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Yunfei Luo,1,* Shaohua Sun,1,2,* Yuying Zhang,1,* Shuang Liu,1 Haixia Zeng,1 jin-E Li,1 Jiadian Huang,1 Lixuan Fang,1 Shiqi Yang,1 Peng Yu,1 Jianping Liu1,3,4 1Department of Endocrinology and Metabolism of the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330031, People’s Republic of China; 2Department of Metabolism and Endocrinology, XinSteel Center Hospital, Xinyu, Jiangxi, 338000, People’s Republic of China; 3Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang, Jiangxi, 330031, People’s Republic of China; 4Branch of National Clinical Research Center for Metabolic Diseases, Nanchang, Jiangxi, 330031, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianping Liu, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Nanchang, Jiangxi, 330031, People’s Republic of China, Email ndefy14105@ncu.edu.cnPurpose: Oltipraz has various applications, including for treating cancer, liver fibrosis, and cirrhosis. However, its role in regulating metabolic processes, inflammation, oxidative stress, and insulin resistance in STZ-induced T2DM remains unclear. Hence, a comprehensive understanding of how oltipraz ameliorates diabetes, particularly inflammation and oxidative stress, is imperative.Methods: The negative control (NC), T2DM model (T2DM), and T2DM models treated with oltipraz (OLTI) and metformin (MET) were constructed. The RNA sequencing (RNA-Seq) was performed on the pancreatic tissues. H&E staining was conducted on the liver and pancreatic tissues. The intraperitoneal glucose tolerance test (IPGTT), blood glucose and lipids, inflammatory factors, and oxidative stress indexes were measured. qPCR and Western blotting examined the nuclear factor erythroid-derived 2-like 2 (Nrf2)/ hemoglobin-1 (HO-1) signaling pathway, cell apoptosis-related genes, and Reg3g levels. Immunofluorescence (IF) analysis of the pancreas was performed to measure insulin secretion.Results: A total of 256 DEGs were identified in OLTI_vs_T2DM, and they were mainly enriched in circadian rhythm, cAMP, AMPK, insulin, and MAPK signaling pathways. Moreover, Reg3g exhibits reduced expression in T2DM_vs_NC, and elevated expression in OLTI_vs_T2DM, yet remains unchanged in MET_vs_T2DM. OLTI reduced fasting blood glucose and alleviated T2DM-induced weight loss. It improved blood glucose and insulin resistance, decreased blood lipid metabolism, reduced inflammation and oxidative stress through the Nrf2/HO-1 signaling pathway, mitigated pancreatic and liver tissue injury, and enhanced pancreatic β-cell insulin secretion. OLTI exhibited anti-apoptosis effects in T2DM. Moreover, OLTI exhibits superior antioxidant activity than metformin.Conclusion: In summary, OLTI improves blood glucose and insulin resistance, decreases blood lipid metabolism, reduces inflammation and apoptosis, suppresses oxidative stress through the Nrf2/HO-1 signaling pathway, mitigates pancreatic and liver tissue injury, and enhances pancreatic β-cell insulin secretion, thereby mitigating T2DM symptoms. Moreover, Reg3g could be an important target for OLTI treatment of T2DM.Keywords: Oltipraz, T2DM, oxidation stress, Nrf2, inflammation

Hong Zeng,1,2,* Xitong Geng,2,* Hao Wan,3,* Xiaoyu Qu,2 Shengwei Tang,2 Ruiyu Zhang,3 Minqin Zhou,2 Zichuan Yu,2 Jingying Pan,3 Hao Zheng,2 Yanting Zhu,2 Shuhan Huang,2 Da Huang1 1Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 2Second College of Clinical Medicine, Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China; 3First College of Clinical Medicine, Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Da Huang, Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, 1 minde Road, Nanchang, Jiangxi Province, 330000, People’s Republic of China, Email danmo0904@163.comBackground: The ubiquitin-proteasome system (UPS) is vital for protein quality control and its dysregulation is linked to diseases, including cancer. Targeting the UPS is becoming a promising approach in cancer therapy. However, the role of UPS modulation in thyroid carcinoma (THCA) remains to be fully elucidated.Methods: Initially, we utilized data from The Cancer Genome Atlas (TCGA) database to employ weighted gene co-expression network analysis (WGCNA) with LASSO regression to develop a prognostic model for core UPS genes implicated in THCA. Subsequently, we stratified the THCA training set into two distinct subtypes based on ubiquitin-proteasome system prognostic model score (UPS-PMS) characteristics. Key genes within the model were then subjected to functional analysis, immunotherapy evaluation, and drug sensitivity studies.Results: We delineated a prognostic model of the UPS comprising six genes, which we subsequently demonstrated was capable of forecasting patient prognosis. Moreover, our findings indicated a substantial correlation between UPS-PMS and immune microenvironmental factors, notably a negative correlation with myeloid immune cells and a potential influence on the Th1 to Th2 cells ratio. Especially, we observed a significant association between high UPS-PMS and an immunosuppressive microenvironment. Then, we elucidated the biological distinctions among various THCA sample subtypes, highlighting that the cluster_1 subtype is associated with an unfavorable prognosis. Of note, KCNA1 was identified as a pivotal prognostic gene within the UPS-PMS framework. We constructed a three-tiered regulatory network centered on KCNA1-related competing endogenous RNA (ceRNA). Furthermore, our results suggested that KCNA1 has potential as a target for immunotherapeutic strategies. Concurrently, drug sensitivity analyses demonstrated that high KCNA1 expression promoted gemcitabine resistance in patients, while KCNA1 knockdown increased sensitivity to gemcitabine.Conclusion: In conclusion, we developed a novel UPS-based prognostic model for THCA, identified key gene KCNA1, and assessed immunotherapy and drug sensitivity, revealing new therapeutic targets.Keywords: ubiquitin-proteasome system, thyroid carcinoma, prognostic model, immune microenvironment, drug sensitivity

Guansheng Zeng,1,* Jian Xu,1,* Huadong Zeng,1 Cuilan Wang,1 Lichang Chen,2 Huapeng Yu1 1Department of Pulmonary and Critical Care Medicine, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huapeng Yu, Department of Pulmonary and Critical Care Medicine, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China, Email huapengyu1960@163.com Lichang Chen, Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China, Email 519744491@qq.comPurpose: To investigate the differential clinical significance of fractional concentration of exhaled nitric oxide measured at a flow rate of 200 mL/s (FENO200) and concentration of nitric oxide in alveolar (CANO) in asthma, chronic obstructive pulmonary disease (COPD) or asthma-COPD Overlap (ACO).Methods: A total of 178 patients were included, with 82 patients in asthma group, 47 patients in COPD group and 49 patients in ACO group. Data for demographic data, spirometry and exhaled nitric oxide were collected for comparative analysis, correlation analysis and discriminant canonical analysis.Results: The values of FENO200 in asthma, COPD and ACO groups were 11.0(7.0– 22.3), 8.0(6.0– 11.0) and 9.0(6.5– 19.5) ppb, respectively. In the asthma group, FENO200 exhibited negative correlations with FEV1/FVC, MMEF and MEF50. No significant correlation was observed between CANO and pulmonary function parameters. In the COPD group, both FENO200 and CANO showed negative correlation with pulmonary function parameters including FVC, FEV1, PEF, MMEF, MEF75, MEF50. In the ACO group, FENO200 demonstrated no significant correlation with pulmonary function parameters, while CANO was correlated with FEV1, PEF, MMEF and MEF50. In COPD group, ΔFEV1 in the bronchodilator test was correlated with FENO200. As for the ACO group, ΔFEV1 was correlated with CANO. In the discriminant canonical analysis, four parameters including gender, age, MEF75 and FENO50 discriminated between the three groups of asthma, COPD and ACO.Conclusion: In asthma, COPD and ACO, FENO200 has demonstrated a robust correlation with CANO. Elevated FENO200 levels are predominantly indicative of pulmonary function impairment in asthma and COPD, whereas elevated CANO levels are mainly correlated with pulmonary function impairment in COPD and ACO. Compared with FENO200 and CANO, FENO50 may have a better discriminatory ability in distinguishing asthma, COPD and ACO.Keywords: FENO200, CANO, ACO, asthma, chronic obstructive pulmonary disease

Hui Zeng,1,* Rong Liu,1,2,* Chuanli Cheng,2,* Nana Yang,2 Luwen Luo,1,2 Shengshuang Long,3 Renjia Zhou,4 Kai Yan,1 Huantao Huang1 1Nursing Department of the Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 2School of Nursing of Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 3Infection Department of the Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 4ICU of the Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Zeng, Email zenghui.1221@163.comObjective: This study investigated the distribution and resistance patterns of pathogens in the intensive care unit of a newly established hospital in Guizhou Province to promote the rational use of antibiotics to reduce multidrug resistance.Methods: A retrospective analysis was conducted on the distribution of pathogens and changes in drug resistance in the ICU of a newly built hospital in Guizhou Province from March 2019 to December 2023. WHONET 5.6 was used to analyze the results.Results: A total of 2444 culture samples were received, predominantly sputum (34.66%) and blood (23.36%) samples, with a steady annual increase in specimen types. A total of 572 pathogenic strains were isolated, predominantly from respiratory specimens (54.02%), including 345 Gram-negative bacteria (60.31%), 135 Gram-positive cocci (23.60%), and 92 fungi (16.08%). The most frequent pathogens included Acinetobacter baumannii (30.77%), Candida albicans (11.71%), and Klebsiella pneumoniae (9.97%). Drug sensitivity tests indicated a fluctuating resistance rate of Acinetobacter baumannii over the past five years. Staphylococcus aureus displayed strong in vitro activity against vancomycin, tigecycline, and linezolid, with no resistant strains identified. The detection rates of carbapenem-resistant Acinetobacter baumannii (CR-AB), carbapenem-resistant Pseudomonas aeruginosa (CR-PA), methicillin-resistant Staphylococcus aureus (MRSA), and strains producing extended-spectrum beta-lactamases (ESBL) were 86.78%, 26.79%, 32.45%, 70.27%, and 23.54%, respectively.Conclusion: Compared with other countries in the world, China has increased its data on the prevalence of MDR pathogens and antibiotic resistance.The high resistance rate of Acinetobacter baumannii in the ICU underscores the need for effective infection control measures. Enhanced monitoring of CR-AB, ESBL-producing bacteria, and MRSA is essential, along with improved management of antibacterial drugs and the pursuit of new therapeutic options.Keywords: new-built hospital, intensive care unit, pathogens, multidrug-resistant bacteria, antimicrobial resistance

