficits. Immunofluorescence results showed that fullerenols treatment increased the number of DCX+ and SOX2+/GFAP+ cells in the DG region of BTBR mice, indicating an expanded neural progenitor cell (NPC) pool of BTBR mice. RNA-seq analysis of the mouse hippocampus showed that VEGFA was involved in the rescued hippocampal neurogenesis by fullerenols treatment.Conclusion: In conclusion, our findings suggest that fullerenols treatment improves ASD-like behavior in BTBR mice by upregulating VEGFA, making nanoparticle- fullerenols a promising drug for ASD treatment. Keywords: fullerenols, BTBR, neurogenesis, autism spectrum disorder, hippocampus

Yanzhi Feng,1– 4,* Litao Liang,1– 4,* Wenbo Jia,1– 4 Jinyi Wang,1– 4 Chao Xu,1– 4 Deming Zhu,1– 4 Bin Xu,1– 4 Wenhu Zhao,1– 4 Xiangyu Ling,1– 4 Yongping Zhou,5 Lianbao Kong,1– 4,* Wenzhou Ding1– 4,* 1Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, National Health Commission Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, Jiangsu, People’s Republic of China; 3Jiangsu Provincial Medical Innovation Center, Nanjing, Jiangsu, People’s Republic of China; 4Jiangsu Provincial Medical Key Laboratory, Nanjing, Jiangsu, People’s Republic of China; 5Jiangnan University Medical Center, JUMC, Department of Hepatobiliary, Wuxi, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenzhou Ding; Lianbao Kong, Hepatobiliary Centre, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Email dingwenzhou@njmu.edu.cn; lbkong@njmu.edu.cnBackground: Circular RNAs (circRNAs) have been shown to play a crucial role in the initiation and development of Hepatocellular carcinoma (HCC). However, the mechanism and function of circ_0007386 in HCC are still unknown.Methods: Circ_0007386 expression level in HCC tissues, and HCC cell lines was further analyzed by qRT-PCR. Agarose gel electrophoresis and Sanger sequencing were used to figure out the structure of circ_0007386. The involvement of circ_0007386 in HCC development was evaluated by experimental investigations conducted in both laboratory settings (in vitro) and living organisms (in vivo). RNA immunoprecipitation, Western blotting, luciferase reporter assay and fluorescence in situ hybridization (FISH) were applied for finding out the interaction among circ_0007386, miR-507 and CCNT2. To assess the connection between circ_0007386 and lenvatinib resistance, lenvatinib-resistant HCC cell lines were employed.Results: The expression of circ_0007386 was found to increase in HCC tissues, and it was observed to be associated with a worse prognosis. Overexpression of circ_0007386 stimulated HCC cells proliferation, invasion, migration and the epithelial–mesenchymal transition (EMT) while silencing of circ_0007386 resulted in the opposite effect. Mechanistic investigations revealed that circ_0007386 acted as a competing endogenous RNA of miR-507 to prevent CCNT2 downregulation. Downregulating miR-507 or overexpressing CCNT2 could reverse phenotypic alterations that originated from inhibiting of circ_0007386. Importantly, circ_0007386 determines the resistance of hepatoma cells to lenvatinib treatment.Conclusion: Circ_0007386 advanced HCC progression and lenvatinib resistance through the miR-507/ CCNT2 axis. Meanwhile, circ_0007386 served as a potential biomarker and therapeutic target in HCC patients. Keywords: hepatocellular carcinoma, circ_0007386, miR-507, CCNT2, Lenvatinib