Xinqiang Liu,1,* Hongguang Ding,2,* Miner Chen,1,* Xusheng Li,2 Yan Xiao,1 Yongli Han,1 Hongke Zeng1 1Department of Intensive Care Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510800, People’s Republic of China; 2Department of Emergency Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510800, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongke Zeng, Department of Intensive Care Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, No. 106, Zhongshan 2nd Road, Guangzhou, People’s Republic of China, 510080, Tel/Fax +8602083827812-60810, Email zenghongke@gdph.org.cnBackground: Shenfu injection (SF) has demonstrated its potential to enhance cellular immunity and induce clinical regression in patients suffering from sepsis or infectious shock. However, the therapeutic effect of SF on sepsis-induced cognitive dysfunction (SAE) and the mechanisms involved are still unclear. We aimed to investigate the mechanism of SF in mice with SAE.Methods: Sepsis was constructed by caecal ligation and puncture. Mice were injected intraperitoneally with SF or NLRP3 inhibitor. The hippocampus injury of brain tissues was evaluated, and the levels of inflammatory cytokines (IL-1β, IL-18) and NLRP3 and Caspase 1 were measured. The active ingredients of SF were analyzed using network pharmacology, and molecular docking of the active ingredients of SF with NLRP3 and Caspase 1 was performed. BV-2 cells were treated with LPS or norcoclaurine. CCK-8 detected the cell viability, and the levels of inflammatory cytokines and NLRP3 and Caspase 1 were measured.Results: SF and NLRP3 inhibitor increased survival rate and the number of crossing the platform and decreased the escape latency time of sepsis mice. Moreover, SF and NLRP3 inhibitor improved neuronal damage and apoptosis in hippocampus of sepsis mice. In addition, SF and NLRP3 inhibitor reduced the levels of inflammatory cytokines, as well as inflammasomes in sepsis mice. There were 43 active ingredients in SF. Among them, 22 were Renshen and 21 were Fuzi. Renshen and Fuzi, the main active components of SF, form a complex regulatory network with NLRP3 and Caspase 1. (R)-norcoclaurine was most closely bound to NLRP3 with binding energy of − 7.2 kJ·mol− 1, ignavine was most closely bound to Caspase 1 with binding energy of − 8.3 kJ·mol− 1. Norcoclaurine increased the cell viability and decreased inflammation and pyroptosis.Conclusion: SF regulated NLRP3/Caspase 1 through (R)-norcoclaurinee to prevent SAE.Keywords: shenfu injection, NLRP3, caspase 1, pyroptosis, sepsis-associated encephalopathy

Yawan Jing,1,2 Ruixin Cheng,3 Hao Zeng,1 Qin Huang,1 Dongyu He,1 Jiayi Sun,1 Panwen Tian,1,4 Yalun Li1,4 1Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Institute of Respiratory Health and Multimorbidity, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, Precision Medicine Center/Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Gerontology and Geriatrics, Tibet Autonomous Region People’s Hospital, Lhasa, Tibet Autonomous Region, People’s Republic of China; 3Department of Radiation Oncology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, 510080, People’s Republic of China; 4Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Yalun Li; Panwen Tian, Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel/Fax +86 28 85423660, Email lunlunhx@qq.com; mrascend@163.comBackground: KRAS mutation is one of the most common driver oncogenes in non-small cell lung cancer (NSCLC), and the most common mutation subtype is G12C. However, there is still a lack of efficacy and prognosis data related to immunotherapy, which hinders the promotion of new strategies.Methods: Clinical characteristics and treatment outcomes were collected and analyzed for patients with NSCLC harboring KRAS mutations at West China Hospital of Sichuan University from June 2013 to March 2023.Results: Among the 231 patients with KRAS-mutated NSCLC, 29.4% had KRAS G12C mutations. Compared to the KRAS non-G12C NSCLC group, the KRAS G12C NSCLC group had a greater number of pack-years. The programmed death ligand 1 expression and the proportion of patients with a high tumor mutational burden were not significantly different between the two groups. Similar patterns of TP53, STK11, and CDKN2A mutations were observed between KRAS G12C and KRAS non-G12C NSCLC groups. The median progression-free survival (PFS) (8.4 vs 7.0 months, p=0.100) and overall survival (OS) (12.1 vs 18.1 months, p=0.590) were not statistically different between KRAS G12C and KRAS non-G12C. Compared to patients with KRAS G12C NSCLC who did not receive immunotherapy, patients who received immunotherapy had a better objective response rate (46.2% vs 0%, p=0.002), PFS (12.2 vs 7.5 months, p=0.087) and OS (49.9 vs 11.1 months, p=0.12).Conclusion: Patients with KRAS G12C were more likely to be smokers. Advanced KRAS G12C NSCLC patients who received immunotherapy had a better ORR than those who did not, suggesting that patients with G12C mutations are more likely to benefit from immunotherapy.Keywords: non-small cell lung cancer, KRAS G12C mutation, KRAS mutation, immunotherapy, overall survival

Weibei Sheng,1 Yaohang Yue,1 Tiantian Qi,1 Haotian Qin,1 Peng Liu,1 Deli Wang,1 Hui Zeng,2 Fei Yu1 1Department of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, 518036, People’s Republic of China; 2Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, People’s Republic of ChinaCorrespondence: Hui Zeng; Fei Yu, Email zenghui_36@163.com; oscarfyu@163.comAbstract: Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the degradation of joint cartilage, subchondral bone sclerosis, synovitis, and structural changes in the joint. Recent research has highlighted the role of various genes in the pathogenesis and progression of OA, with nuclear factor erythroid 2-related factor 2 (NRF2) emerging as a critical player. NRF2, a vital transcription factor, plays a key role in regulating the OA microenvironment and slowing the disease’s progression. It modulates the expression of several antioxidant enzymes, such as Heme oxygenase-1 (HO-1) and NAD(P)H oxidoreductase 1 (NQO1), among others, which help reduce oxidative stress. Furthermore, NRF2 inhibits the nuclear factor kappa-B (NF-κB) signaling pathway, thereby decreasing inflammation, joint pain, and the breakdown of cartilage extracellular matrix, while also mitigating cell aging and death. This review discusses NRF2’s impact on oxidative stress, inflammation, cell aging, and various cell death modes (such as apoptosis, necroptosis, and ferroptosis) in OA-affected chondrocytes. The role of NRF2 in OA macrophages, and synovial fibroblasts was also discussed. It also covers NRF2’s role in preserving the cartilage extracellular matrix and alleviating joint pain. The purpose of this review is to provide a comprehensive understanding of NRF2’s protective mechanisms in OA, highlighting its potential as a therapeutic target and underscoring its significance in the development of novel treatment strategies for OA.Keywords: nuclear factor erythroid 2-related factor 2, osteoarthritis, chondrocytes, inflammation, oxidative stress

Huamin Zeng,1 Yiran Zhang,1,2 Ningyi Liu,1,3 Qingqing Wei,1,3 Fan Yang,1 Jie Li4 1Cancer Prevention and Treatment Institute of Chengdu, Department of Pathology, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, Sichuan, 611130, People’s Republic of China; 2School of Medical and Life Sciences, Chengdu University of traditional Chinese Medicine, Chengdu, Sichuan, 611137, People’s Republic of China; 3School of Basic Medicine, North Sichuan Medical College, Nanchong, Sichuan, 637007, People’s Republic of China; 4Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, People’s Republic of ChinaCorrespondence: Jie Li, Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, People’s Republic of China, Tel +86 183 0831 2997, Email kerald2lj@126.com Fan Yang, Cancer Prevention and Treatment Institute of Chengdu, Department of Pathology, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, Sichuan, 611130, People’s Republic of China, Tel +86 136 7819 2175, Email yangfan03@126.comAbstract: Introduction of exogenous genes into target cells to overcome various tumor diseases caused by genetic defects or abnormalities and gene therapy, a new treatment method, provides a promising strategy for tumor treatment. Over the past decade, gene therapy has made exciting progress; however, it still faces the challenge of low nucleic acid delivery and release efficiencies. The emergence of nonviral vectors, primarily nanodelivery and release systems (NDRS), has resulted in a historic breakthrough in the application of gene therapy. NDRS, especially stimulus-responsive NDRS that can respond in a timely manner to changes in the internal and external microenvironment (eg, low pH, high concentration of glutathione/reactive oxygen species, overexpressed enzymes, temperature, light, ultrasound, and magnetic field), has shown excellent loading and release advantages in the precision and efficiency of tumor gene therapy and has been widely applied. The only disadvantage is that poor transfection efficiency limits the in-depth application of gene therapy in clinical practice, owing to the presence of biological barriers in the body. Therefore, this review first introduces the development history of gene therapy, the current obstacles faced by gene delivery, strategies to overcome these obstacles, and conventional vectors, and then focuses on the latest research progress in various stimulus-responsive NDRS for improving gene delivery efficiency. Finally, the future challenges and prospects that stimulus-responsive NDRS may face in clinical application and transformation are discussed to provide references for enhancing in-depth research on tumor gene therapy.Keywords: stimulus-responsive NDRS, gene delivery, tumor treatment, delivery and release efficiency, tumor microenvironment, physiological barrier, efficacy improvement strategies

Siyang Cao,1– 3,* Yihao Wei,1– 3,* Yaohang Yue,1– 3,* Deli Wang,1– 3 Ao Xiong,1– 3 Hui Zeng1– 3 1National & Local Joint Engineering Research Centre of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China; 3Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ao Xiong; Hui Zeng, Email xiongao@189.cn; zenghui@pkuszh.comPurpose: Over the past 24 years, significant advancements have been made in applying artificial intelligence (AI) to musculoskeletal (MSK) diseases. However, there is a lack of analytical and descriptive investigations on the trajectory, essential research directions, current research scenario, pivotal focuses, and future perspectives. This research aims to provide a thorough update on the progress in AI for MSK diseases over the last 24 years.Methods: Data from the Web of Science database, covering January 1, 2000, to March 1, 2024, was analyzed. Using advanced analytical tools, we conducted comprehensive scientometric and visual analyses.Results: The findings highlight the predominant influence of the USA, which accounts for 28.53% of the total publications and plays a key role in shaping research in this field. Notable productivity was seen at institutions such as the University of California, San Francisco, Harvard Medical School, and Seoul National University. Valentina Pedoia is identified as the most prolific contributor. Scientific Reports had the highest number of publications in this area. The five most significant diseases are joint diseases, bone fractures, bone tumors, cartilage diseases, and spondylitis.Conclusion: This comprehensive scientometric assessment benefits both experienced researchers and newcomers, providing quick access to essential information and fostering the development of innovative concepts in this field. Keywords: artificial intelligence, musculoskeletal diseases, scientometrics, data visualization, global scientific frontiers

Ziwei Huang,1 Shanli Zhang,1 Zehui Qin,1 Gaoxiang Ai,1 Minhua Li,1 Shiting Gong,1 Yuhong Liu,1 Huifang Zeng,2 Jiannan Chen,1 Ziren Su,1 Zhengquan Lai3 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 2The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Department of Pharmacy, Shenzhen University General Hospital/Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Zhengquan Lai, Department of Pharmacy, Shenzhen University General Hospital/Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China, Email cruise0303@163.com Ziren Su, School of pharmaceutical sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China, Email suziren@gzucm.edu.cnPropose: Oxyberberine (OBB), one of the main metabolites of berberine derived from intestinal and erythrocyte metabolism, exhibits appreciable anti-hyperuricemic activity. However, the low water solubility and poor plasma concentration–effect relationship of OBB hamper its development and utilization. Therefore, an OBB-hydroxypropyl-β-cyclodextrin (HP-β-CD) supersaturated drug delivery system (SDDS) was prepared and characterized in this work.Methods: OBB-HP-β-CD SDDS was prepared using the ultrasonic-solvent evaporation method and characterized. Additionally, the in vitro and in vivo release experiments were conducted to assess the release kinetics of OBB-HP-β-CD SDDS. Subsequently, the therapeutic efficacy of OBB-HP-β-CD SDDS on hyperuricemia (HUA) was investigated by means of histopathological examination and evaluation of relevant biomarkers.Results: The results of FT-IR, DSC, PXRD, NMR and molecular modeling showed that the crystallized form of OBB was transformed into an amorphous OBB-HP-β-CD complex. Dynamic light scattering indicated that this system was relatively stable and maintained by formation of nanoaggregates with an average diameter of 23 nm. The dissolution rate of OBB-HP-β-CD SDDS was about 5 times higher than that of OBB raw material. Furthermore, the AUC0-t of OBB-HP-β-CD SDDS (10.882 μg/mL*h) was significantly higher than that of the raw OBB counterpart (0.701 μg/mL*h). The oral relative bioavailability of OBB-HP-β-CD SDDS was also enhanced by 16 times compared to that of the raw material. Finally, in vivo pharmacodynamic assay showed the anti-hyperuricemic potency of OBB-HP-β-CD SDDS was approximately 5– 10 times higher than that of OBB raw material.Conclusion: Based on our findings above, OBB-HP-β-CD SDDS proved to be an excellent drug delivery system for increasing the solubility, dissolution, bioavailability, and anti-hyperuricemic potency of OBB. Keywords: oxyberberine, cyclodextrin, supersaturated drug delivery systems, pharmacokinetics, hyperuricemia

Yanshijing Zhou,1 Zihui Yang,2 Hong Zeng2 1Department of Plastic and Cosmetic Surgery, Maternal and Child Health Hospital of Hubei Province, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Plastic and Cosmetic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Zihui Yang; Hong Zeng, Department of Plastic and Cosmetic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China, Email yzh_2017@hust.edu.cn; zenghong1109@163.comPurpose: Emerging evidence demonstrates the vital role of aging and long non-coding RNAs (lncRNAs) in breast cancer (BC) progression. Our study intended to develop a prognostic risk model based on aging-related lncRNAs (AG-lncs) to foresee BC patients’ outcomes.Patients and Methods: 307 aging-related genes (AGs) were sequenced from the TCGA project. Then, 697 AG-lncs were identified by the co-expression analysis with AGs. Using multivariate and univariate Cox regression analysis, and LASSO, 6 AG-lncs, including al136531.1, mapt-as1, al451085.2, otud6b-as1, tnfrsf14-as1, and linc01871, were validated to compute the risk score and establish a risk signature. Expression levels of al136531.1, mapt-as1, al451085.2, tnfrsf14-as1, and linc01871 were higher in low-risk BC patients, whereas otud6b-as1 expression was higher in high-risk BC patients. In the training and testing set, high-risk patients performed shorter PFI, OS, and DFS than low-risk patients.Results: Our risk signature had the highest concordance index among other established prognostic signatures and displayed ideal predictive ability for 1-, 3- and 5-year patient OS in the nomogram. Additionally, BC patients with different risk score levels showed different immune statuses and responses to immunotherapy via GSEA, ssGSEA, ESTIMATE algorithm, and TIDE algorithm analysis. Of note, the qRT-PCR analysis validated that these 6 AG-lncs expressed quite differentially in BC tissues at various clinical stages.Conclusion: The risk signature of 6 AG-lncs might offer a novel prognostic biomarker and promisingly enhance BC immunotherapy’s effectiveness.Keywords: risk model, senescence, immune, cancer therapy

Yiyang Gong,1,2,* Minqin Zhou,2,* Yanting Zhu,2,* Jingying Pan,2 Xuanrui Zhou,2 Yike Jiang,2 Hong Zeng,2 Hao Zheng,2 Xitong Geng,2 Da Huang1 1Department of Thyroid Surgery; Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Second College of Clinical Medicine, Nanchang University, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Da Huang, Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, Jiangxi Province, 330000, People’s Republic of China, Tel +13576113993, Email danmo0904@163.comPurpose: Hepatocellular carcinoma is the most common primary liver cancer, with poor prognosis. Complex immune microenvironment of the liver is linked to the development of HCC. PVALB is a calcium-binding protein which has been described as a cancer suppressor gene in thyroid cancer and glioma. Nevertheless, the role of PVALB in HCC is unknown.Materials and Methods: We obtained data from TCGA and GSE54236 datasets. MCP-counter, WGCNA and LASSO model were applied to identify PVALB. With UALCAN, MethSurv, and other websites, we probed the expression, methylation and survival of PVALB. LinkedOmics and GSEA were adopted for functional analysis, while TIMER, TISIDB, Kaplan-Meier plotter, TIDE databases were utilized to evaluate the relevance of PVALB to the tumor immune microenvironment and predict immunotherapy efficacy. TargetScan, DIANA, LncRNASNP2 databases and relevant experiments were employed to construct ceRNA network. Finally, molecular docking and drug sensitivity of PVALB were characterized by GeneMANIA, CTD, and so on.Results: PVALB was recognized as a gene associated with HCC and NK cell. Its expression was down-regulated in HCC tissue, which lead to adverse prognosis. Besides, the hypomethylation of PVALB was related to its reduced expression. Notably, PVALB was tightly linked to immune, and its reduced expression attenuated the anticancer effect of NK cells via the Fas/FasL pathway, leading to a adverse outcome. The lnc-YY1AP1-3/hsa-miR-6735-5p/PVALB axis may regulate the PVALB expression. Finally, we found immunotherapy might be a viable treatment option.Conclusion: In a word, PVALB is a prognostic indicator, whose low expression facilitates HCC progression by impacting NK cell infiltration.Keywords: PVALB, hepatocellular carcinoma, immune, ceRNA, bioinformatics, prognostic factor

Siyang Cao,1– 3,* Yihao Wei,1– 3,* Yaohang Yue,1– 3,* Ao Xiong,1– 3 Hui Zeng1– 3 1National & Local Joint Engineering Research Centre of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China; 3Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ao Xiong; Hui Zeng, Peking University Shenzhen Hospital, No. 1120 Lianhua Road, Futian District, Shenzhen, Guangdong Province, People’s Republic of China, Tel/Fax +86 755 8392 3333, Email xiongao@189.cn; zenghui@pkuszh.comAbstract: During the past decade, mounting evidence has increasingly linked programmed cell death (PCD) to the progression and development of osteoarthritis (OA). There is a significant need for a thorough scientometric analysis that recapitulates the relationship between PCD and OA. This study aimed to collect articles and reviews focusing on PCD in OA, extracting data from January 1st, 2013, to October 31st, 2023, using the Web of Science. Various tools, including VOSviewer, CiteSpace, Pajek, Scimago Graphica, and the R package, were employed for scientometric and visualization analyses. Notably, China, the USA, and South Korea emerged as major contributors, collectively responsible for more than 85% of published papers and significantly influencing research in this field. Among different institutions, Shanghai Jiao Tong University, Xi’an Jiao Tong University, and Zhejiang University exhibited the highest productivity. Prolific authors included Wang Wei, Wang Jing, and Zhang Li. Osteoarthritis and Cartilage had the most publications in this area. Keywords related to PCD in OA prominently highlighted ‘chondrocytes’, ‘inflammation’, and ‘oxidative stress’, recognized as pivotal mechanisms contributing to PCD within OA. This study presents the first comprehensive scientometric analysis, offering a broad perspective on the knowledge framework and evolving patterns concerning PCD in relation to OA over the last decade. Such insights can aid researchers in comprehensively understanding this field and provide valuable directions for future explorations. Keywords: global scientific frontiers, programmed cell death, osteoarthritis, scientometrics, visualization analysis