Jufei Wu,1,&ast; Jishi Wu,2,&ast; Yan Zhou,3 Xiaohua Lu,4 Wane Zhao,4 Fengmei Xu1 1Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2Department of General Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 3Department of Interventional Radiology & Vascular Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 4Department of Endocrinology, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Zhou, Department of Interventional Radiology & Vascular Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China, Email 992054881@qq.com Xiaohua Lu, Department of Endocrinology, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China, Email yhlu@163.comPurpose: To develop a prediction model for hypoglycemia in type 2 diabetes mellitus (T2DM) patients treated with an insulin pump during enteral nutrition.Methods: This retrospective study included T2DM patients treated with an insulin pump during enteral nutrition at the First Affiliated Hospital of Jinan University, Guangzhou Red Cross Hospital, Foshan First People’s Hospital, and Guangdong Provincial Hospital of Traditional Chinese Medicine between January 2016 and December 2023. The patients were randomized 3:1 to the training and validation sets. The risk factors for hypoglycemia were analyzed. A prediction model was developed.Results: This study included 122 patients, and 57 patients had at least one hypoglycemic event during their hospitalization (46.72%). The multivariable logistic regression analysis showed that the time to reach the glycemic targets (odds ratio (OR)=1.408, 95% confidence interval (CI)=1.084– 1.825, P=0.006), average glycemia (OR=0.387, 95% CI=0.233– 0.643, P=0.010), coronary heart disease (OR=0.089, 95% CI=0.016– 0.497, P< 0.001), and the administration of hormone therapy (OR=6.807, 95% CI=1.128– 41.081, P=0.037) were independently associated with hypoglycemia. A nomogram was built. The receiver operating characteristics analysis showed that the area under the curve of the model was 0.872 (95% CI=0.0.803– 0.940) for the training set and 0.839 (95% CI=0.688– 0.991) in the validation set.Conclusion: A nomogram was successfully built to predict hypoglycemia in T2DM patients treated with an insulin pump during enteral nutrition, based on the time to reach the glycemic targets, average glycemia, coronary heart disease, and the administration of hormone therapy.Keywords: T2DM, hypoglycemia, enteral nutrition, insulin pump therapy, nomograms

Lang Liu,1,&ast; Binghua Zhang,1,&ast; Zhenwei Zhou,2 Jie Yang,1 Ailin Li,1 Yongji Wu,1 Zeyu Peng,1 Xiangyan Li,2 Zhonghua Liu,3 Xiangyang Leng,1 Changwei Zhao,4 Haisi Dong,2 Wenhai Zhao4 1College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 2Northeast Asia Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 3Department of Orthopaedics, The Third Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 4Affiliated Hospital of Changchun University of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haisi Dong, Northeast Asia Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, People’s Republic of China, Tel/Fax +86 431-18604361976, Email adonghaisi@163.com Wenhai Zhao, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, 130021, People’s Republic of China, Tel/Fax +86 431-86177836, Email zwh9899@163.comBackground: Knee osteoarthritis (KOA) is a persistent degenerative condition characterized by the deterioration of cartilage. The Chinese herbal formula Radix Rehmanniae Praeparata- Angelica Sinensis-Radix Achyranthis Bidentatae (RAR) has often been used in effective prescriptions for KOA as the main functional drug, but its underlying mechanism remains unclear. Therefore, network pharmacology and verification experiments were employed to investigate the impact and mode of action of RAR in the treatment of KOA.Methods: The destabilization of the medial meniscus model (DMM) was utilized to assess the anti-KOA effect of RAR by using gait analysis, micro-computed tomography (Micro-CT), and histology. Primary chondrocytes were extracted from the rib cartilage of a newborn mouse. The protective effects of RAR on OA cells were evaluated using a CCK‐8 assay. The antioxidative effect of RAR was determined by measuring reactive oxygen species (ROS), superoxide dismutase (SOD), and glutathione (GSH) production. Furthermore, network pharmacology and molecular docking were utilized to propose possible RAR targets for KOA, which were further verified through experiments.Results: In vivo, RAR significantly ameliorated DMM-induced KOA characteristics, such as subchondral bone sclerosis, cartilage deterioration, gait abnormalities, and the degree of knee swelling. In vitro, RAR stimulated chondrocyte proliferation and the expression of Col2a1, Comp, and Acan. Moreover, RAR treatment significantly reduced ROS accumulation in an OA cell model induced by IL-1β and increased the activity of antioxidant enzymes (SOD and GSH). Network pharmacology analysis combined with molecular docking showed that Mapk1 might be a key therapeutic target. Subsequent research showed that RAR could downregulate Mapk1 mRNA levels in IL-1β-induced chondrocytes and DMM-induced rats.Conclusion: RAR inhibited extracellular matrix (ECM) degradation and oxidative stress response via the MAPK signaling pathway in KOA, and Mapk1 may be a core target.Keywords: knee osteoarthritis, RAR, cartilage degeneration, network pharmacology, Mapk1