Xiaoling Long,1,* Huan Zeng,1,* Yun Zhang,1 Qiulong Lu,1 Zhao Cao,2 Hong Shu1 1Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Shu, Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, No. 71 Hedi Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86 7715640296, Email shuhong@gxmu.edu.cn Zhao Cao, Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86 7715356724, Email river_79@126.comPurpose: Developing a high-value, convenient, and validated differential diagnosis model to differentiate alpha-fetoprotein (AFP) negative hepatic occupying lesions and assist clinicians in early identification and intervention.Patients and Methods: A total of 340 patients with AFP-negative hepatic occupying lesions who were admitted to the Guangxi Medical University Cancer Hospital between August 2021 and April 2023 were included in the final retrospective analysis. The data were randomly divided into training and validation sets in a 7:3 ratio after performing multiple interpolations. In the training set, laboratory variables and models were screened using least absolute shrinkage and selection operator regression analysis, comparison of five machine learning algorithms, and univariate, as well as multivariate logistic regression analysis. A diagnostic prediction nomogram model was developed. We evaluated and validated the model using the receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis (DCA).Results: We identified six significant predictive factors from the results of multivariate logistic analysis in the training set and incorporated them into the nomogram model for diagnosing AFP-negative hepatic malignant occupying lesions (HMOL). The diagnostic nomogram, including gender, age, des-gamma-carboxy prothrombin (DCP), serum ferritin (SF), AFP, and hepatitis B surface antigen (HBsAg), achieved an area under the curve of 0.905 discriminated patients with HMOL from those with benign occupying lesions. Additionally, calibration curves demonstrated the close alignment between the nomogram predictions and the ideal curve, along with the consistency between predictions and actual results. Moreover, the DCA curves illustrated indicated benefit for all patients. These finding were confirmed by the validation set.Conclusion: The GADSAH model specifically targets the discrimination of malignant and benign liver lesions in AFP-negative patients. It offers a noninvasive, cost-effective, and efficient approach for diagnosing such cases.Keywords: hepatic occupying lesions, alpha-fetoprotein-negative, nomogram, diagnostic model

Yuying Zhou,1,* Wu Xue,2,* Xinyu Meng,2,* Adheesh Bhandari,2,3,* Hanqian Zeng,4 Rajan KC,5 Suzita Hirachan,6 Erjie Xia2 1Department of Oncology and Hematology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Surgery, Breast and Thyroid Unit, Primera Hospital, Kathmandu, Nepal; 4Department of Surgical Oncology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang Province, People’s Republic of China; 5Central Department of Zoology, Tribhuvan University, Kirtipur, Kathmandu, Nepal; 6Department of General Surgery, Breast and Thyroid Unit, Tribhuvan University, Teaching Hospital, Kathmandu, Nepal*These authors contributed equally to this workCorrespondence: Erjie Xia, Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Tel +86 577 5557 8527, Email erjiexia1@126.com Yuying Zhou, Department of Oncology and Hematology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, Zhejiang, People’s Republic of China, Tel +8615757194239, Email yuying_ne@163.comBackground: Breast cancer (BC) is increasingly becoming the primary reason for death in women, which sounded the alarm. Thus, finding a novel management target for BC is imminent.Materials and Methods: The data on gene expression and clinicopathological characteristics were downloaded from The Cancer Genome Atlas (TCGA). The expression of GNPNAT1 in 40 paired breast cancer and adjacent tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Univariate and Multivariate logistic regression methodology was applied to analyze the prognostic factors for lymph node metastasis (LNM). Based on the status of breast cancer-relative receptors, patients were distributed into six groups, and then the Kaplan-Meier survival analysis with a Log rank test was applied to investigate the involvement among the expression of GNPNAT1 and overall survival (OS).Results: We found higher expression of GNPNAT1 was connected with poor survival in breast cancer by COX regulation analysis. GO, KEGG, and GSEA analysis prompted that GNPNAT1 was connected with the defense mechanism of cells, cell proliferation, and division. Immunization infiltration analysis showed that high GNPNAT1 was negatively connected with 16 immunization infiltration cell types and positively connected with four immunization infiltration cell types.Conclusion: As a whole, our results indicated that GNPNAT1 might be a probable biomarker for diagnosis and prognosis in breast cancer.Keywords: GNPNAT1, biomarker, breast cancer, diagnosis, prognosis

Dongning Lyu, Guangyu He, Kan Zhou, Jin Xu, Haifei Zeng, Tongyu Li, Ningbo Tang Department of Nephrology Clinic, Guangxi International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Dongning Lyu, Guangxi International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine, No. 8 Qiuyue Road, Liangqing District, Nanning, Guangxi, 530200, People’s Republic of China, Tel +8613377191933, Email tsj757700@163.comPurpose: Uremia, which is characterized by immunodeficiency, is associated with the deterioration of kidney function. Immune-related genes (IRGs) are crucial for uremia progression.Methods: The co-expression network was constructed to identify key modular genes associated with uremia. IRGs were intersected with differentially expressed genes (DEGs) between uremia and control groups and key modular genes to obtain differentially expressed IRGs (DEIRGs). DEIRGs were subjected to functional enrichment analysis. The protein-protein interaction (PPI) network was constructed. The candidate genes were identified using the cytoHubba tool. The biomarkers were identified using various machine learning algorithms. The diagnostic value of the biomarkers was evaluated using receiver operating characteristic (ROC) analysis. The immune infiltration analysis was implemented. The biological pathways of biomarkers were identified using gene set enrichment analysis and ingenuity pathway analysis. The mRNA expression of biomarkers was validated using blood samples of patients with uremia and healthy subjects with quantitative real-time polymerase chain reaction (qRT-PCR).Results: In total, four biomarkers (PDCD1, NGF, PDGFRB, and ZAP70) were identified by machine learning methods. ROC analysis demonstrated that the area under the curve values of individual biomarkers were > 0.9, indicating good diagnostic power. The nomogram model of biomarkers exhibited good predictive power. The proportions of six immune cells significantly varied between the uremia and control groups. ZAP70 expression was positively correlated with the proportions of resting natural killer (NK) cells, naïve B cells, and regulatory T cells. Functional enrichment analysis revealed that the biomarkers were mainly associated with translational function and neuroactive ligand-receptor interaction. ZAP70 regulated NK cell signaling. The PDCD1 and NGF expression levels determined using qRT-PCR were consistent with those determined using bioinformatics analysis.Conclusion: PDCD1, NGF, PDGFRB, and ZAP70 were identified as biomarkers for uremia, providing a theoretical foundation for uremia diagnosis. Keywords: differential expression analysis, WGCNA, immune infiltration, nomogram, diagnosis

Teng Long,1,2,* Zhoutian Yang,1,2,* Huilan Zeng,1,2,* Weijie Wu,1,2 Zhiwen Hu,1,2 Zhenyun Yang,1,2 Dandan Hu,1,2 Zhongguo Zhou,1,2 Minshan Chen,1,2 Yaojun Zhang1,2 1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Minshan Chen; Yaojun Zhang, Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Dongfeng East Road 651, Guangzhou, Guangdong, 510000, People’s Republic of China, Tel +86-20-87343828, Fax +86-20-87343585, Email chenmsh@sysucc.org.cn; zhangyuj@sysucc.org.cnPurpose: To compare the treatment efficacy and safety of transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and programmed cell death protein-1 (PD-1) inhibitors for patients with unresectable hepatocellular carcinoma (HCC).Patients and Methods: 81 unresectable HCC patients were retrospectively analyzed, including 30 or 51 patients treated with either TKIs and PD-1 inhibitors combined with TACE (TTP) or HAIC (HTP), respectively. Tumor response and survival outcomes were compared.Results: The median overall survival (mOS) was 21.0 months in the TTP group and 15.0 months in the HTP group (P = 0.525; HR = 1.23; 95% CI 0.66– 2.29). The median progression-free survival (mPFS) was 6.7 months in the TTP group and 9.9 months in the HTP group (P = 0.160; HR = 0.70; 95% CI 0.42– 1.16). After Propensity Score Matching (PSM), the mOS was 21.0 months in the TTP group and 18.0 months in the HTP group (P = 0.644; HR = 1.20; 95% CI 0.56– 2.58). The mPFS was 6.4 months in the TTP group and 15.0 months in the HTP group (P = 0.028; HR = 0.49; 95% CI 0.26– 0.93). The disease control rate in overall response (90.2% vs 76.7%, P = 0.116, before PSM; 91.7% vs 75.0%, P = 0.121, after PSM) and intrahepatic response (94.1% vs 80.0%, P = 0.070, before PSM; 91.7% vs 79.2%, P = 0.220, after PSM) were higher in the HTP group than in the TTP group.Conclusion: Though including more advanced tumors, the clinical outcomes of HAIC combined with TKIs and PD-1 inhibitors are comparable to TACE-based combination therapy for unresectable HCC. Nevertheless, HTP significantly improved the PFS benefits in HCC patients with with large tumor burden or vascular invasion.Keywords: transarterial chemoembolization, hepatic arterial infusion chemotherapy, tyrosine kinase inhibitors, programmed cell death protein − 1, hepatocellular carcinoma

Tong Mo,1,* Wenxian Huang,2,* Weisheng Sun,1 Yan Hu,3 Leroy Mcdonald,4 Zhanqi Hu,3 Li Chen,3 Jianxiang Liao,3 Bruce Hermann,5 Vivek Prabhakaran,4– 6 Hongwu Zeng1,6 1Department of Radiology, Shenzhen Children’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Department of Pediatrics, Shenzhen Children’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 3Department of Neurology, Shenzhen Children’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 4Neurosciences Training Program, University of Wisconsin, Madison, WI, USA; 5Department of Neurology, University of Wisconsin, Madison, WI, USA; 6Department of Radiology, University of Wisconsin, Madison, WI, USA*These authors contributed equally to this workCorrespondence: Hongwu Zeng, Shenzhen, Guangdong, People’s Republic of China, Tel +86 18938691099, Email homerzeng@126.com Vivek Prabhakaran, Department of Radiology, University of Wisconsin, Madison, WI, USA, Tel +1 608 265 5269, Email VPrabhakaran@uwhealth.orgObjective: Neuropsychological evidence revealed language impairment in children with benign epilepsy with centrotemporal spikes (BECTS). This study investigates language function using task-activated fMRI.Methods: We conducted a language task fMRI study on three groups on a 3.0T MRI scanner, including a new onset drug naïve group (NODN-BECTS, n=11, age=9.6± 1.6), an established epilepsy with medication-treated group (Med-BECTS, n=17, age=10.7± 2.2) and a healthy control group (HC, n=18, age=10.8± 1.7). We use MATLAB14 and SPM12 to pre-process and analyze the data. A one-sample t-test was used to identify task-related brain activation changes in each group, based on the general linear model (GLM). And, then two sample t-test was performed to compare different activated regions between groups. In addition, scores on the most recent Mandarin school exams were acquired to examine and contrast extra-scanner language performance.Results: Statistical results show that some language-related brain regions (such as the left superior frontal gyrus and cerebellar vermis) were additionally activated in the NODN-BECTS group compared with the HC group. Compared with NODN-BECTS and HC groups, decreased activations were found in language-related regions in the Med-BECTS group, including the left insula, superior and middle frontal gyri, and bilateral middle occipital gyri. On the Mandarin school exams, the average score for HC was 87.3± 8.2, NODN was 84.8± 7.8, and Med was 78.2± 13.2. There was a trend toward statistical significance between the Med and the HC (p = 0.074) as well as NODN (p = 0.092) groups. No statistically significant differences were found between the HC and the NODN-BECTS groups.Significance: Language task fMRI reveals additional areas of activation in new onset BECTS compared to healthy controls which may be compensatory in nature. Antiseizure medications (ASMs) and/or longer duration of BECTS additionally appears to affect language-related regions and reduce their functional ability.Keywords: benign epilepsy with centrotemporal spikes, cognition, language impairment, functional magnetic resonance imaging

Jia Pan,1,* Bo Yang,1,* Zihang Wang,2 Lei Tang,1 Peng Jia,3,4 Shujuan Yang,1,2,4 Honglian Zeng1 1Department of Clinical Medical College & Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, People’s Republic of China; 2Department of West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of School of Resources and Environmental Sciences, Wuhan University, Wuhan, People’s Republic of China; 4Department of International Institute of Spatial Health Epidemiology (ISLE), Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shujuan Yang; Honglian Zeng, Email rekiny@126.com; zenghonglianhl@163.comAim: China has the highest rail transportation density in the world. Compared to other occupational populations, railway workers in China face increased risk of chronic non-communicable diseases. This study aims to investigate the relationship between the triglyceride-glucose (TyG) index and carotid artery plaque (CAP) in a population of railway workers in southwest China.Methods: The cross-sectional study was conducted among 3169 railway workers who were categorized into four groups based on TyG index quartiles. The presence of CAP was assessed using carotid Doppler ultrasound. Logistic regression and restricted cubic spline analyses were used to estimate the association between TyG index and CAP, and subgroup analyses were performed based on age, blood pressure, metabolic dysfunction-associated fatty liver disease (MAFLD), smoking, drinking, and physical activity.Results: Participants with higher TyG index quartiles had a higher prevalence of CAP, with 11.63%, 14.11%, 20.20%, and 18.56% from the first to fourth quartile, respectively. The multi-adjusted logistic regression models showed a positive association between TyG index and the risk of CAP (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.06– 1.41) when treated as a continuous variable. When analyzed as a categorical variable with increasing TyG index tertiles, the risk of CAP substantially increased with ORs (95% CIs) of 1.22 (0.90– 1.65) for the second quartile, 1.70 (1.27– 2.28) for the third quartile, and 1.46 (1.08– 1.98) for the fourth quartile compared to the lowest quartile. Restricted cubic spline revealed that the association gradually strengthened with the increase of the TyG index below 9.56.Conclusion: TyG index was significantly associated with CAP, notably in populations with elevated quartiles of TyG index among railway workers. Monitoring the TyG index could be a useful risk management strategy for CAP in occupation population.Keywords: TyG index, insulin resistance, carotid artery plaque, MAFLD, occupational population

Qing Su,1 Chen Jin,2 Yi Yang,1 Jingxian Wang,1 Juejin Wang,1 Hao Zeng,1 Yaqing Chen,1 Junxi Zhou,1 Yi Wang1 1Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Yi Wang, Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Chashan High Education Zone, Wenzhou, Zhejiang, 325035, People’s Republic of China, Tel +86-577-8669-9358, Email wang.yi@wmu.edu.cnPurpose: Observational studies have reported that autoimmune diseases are closely related to sarcopenia, but the causalities of autoimmune diseases with sarcopenia have not been established. We conducted this Mendelian randomization (MR) study to reveal the causal associations of overall autoimmune disease and five common autoimmune diseases with sarcopenia-related traits.Methods: The publicly available summary-level data of autoimmune diseases and three sarcopenia-related traits were used for analysis. The causal effects of autoimmune diseases on sarcopenia-related traits were first identified in discovery samples using the inverse-variance-weighted method as the primary method, and the robustness of results was examined by additional sensitivity analyses. Replication MR analyses were then conducted using replication samples of five autoimmune diseases. Finally, the possibility of reverse causation was assessed by reverse MR analyses.Results: In both the discovery and replication samples, we identified potential causal effects of rheumatoid arthritis (RA) on appendicular lean mass (ALM) and low grip strength (OR = 0.979, 95% CI: 0.964– 0.995 for ALM; OR = 1.042, 95% CI: 1.013– 1.072 for low grip strength), but not on walking pace. We also found that inflammatory bowel disease (IBD) and type 1 diabetes (T1D) were only causally negatively associated with ALM in the discovery stage (OR = 0.986, 95% CI: 0.974– 0.999 for IBD; OR = 0.987, 95% CI: 0.975– 0.999 for T1D), whereas systemic lupus erythematosus, multiple sclerosis, and overall autoimmune disease were not associated with any of the three sarcopenia-related traits. Additionally, reverse MR analysis only found an association between walking pace and overall autoimmune disease, but this association did not remain in the weighted-median method.Conclusion: This study demonstrates that RA is causally associated with low grip strength and reduced ALM, and that IBD and T1D may be causally negatively related to ALM.Keywords: Mendelian randomization, autoimmune disease, sarcopenia, rheumatoid arthritis, grip strength, appendicular lean mass

Han Li,1,&ast; Lu Guo,2,&ast; Ke Su,1,&ast; Changlun Li,3 Yi Jiang,1 Pan Wang,4 Jiali Chen,1 Zhenying Wu,1 Ke Xu,5 Tao Gu,1 Hao Zeng,1 Kun He,6 Hao Chi,1 Wenxi Zhao,7 Lei Han,3 Yunwei Han1 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China; 4Clinical Skills Center, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 5Department of Oncology, Chongqing General Hospital, Chongqing, 401147, People’s Republic of China; 6Clinical Research Institute, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 7Clinical Medical College, Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunwei Han, The Affiliated Hospital of Southwest Medical University, 25 TAIPING Street, Luzhou City, Sichuan Province, People’s Republic of China, Tel +86-830-3165598, Email Lanpaoxiansheng@126.com Lei Han, Department of Oncology, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China, Email hanleixxf@126.comBackground: TACE and TACE with or without targeted immunotherapy are crucial comprehensive therapies for middle and advanced HCC. However, a reasonable and concise score is needed to evaluate TACE and TACE combined with systemic therapy in HCC treatment.Methods: The HCC patients were grouped into two groups: training group (n = 778) (treated with TACE) and verification group (n = 333). The predictive value of baseline variables on overall survival was analyzed using COX model, and easy-to-use ALR (AST and Lym-R) scores. The best cut-off value of AST and Lym-R were determined using X-Tile software based on total survival time (OS) and further verified via a restricted three-spline method. Meanwhile, the score was further verified using two independent valid sets: TACE combined with targeted therapy and TACE with targeted combined immunotherapy.Results: In multivariate analysis, baseline serum AST> 57.1 (p < 0.001) and Lym-R≤ 21.7 (p < 0.001) were identified as independent prognostic factors. The OS of patients in the TACE pooled cohort with 0, 1, and 2 scores were 28.1 (95% CI 24– 33.8) months, 15 (95% CI 12.4– 18.6) months, and 7.4 (95% CI 5.7– 9.1) months, respectively. The time-varying ROC curve based on ALR showed that the AUC values for predicting 1, -2-and 3-year OS were 0.698, 0.718, and 0.636, respectively. These results are confirmed in two independent valid sets of TACE combined with targeted therapy and TACE with targeted combined immunotherapy. And we established a nomogram after COX regression to predict the 1 -, 2- and 3-year survival time.Conclusion: Our study confirmed that ALR score can predict the prognosis of HCC treated with TACE or TACE combined with systemic therapy.Keywords: TACE, immunotherapy, targeted therapy, nomogram