Qinghao Liu,&ast; Weiwen Zhao,&ast; Hao Yin Department of Orthopedic, The First Affiliated Hospital of Hunan Normal University Hunan Provincial People’s Hospital, Changsha, China Mainland (PRC)&ast;These authors contributed equally to this workCorrespondence: Hao Yin, Email ehour@hunnu.edu.cnBackground: Spontaneous spinal epidural hematoma (SSEH) presenting in the context of JAK2 V617F-positive myeloproliferative neoplasms is a rare condition, characterized by the compression of the spinal cord leading to various symptoms. The etiology, pathogenesis, and optimal treatment strategies for this condition remain undetermined. The occurrence of spontaneous spinal epidural hematoma (SSEH) in the context of JAK2 V617F-positive myeloproliferative neoplasms (MPNs) represents a rare manifestation. Magnetic Resonance Imaging (MRI) plays a crucial role in the definitive diagnosis of this condition. With a good understanding of the pathogenic characteristics and clinical presentations of this disease, a diagnosis can be reasonably made, even in the absence of MRI, based on physical examinations indicating the affected area. Once diagnosed, immediate surgery is recommended to attempt the restoration of spinal cord function. Postoperatively, the use of hydroxyurea has proven effective in disease control.Case Presentation: We report a case of a 65-year-old male patient who presented with progressive lumbar back pain and bilateral lower limb paralysis lasting for 36 hours. CT imaging revealed an intraspinal lesion at the L1-3 level, and genetic testing confirmed the presence of the JAK2V617F mutation. Following surgery, there was a significant recovery of sensory and motor function in the lower limbs. At one-year follow-up, the patient demonstrated good functional status, and blood tests indicated a platelet count within the normal range.Conclusion: The presented case adds to the existing literature on SSEH by highlighting the association with myeloproliferative neoplasms (MPNs), as evidenced by the JAK2V617F mutation. MPNs constitute a group of hematologic malignancies, and the association with SSEH is a rare occurrence. The exact interplay between MPNs and SSEH warrants further investigation, as the underlying mechanisms linking these conditions remain elusive. The case also underscores the importance of a multidisciplinary approach, involving hematologists and neurosurgeons, in the comprehensive management of such complex cases.Keywords: myeloproliferative neoplasms, spinal epidural hematoma, JAK2V617F

Yanlei Wang,&ast; Zhaoxiang Liu,&ast; Wenhui Zhao, Chenxiang Cao, Luqi Xiao, Jianzhong Xiao Department of Endocrinology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, 102218, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianzhong Xiao, Department of Endocrinology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, No. 168 Litang Road, Changping District, Beijing, 102218, People’s Republic of China, Tel/Fax +8610-5611-9057, Email xjza01150@btch.edu.cnBackground: Von Hippel-Lindau (VHL) syndrome is characterized by tumorous lesions affecting multiple organs. Pancreatic involvement in VHL syndrome can present as endocrine tumors and pancreatic cysts, which can interfere with both exocrine and endocrine functions of the pancreas. Diabetes is an uncommon complication of VHL syndrome.Purpose: This study aims to summarize the various mechanisms of diabetes in VHL syndrome by reporting two cases and conducting a literature review.Methods: We analyzed the clinical and imaging data of two patients with VHL syndrome and diabetes. Additionally, we reviewed the existing literature to explore the clinical diversities and management strategies for VHL syndrome complicated with diabetes.Results: The first patient presented with liver metastasis of pancreatic neuroendocrine tumor and multiple pheochromocytoma. After surgery, the patient’s diabetic control improved, as evidenced by a significant reduction in insulin dosage. This indicates a potential insulin resistance due to elevated metanephrine levels prior to surgery and partial insulin deficiency caused by distal pancreatectomy. The second patient had multiple hemangioblastomas, as well as multiple pancreatic cysts and positive pancreatic islet autoantibodies. Diabetes in this case may be attributed to pancreatic lesions and the coexistence of autoimmune insulitis. A literature review of other patients with VHL combined with diabetes revealed multiple mechanisms, including increased catecholamine levels, pancreatic lesions, surgical removal of pancreatic tissue, endocrine treatment, and possibly the coexistence of autoimmune insulitis.Conclusion: VHL syndrome complicated with diabetes involves diverse mechanisms.Keywords: von Hippel-Lindau syndrome, diabetes, pancreatic neuroendocrine tumor