Yuhao Zeng,1,&ast; Sha Zhu,1,&ast; Zilin Wang,1 Junru Chen,1 Jindong Dai,1 Zhenhua Liu,1 Guangxi Sun,1 Jiayu Liang,1 Xingming Zhang,1 Zhipeng Wang,1 Jinge Zhao,1 Yuchao Ni,1 Jiyu Yang,1 Minghao Wang,1 Qiang Wei,1 Xiang Li,1 Ni Chen,2 Zhiping Li,3 Xin Wang,3 Yali Shen,3 Jin Yao,4 Rui Huang,5 Jiyan Liu,6 Diming Cai,7 Hao Zeng,1 Pengfei Shen1 1Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 5Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 6Department of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 7Department of Medical Ultrasound, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengfei Shen; Hao Zeng, Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Email cdhx510@163.com; kucaizeng@163.comPurpose: Multidisciplinary team (MDT) discussion is a widely used model to manage patients diagnosed with cancer. However, there has been no direct evidence to prove its effect on the prognosis of metastatic renal cell carcinoma (mRCC) patients, so this study explored the impact of MDT discussion on mRCC patient survival.Methods: The clinical data of 269 mRCC patients were retrospectively collected from 2012 to 2021. The cases were grouped into the MDT and non-MDT groups, then subgroup analysis was performed according to different histology types, as well as exploring the role of MDT in patients who have undergone multiple-line therapy. Overall survival (OS) and progression free survival (PFS) were set as the study endpoint.Results: Approximately half (48.0%, 129/269) of the patients were in the MDT group, with univariable survival analyses showing these patients had remarkably longer median OS (MDT group: 73.7 months; non-MDT group: 33.2 months, hazard ratio (HR): 0.423 (0.288, 0.622), p< 0.001) and longer median PFS (MDT group: 16.9 months, non-MDT group: 12.7 months, HR: 0.722 (0.542, 0.962), p=0.026). Furthermore, MDT management resulted in longer survival for both ccRCC and non-ccRCC subgroups. Patients in the MDT group were more likely to receive multi-line therapy (MDT group: 79/129, 61.2% vs non-MDT group: 56/140, 40.0%, p< 0.001), and within this patient group, MDT management still resulted in longer OS (MDT group: 94.0 months; non-MDT group: 43.5 months, p=0.009).Conclusion: MDT is associated with prolonged overall survival in mRCC independent of histology, ensuring that patients receive better management and precise treatment.Keywords: mRCC, MDT, overall survival, prognosis, ccRCC, non-ccRCC, multi-line treatment

Ke Su,1,&ast; Weihong Huang,2,&ast; Xueting Li,3,&ast; Ke Xu,4,&ast; Tao Gu,1 Yanlin Liu,1 Juan Song,2 Keyi Qian,5 Yaoyang Xu,2 Hao Zeng,1 Yipei Yang,6 Lu Guo,7 Yunwei Han1 1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Clinical Medical College, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Department of Oncology, 363 Hospital, Chengdu, 610041, People’s Republic of China; 4Department of Oncology, Chongqing General Hospital, Chongqing, 401147, People’s Republic of China; 5Department of Nursing, Sichuan University, Chengdu, 610065, People’s Republic of China; 6Department of Orthopedic Surgery, Shenzhen Hospital, Southern Medical University, Shenzhen, 518000, People’s Republic of China; 7Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunwei Han; Lu Guo, The Affiliated Hospital of Southwest Medical University, 25 TAIPING Street, Luzhou City, Sichuan Province, People’s Republic of China, Tel +86-830-3165598 ; +86-830-3165613, Email hanyunwei@swmu.edu.cn; guolu68@163.comBackground: Tumor proliferation is frequently accompanied by aberrant enzyme production. We aim to investigate the potential predictive value of both plasma alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in patients with HCC and to develop a nomogram to assess the prognosis of HCC.Methods: The trial involved 2327 patients between May 2015 and March 2022. Within 7 days of enrollment, the levels of ALP and LDH were measured, and their association with survival was assessed. And we had developed and validated a new nomogram based on ALD and ALP.Results: Using X-tile software, the optimal cut-off values were determined to be ALP = 172 U/L and LDH = 241 U/L. The high ALP (≥ 172), LDH (≥ 241), and ALP/LDH (≥ 0.91) groups had lower median overall survival (mOS) than low ALP (< 172), LDH (< 241), and ALP/LDH (< 0.91) groups (all p < 0.001). In addition, elevated ALP and LDH levels are independent negative prognostic indicators. Moreover, we established that the area under the curve (AUC) values of the predicted 1-, 2-, and 3-year survival rates of receiver operating characteristic curve (ROC) based on the nomogram were 0.79, 0.77, and 0.74, respectively. In addition, the calibration curves and decision curve analyses (DCA) demonstrated that this model possessed strong predictive capability.Conclusion: ALP, LDH and ALP/LDH can be employed as biomarkers for predicting the prognosis of HCC. Furthermore, the nomograph based on ALH and ALP demonstrates good HCC prediction performance. For HCC patients with high ALH or ALP or ALP/LDH, close surveillance program and adjuvant therapy should be considered.Keywords: lactate dehydrogenase, alkaline phosphatase, hepatocellular carcinoma, overall survival, nomogram

Deyao Zhang,1,2,&ast; Lanqing Huo,1,3,&ast; Yangxun Pan,1,2,&ast; Zhenyun Yang,1,2,&ast; Huilan Zeng,1,2 Xin Wang,1,2 Jinbin Chen,1,2 Juncheng Wang,1,2 Yaojun Zhang,1,2 Zhongguo Zhou,1,2 Minshan Chen,1,2 Dandan Hu1,2 1Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 3Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minshan Chen; Dandan Hu, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou, 510000, People’s Republic of China, Tel +86 13902241061 ; +86 18676630499, Fax +86 8734-3115 ; +86 8734-3115, Email chenmsh@sysucc.org.cn; hudd@sysucc.org.cnPurpose: To investigate the value of preoperative systemic inflammation response (SIRS) score in predicting the prognosis of hepatocellular carcinoma (HCC) after hepatectomy.Patients and Methods: The study analyzed 1001 patients with pathologically proven HCC who received curative resection at Sun Yat-sen University Cancer Center between March 2016 and May 2020. Patients were randomly divided into a training cohort (n = 751) and a validation cohort (n = 250). Clinicopathological characteristics were collected retrospectively. The SIRS score formula was based on the results of a multivariate cox analysis of hematological inflammation indexes in the training cohort. Then, a nomogram consisting of the SIRS score was constructed and the calibration plot, areas under the receiver operating characteristic (AUC) curve, and decision curve analysis (DCA) showed good predictive ability.Results: Univariate and multivariate cox analysis revealed that the SIRS score is an independent prognostic factor for OS in HCC patients. A higher SIRS score was associated with a larger maximum lesion diameter, poor tumor differentiation, a greater possibility of vascular invasion, and a more advanced cancer stage. When the nomogram was used to predict 1-year, 3-year, and 5-year survival rates, the AUC in the training cohort was 0.763, 0.712, and 0.687, respectively; In the validation cohort, it was 0.715, 0.648, and 0.614, respectively. The AUC of this nomogram showed significantly better predictive performance than those of commonly used staging systems.Conclusion: The preoperative SIRS score has good efficacy in predicting the prognosis of HCC patients undergoing hepatectomy, and nomograms based on the SIRS score can potentially guide individualized follow-up and adjuvant therapy.Keywords: liver cancer, systemic inflammation response score, hepatocellular carcinoma, HCC, preoperative, Nomogram, prognosis

Huiqiong Zeng,1,&ast; Hanjiang Liu,2,&ast; Meifen Liu,1 Zhen Zhou,3 Shi-Bin Wang,4 Kaixia Zhou,5 Wengen Li,6 Liping Dai,1 Yashuo Chen,1 John Patrick Uy,7 Chenyu Sun,8 Zhizhong Ye1 1Department of Rheumatology, Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, People’s Republic of China; 2Department of Safety Supervision Division, Guangdong Pharmaceutical Association, Guangzhou, People’s Republic of China; 3Department of Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia; 4Department of Mental Health, Guangdong Mental Health Center, Guangdong Provincial People’s Hospital, Guangzhou, People’s Republic of China; 5Department of Clinical Laboratory, Shanghai Cancer Center, Fudan University, Shanghai, People’s Republic of China; 6Department of Rheumatology and Immunology, Meizhou People’s Hospital (Huangtang Hospital), Meizhou, People’s Republic of China; 7Department of Infectious Disease and International Health, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA; 8Department of AMITA Health Saint Joseph Hospital Chicago, University of Illinois at Chicago, Chicago, IL, USA&ast;These authors contributed equally to this workCorrespondence: Zhizhong Ye, Department of Rheumatology, Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, People’s Republic of China, Tel +852-13902477524, Email yezhizhong0506@163.com Chenyu Sun, AMITA Health Saint Joseph Hospital Chicago, University of Illinois at Chicago, 2900 N. Lake Shore Drive, Chicago, Illinois, 60657, USA, Email drsunchenyu@yeah.netBackground: The SARS-CoV-2 pandemic has imposed substantial health and economic burdens on the societies. COVID-19 vaccination is the most effective method of controlling the epidemic. This study assessed the attitude, willingness, and related factors of adult patients with rheumatic diseases (RDs) in China towards COVID-19 vaccination and identified their reasons for being vaccinated.Methods: A cross-sectional survey was administered to patients with rheumatic diseases from July 18 to August 18, 2021, using an online questionnaire. Logistic regression analysis was performed to examine the data.Results: We analyzed data drawn from 464 participants who provided valid responses. A total of 324 (69.83%) RD patients were not willing to be vaccinated, of which 76.97% believed that COVID-19 vaccination might exacerbate the diseases symptoms. Logistic regression analysis showed that a combination of experiencing systemic damage, being in the acute attack stage of the disease, and fear of the adverse impact of vaccination on rheumatism, etc., were the predominant factors affecting the intentional vaccination rate in adult patients with rheumatic diseases (p < 0.05).Conclusion: The COVID-19 intentional vaccination rate was relatively low in adult Chinese patients with RD. Public health education and the dissemination of government scientific data for patients with RD should be enhanced to increase COVID-19 vaccination rates.Keywords: China, rheumatic disease, COVID-19, vaccination, attitude, willingness

Zhenyun Yang,1,2,* Deyao Zhang,1,2,* Huilan Zeng,1,2,* Yizhen Fu,1,2 Zili Hu,1,2 Yangxun Pan,1,2 Jinbin Chen,1,2 Juncheng Wang,1,2 Yaojun Zhang,1,2 Zhongguo Zhou,1,2 Li Xu,1,2 Dandan Hu,1,2 Minshan Chen1,2 1State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dandan Hu; Minshan Chen, Tel +86-20-87343828 ; +86-20-87343117, Fax +86-20-87343585, Email hudd@sysucc.org.cn; chenmsh@sysucc.org.cnPurpose: Inflammatory response is related to tumor progression and patient survival. We aimed to clarify the prognostic value of the inflammation-based scores in intrahepatic cholangiocarcinoma (ICC) patients receiving anti-PD1 therapy.Patients and Methods: A total of 73 patients who received anti-PD-1 therapy from February 2019 to February 2021 were included in the study. Representative inflammation-based prognostic scores, including C-reactive protein (CRP), the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-CRP ratio (LCR), lymphocyte-to-monocyte ratio (LMR), systemic immune inflammation index (SII), CRP-to-albumin ratio (CAR), prognostic nutritional index (PNI), Glasgow Prognostic Score (GPS), and prognostic index (PI), were assessed for prediction accuracy using Kaplan–Meier survival curves and time-dependent receiver operating characteristic (ROC). All the ten inflammation-based prognostic scores were measured before receiving anti-PD1 therapy.Results: All the ten inflammation-based prognostic scores showed good discriminatory ability in terms of overall survival (OS) (all P < 0.01), the higher the score, the worse the prognosis, while the CRP score was a remarkable independent predictor for OS in multivariate analysis (hazard ratio, 6.032; confidence interval, 2.467– 14.752; P < 0.001). The area under the ROC curve at 6 months, 12 months, 18 months and 24 months consistently demonstrated that the predictive value of the CRP score was superior to other inflammation-based scores.Conclusion: Inflammation-based scores predict the efficacy of anti-PD-1 therapy in patients with ICC and CRP score superior to the other inflammation-based prognostic scores in terms of predictive ability.Keywords: inflammation-based score, intrahepatic cholangiocarcinoma, anti-PD-1 treatment, overall survival, C-reactive protein

Tianyu Liu,1,&ast; Zhiyong Cheng,2,&ast; Shiya Zou,3,&ast; Chao Xu,4 Shoudong Pan,3 Huabei Zeng,2 Yidong Shan,2 Yi Feng,1 Hong Zhang1 1Department of Anesthesiology, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Anesthesiology, Suqian Maternity Hospital, Suqian, Jangsu, People’s Republic of China; 3Department of Anesthesiology, Capital Institute of Pediatrics Affiliated Children’s Hospital, Beijing, People’s Republic of China; 4Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Feng; Hong Zhang, Department of Anesthesiology, Peking University People’s Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, People’s Republic of China, Tel +86-13601083503 ; +86-13311281808, Email doctor_yifeng@sina.com; zhangh_18@sina.comPurpose: Many previous trials have compared the effects of different vasoactive drugs on cesarean section patients, but their infusion rate is based on experience rather than high-quality evidence. It is difficult to judge whether the effect of vasoactive drug comes from the better choice or a more appropriate at rates of vasoactive drugs. The effect of vasoactive drugs at the rates of the 90% effective dose needs to be verified and compared.Patients and Methods: Women undergoing elective caesarean delivery under combined spinal-epidural anaesthesia were randomized to receive phenylephrine or norepinephrine or metaraminol infusion at the rate that was assumed to be the 90% effective dose. Anesthetic management was standardized and included fluid loading with 10 mL/kg of Ringer. The primary outcome was the umbilical artery pH.Results: 78 patients were included. The umbilical artery pH was not significantly different among the three groups (phenylephrine group: 7.33 ± 0.03 vs norepinephrine group: 7.33 ± 0.04 vs metaraminol group: 7.33 ± 0.04, P = 0.99). There were no significant differences in the incidence of hypotension, hypertension, bradycardia, and nausea and vomiting among the three groups. The SBP of the phenylephrine group was significantly higher than that of the metaraminol group (adjustive P value = 0.005).Conclusion: Phenylephrine (0.54 μg/kg/min) or metaraminol (2 μg/kg/min) or norepinephrine (0.08 μg/kg/min) administered to healthy patients with elective cesarean section after spinal anesthesia has no significant effect on the acid-base balance of the fetus.Keywords: cesarean section, vasoactive drugs, foetal acid-base balance, randomized controlled trial

Herui Li,&ast; Yiming Ma,&ast; Zihang Zeng, Lijuan Luo, Tiao Li, Huihui Zeng, Yan Chen Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Chen; Huihui Zeng, Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, 410011, Hunan, People’s Republic of China, Email chenyan99727@csu.edu.cn; bonemarrow@csu.edu.cnBackground: Surgical and medical treatments are applied to pulmonary cryptococcosis (PC) in the real world, while the prognosis of different therapies is uncertain. This study investigated diagnosis, real-world therapy, follow-up outcomes, and prognosis factors, aiming to deepen our understanding of PC.Methods: Patients pathologically diagnosed with PC were retrospectively reviewed and followed up. Further comparisons and subgroup analyses were conducted in surgical and nonsurgical treatment individuals. Univariable and multivariable logistic regression methods were used to explore the risk factors associated with treatment failure.Results: One hundred and sixty-three patients were included in this study, of whom 92 underwent surgical removal of VATS or open lung surgery (68 of them received postoperative antifungal treatment) and 71 got antifungal drugs only. Compared with nonsurgical patients, surgical patients were more immunocompetent (73 [79.3%] cases vs 33 [46.5%]), showed milder symptoms and more limited pulmonary lesions. Although they had instant treatment response owing to lesions resection, there is no significant advantage in the rate of treatment failure. Multivariable regression showed independent predictive factors associated with treatment failure were polymorphonuclear (PMN)> 6.30&ast;109/L, albumin (Alb) < 40g/L and antifungal dosage < 400mg/d. Further analysis among patients with different immune statuses or symptoms demonstrated that sufficient antifungal dosage could reduce the rate of treatment failure.Conclusion: PC showed variable and nonspecific clinical features. PC patients with limited nodules/masses and mild symptoms often led to misdiagnosis and unnecessary lung resections. The potential risk factors including higher PMN and hypoalbuminemia could help clinicians to identify PC patients with poor treatment efficiency at an early stage. To note, sufficient antifungal dosage may improve the treatment outcomes.Keywords: pulmonary cryptococcosis, diagnosis, antifungal treatment, clinical features, surgery

Yumei Wu,1 Hui Zeng,2 Meiping Zhang,1 Chunyan Li,2 Yuanlin Tang,2 Xiufen Li,1 Shanyou Yuan,3 Qifeng Wei,3 Jinghua Wang,4 Xianjia Ning,4 Xiaoyin Zhang1 1Department of Gastroenterology, the Third People’s Hospital of Shenzhen, Shenzhen, Guangdong Province, People’s Republic of China; 2Department of Health Management, the Third People’s Hospital of Shenzhen, Shenzhen, Guangdong Province, People’s Republic of China; 3Department of Orthopedics, the Third People’s Hospital of Shenzhen, Shenzhen, Guangdong Province, People’s Republic of China; 4Centre of Clinical Epidemiology, the Third People’s Hospital of Shenzhen, Shenzhen, Guangdong Province, People’s Republic of ChinaCorrespondence: Xiaoyin Zhang, Department of Gastroenterology, the Third People’s Hospital of Shenzhen, 29 Bulan Road, Longgang District, Shenzhen, Guangdong Province, 518112, People’s Republic of China, Tel +86-755-61222333, Fax +86-755-61238928, Email xhnk_01@163.com Xianjia Ning, Center of Clinical Epidemiology, the Third People’s Hospital of Shenzhen, 29 Bulan Road, Longgang District, Shenzhen, Guangdong Province, 518112, People’s Republic of China, Tel +86-755-61222333, Fax +86-755-61238928, Email xning@tmu.edu.cnPurpose: Helicobacter pylori is one of the most common causes of peptic ulcers, gastritis, and gastric cancers. This study investigated sex-specific differences in the prevalence of H. pylori infection and its associated factors among individuals undergoing hospital-based health examinations in southern China.Methods: This study enrolled consecutive healthy individuals who underwent regular health examinations at a hospital physical examination center between September 2020 and September 2021. Anthropometric characteristics and biochemical profiles were measured. All individuals underwent carbon-13 urea breath tests. Univariate and multivariate analyses were used to evaluate the factors associated with H. pylori infection.Results: A total of 5035 individuals (men, 59.1%; women, 40.9%) were included in the analyses. The total rate of H. pylori infection was 35.0% (men, 35.5%; women, 34.3%). In the multivariate analysis, the risk factors identified for H. pylori infections were high fasting blood glucose levels and blood pressure ≥ 160 mmHg in men and older age, high body mass index, and low albumin levels in women.Conclusion: These findings suggest that physicians must be aware of the metabolic factors associated with H. pylori infections in the Chinese population. Early detection of these factors and timely intervention are expected to reduce H. pylori infections and provide a theoretical basis for the primary prevention of several gastrointestinal diseases.Keywords: Helicobacter pylori infection, gastrointestinal disease, sex differences, prevalence, metabolic factors