Jing Zhang,1,2 Ke Ma,3 Jun Yan,4 Pingsheng Pan,5 Jiangshan Yin,6 Fuqing Lin,7 Hui Chen,8 Weiwei Zhao,1,2 Menglei Chen,1,2 Zhe Zhang,1,2 Minghui Liu,1,2 Xiaoli Gu,1,2 Xinghe Liao,1,2 Chenyue Zhang,1,2 Wenwu Cheng1,2 1Department of Integrated Therapy, Shanghai Cancer Center, Fudan University, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Department of Pain Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Oncology, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China; 5Department of Oncology, Fangta Hospital of Traditional Chinese Medicine in Songjiang District, Shanghai, People’s Republic of China; 6Department of Oncology, Fudan University Shanghai Cancer Center, Minhang Branch, Shanghai, People’s Republic of China; 7Department of Anaesthesiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 8Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Wenwu Cheng, Email cwwxxm@sina.comPurpose: This study aimed to assess the current status of clinical practice of refractory cancer pain (RCP) among a sample of physicians specializing in cancer pain management in Shanghai.Methods: From 2019 to 2021, a questionnaire survey was conducted among physicians engaged in diagnosis and treatment of cancer pain through the questionnaire WJX network platform in Shanghai, China.Results: A total of 238 responses participated in the survey. This survey reports physicians’ understanding and incidence rate of breakthrough cancer pain (BTCP). The choice of analgesics and satisfaction of analgesic effect were investigated. We also investigated doctors’ knowledge of the diagnostic criteria for RCP and their tendency to choose analgesics. Oral immediate-release morphine and intravenous or subcutaneous morphine injection have been the common treatment approach for transient cancer pain exacerbations. The main barriers to pain management are lack of standardized treatment methods for RCP, lack of knowledge related to RCP, and single drug dosage form. Doctors believe the most necessary measures to improve the current situation of poor cancer pain control include improving medical staff’s understanding and treatment techniques for RCP, updating treatment techniques and methods, and improving the configuration of drug types in medical institutions. Clinicians expect to improve understanding and treatment techniques through systematic training.Conclusion: Despite multiple available analgesic measures, the treatment of RCP remains challenging. Improving the understanding of medical staff towards RCP, improving treatment techniques, and increasing the accessibility of multiple drug types are important ways to improve the satisfaction of cancer pain management in the future.Keywords: refractory cancer pain, breakthrough cancer pain, pain management, opioid drugs

Yi He,1,2 Lejia Zhang,1,2 Siyuan Huang,1,2 Yuquan Tang,3 Yiming Li,1,2 Hongyu Li,1,2 Guanhui Chen,4 Xun Chen,1,2 Xiliu Zhang,1,2 Wei Zhao,1,2 Feilong Deng,1,2 Dongsheng Yu1,2 1Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, GuangZhou, 510080, People’s Republic of China; 3Zhujiang Hospital, Southern Medical University, Guangzhou, 510080, People’s Republic of China; 4Department of Stomatology, the Seventh Affiliated Hospital, Sun Yat-sen University, ShenZhen, 518107, People’s Republic of ChinaCorrespondence: Feilong Deng; Dongsheng Yu, Email dengfl@mail.sysu.edu.cn; yudsh@mail.sysu.edu.cnBackground: The ability of nanomaterials to induce osteogenic differentiation is limited, which seriously imped the repair of craniomaxillofacial bone defect. Magnetic graphene oxide (MGO) nanocomposites with the excellent physicochemical properties have great potential in bone tissue engineering. In this study, we aim to explore the craniomaxillofacial bone defect repairment effect of MGO nanocomposites and its underlying mechanism.Methods: The biocompatibility of MGO nanocomposites was verified by CCK8, live/dead staining and cytoskeleton staining. The function of MGO nanocomposites induced osteogenic differentiation of BMSCs was investigated by ALP activity detection, mineralized nodules staining, detection of osteogenic genes and proteins, and immune-histochemical staining. BMSCs with or without MGO osteogenic differentiation induction were collected and subjected to high-throughput circular ribonucleic acids (circRNAs) sequencing, and then crucial circRNA circAars was screened and identified. Bioinformatics analysis, Dual-luciferase reporter assay, RNA binding protein immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and osteogenic-related examinations were used to further explore the ability of circAars to participate in MGO nanocomposites regulation of osteogenic differentiation of BMSCs and its potential mechanism. Furthermore, critical-sized calvarial defects were constructed and were performed to verify the osteogenic differentiation induction effects and its potential mechanism induced by MGO nanocomposites.Results: We verify the good biocompatibility and osteogenic differentiation improvement effects of BMSCs mediated by MGO nanocomposites. Furthermore, a new circRNA-circAars, we find and identify, is obviously upregulated in BMSCs mediated by MGO nanocomposites. Silencing circAars could significantly decrease the osteogenic ability of MGO nanocomposites. The underlying mechanism involved circAars sponging miR-128-3p to regulate the expression of SMAD5, which played an important role in the repair craniomaxillofacial bone defects mediated by MGO nanocomposites.Conclusion: We found that MGO nanocomposites regulated osteogenic differentiation of BMSCs via the circAars/miR-128-3p/SMAD5 pathway, which provided a feasible and effective strategy for the treatment of craniomaxillofacial bone defects. Keywords: nanomaterials, MGO nanocomposites, craniomaxillofacial bone repair, circular RNAs, circAars