Yue Liu,1,2 Bidong Fu,2 Zichuan Yu,2 Gelin Song,2 Hong Zeng,2 Yiyang Gong,2 Yongqi Ding,2 Da Huang3 1Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of China; 2Second College of Clinical Medicine, Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of China; 3Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of ChinaCorrespondence: Da Huang, Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 13576113993, Email danmo0904@163.comPurpose: Hepatocellular carcinoma (HCC) is a malignancy with high incidence, but its prognosis is not optimistic. KRBA1 is a member of the KRAB family and participates in the regulation of gene transcription. However, no studies have focused on the role of KRBA1 in HCC.Patients and Methods: In this study, we first analyzed the expression of KRBA1 in HCC using TCGA and ICGC databases and validated by Immunohistochemistry in clinical HCC samples. The Wilcoxon rank-sum test was used to determine the relationship between KRBA1 expression and clinicopathological features. Subsequently, we used Kaplan-Meier online website analysis and Cox regression model to predict the prognostic value of KRBA1 in HCC patients. Furthermore, the functions of KRBA1 were identified by enrichment analysis. TIMER and GSCALite were used to investigate the relationship between KRBA1 expression in HCC and immune infiltration and drug targets, respectively. Finally, the relationship between KRBA1 expression and m6A modification in HCC was analyzed using the TCGA and ICGA datasets.Results: The results showed that KRBA1 was upregulated in HCC and was associated with many clinicopathological features. High KRBA1 causes poor overall survival and may be an independent risk factor for HCC. KRBA1 tends to be hypermethylated and associated with poor prognosis in HCC compared with normal tissues. Enrichment analysis indicates that KRBA1 is associated with cell cycle and immune processes, and TIMER analysis shows that KRBA1 expression is associated with infiltration levels and immune characteristics of various immune cells. Silenced KRBA1 evidently reduced three chemokine expression in HCC cells. Drug sensitivity analysis showed that KRBA1 was sensitive to 39 drug small molecules. KRBA1 showed a strong positive correlation with five m6A related genes.Conclusion: KRBA1 is a prognostic biomarker associated with HCC immunity and m6a modification, serving as an effective target for the diagnosis and treatment of HCC.Keywords: KRBA1, prognosis, biomarker, immune infiltration, hepatocellular carcinoma, m6A modification

Huihui Zeng,1– 3 Yiming Ma,1– 3 Xue He,1– 3 Shan Cai,1– 3 Ping Chen,1– 3 Yan Chen,1– 3 Hong Luo1– 3 1Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2Research Unit of Respiratory Diseases, Central South University, Changsha, Hunan, People’s Republic of China; 3Hunan Centre for Evidence-Based Medicine Changsha, Hunan, People’s Republic of ChinaCorrespondence: Hong LuoDepartment of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital of Central South University, No. 139 Renmin Road, Changsha, Hunan, 410011, People’s Republic of ChinaEmail luohonghuxi@csu.edu.cnBackground: Organizing pneumonia (OP) is a secondary process in many diseases. Due to its low incidence and indistinct symptoms, there is limited information on OP associated with haematological malignancies. Therefore, the aim of this study was to discuss the characteristics and prognosis of OP associated with haematological malignancies.Methods: We observed and analysed pathologically confirmed OP cases associated with haematological malignancies in a hospital record database and excluded cases of OP with known causes, including chemotherapy, radiotherapy, targeted therapy, transplantation and infection.Results: There were five patients with OP underlying only haematological malignancies, including one case each of the following: myelodysplastic syndrome, acute myelogenous leukaemia, multiple myeloma, aplastic anaemia, and T cell lymphoma. Radiological findings did not show a distinct pattern, and two cases mimicked pulmonary aspergillosis with ground-glass opacity (GGO). The diagnosis of OP was confirmed by minimal invasive biopsy. Although all patients developed severe cases, steroids yielded favourable outcomes.Conclusion: This study demonstrates that haematological malignancies may be a cause of OP and that minimal invasive biopsy may be an effective and safe method to confirm the diagnosis. Although OP associated with haematological malignancies may more frequently develop into severe cases, the OP lesions were steroid-responsive during follow-up.Keywords: organizing pneumonia, haematological malignancies, characteristics, follow-up

Yanxiang Shao,1,&ast; Xiang Tu,1,&ast; Yang Liu,1,&ast; Yige Bao,1 Shangqing Ren,1,2 Zhen Yang,1,3 Xu Hu,1 Kan Wu,1 Hao Zeng,1 Qiang Wei,1 Xiang Li1 1Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Robotic Minimally Invasive Surgery Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, People’s Republic of China; 3Department of Urology, Chengdu Second People’s Hospital, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang LiDepartment of Urology, West China Hospital, Sichuan University, 37 GuoXueXiang, Chengdu, Sichuan, People’s Republic of ChinaTel +86 18980601428Email xiangli87@hotmail.comObjective: To investigate the predictive factors of lymph node metastasis (LNM) and evaluate the usefulness of prediction nomograms.Methods: This study included 300 patients diagnosed with penile squamous cell carcinoma at West China Hospital (WCH) of Sichuan University (Chengdu, China) and 412 cases acquired from the Surveillance, Epidemiology, and End Results (SEER) program. Logistic regression analysis was performed on these cohorts to investigate the predictive factors of LNM. We evaluated a recently developed prediction nomogram for LNM, which was established based on the National Cancer Database (NCDB). Moreover, we developed a novel nomogram using cases from the WCH for the prediction of lymphatic metastasis.Results: Logistic analysis identified that younger age at diagnosis, invasion of the penis body, poorer pT stage, cN stage, nuclear grade and the presence of lymph vascular invasion (LVI) were significantly correlated with LNM in WCH cases; however, only race, poorer T stage and cN stage were significantly associated with LNM among the cases from the SEER. Multivariate analysis demonstrated that younger age, poorer T stage, cN stage and nuclear grade were independent predictors of LNM. Receiver operating characteristic curve analysis of WCH cases showed that the tumor T stage 8th edition has better area under the curve than 7th stage (0.672 vs 0.636, respectively). Moreover, well AUC was seen in external validation of NCDB nomogram in WCH cohorts and SEER series (0.833 vs 0.795). The new nomogram included the aforementioned independent predictors and the bootstrap-corrected concordance was 0.876.Conclusion: Younger diagnose age, poorer pT stage, cN stage, nuclear grade and LVI were the most important predictors of LNM in patients with penile cancer. 8th T stage performed better than 7th version in predicting LNM. NCDB nomogram has some application values in both WCH and SEER cases, and our novel model further improved the predictive accuracy.Keywords: penile cancer, lymph node metastasis, prediction model, nomogram, SEER

Xudong Zhu,1,2,&ast; Xingming Zhang,1,2,&ast; Guangxi Sun,1,2,&ast; Zhenhua Liu,1,2,&ast; Haoran Zhang,1,2 Yaojing Yang,1,2 Yuchao Ni,1,2 Jindong Dai,1,2 Sha Zhu,1,2 Junru Chen,1,2 Jinge Zhao,1,2 Zhipeng Wang,1,2 Hao Zeng,1,2 Pengfei Shen1,2 1Department of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengfei ShenDepartment of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu, 610041, Sichuan, People’s Republic of ChinaEmail cdhx510@163.comHao ZengDepartment of Urology, West China Hospital, Sichuan University, No. 37 Guoxue Xiang, Chengdu, 610041, Sichuan, People’s Republic of ChinaEmail kucaizeng@163.comPurpose: To investigate the survival benefit and safety of individualized schedules for sunitinib in patients with metastatic renal cell carcinoma (mRCC) through plasma concentration monitoring.Methods: A total of 105 patients with mRCC were enrolled. The schedule was adjusted in two ways: therapeutic drug monitoring (TDM) and toxicity-adjusted schedule (TAS). One group of patients were without any schedule adjustment (maintained schedule, MAS). Progression-free survival (PFS), overall survival (OS), tumor response, and adverse events (AEs) were compared. The relationship between AEs and steady-state concentration or consecutive monitoring curves was explored. Further monitoring of individualized schedules was also conducted.Results: Based on the plasma concentration, the schedules of 18 patients were adjusted in the TDM group. The schedules were adjusted in 37 patients due to severe AEs in the TAS group, while 50 patients were without any schedule adjustment. The median PFS and OS were better in the TDM group than the other two groups (p = 0.001 and p = 0.004, respectively). Univariate and multivariate analyses indicated that TDM could decrease the risk of death independently (p = 0.026). Moreover, the incidence of grades 3/4 AEs decreased from 88.9% to 33.3% in the TDM group (p = 0.001). Sunitinib concentration in 150– 200ng/mL was regarded as a “transitional zone” due to severe AEs mainly happened when concentration elevated over it. After TDM, further plasma concentration monitoring indicated that individualized schedules enabled sunitinib concentration to fluctuate in a much safer range.Conclusion: Treatment-related toxicities could be minimized through plasma concentration monitoring. Patients with adjusted schedules by therapeutic drug monitoring could achieve better survival benefits.Keywords: sunitinib, plasma concentration, metastatic renal cell carcinoma, individualized schedule adjustment, clinical outcomes

LianLi Duan,1,&ast; Jinyong Zhang,1,&ast; Zhifu Chen,1 Qiang Gou,1 Qingshan Xiong,1 Yue Yuan,1 Haiming Jing,1 Jiang Zhu,2 Li Ni,3 Yuling Zheng,4 Zhiyong Liu,5 Xiaokai Zhang,1 Hao Zeng,1 Quanming Zou,1 Zhuo Zhao1 1National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing, 400038, People’s Republic of China; 2Department of Pathology, Southwest Hospital, Army Medical University, Chongqing, 400038, People’s Republic of China; 3Obstetrics and Gynecology, The First People’s Hospital of Jiulongpo District, Chongqing, 400050, People’s Republic of China; 4State Key Laboratory of Pathogens and Biosecurity, Institute of Microbiology and Epidemiology, Beijing, 100071, People’s Republic of China; 5Department of Laboratory Medicine, Southwest Hospital, Army Medical University, Chongqing, 400038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuo Zhao; Quanming Zou Email zhaozhuo198309@163.com; qmzou2007@163.comPurpose: We previously reported that monoclonal antibody (mAb) cocktail improves survival in Staphylococcus aureus infection. In this study, we used acute pneumonia model and lethal sepsis model to investigate the efficacy of antibiotic combined with epitope-specific mAb cocktail in treating MRSA252 infection.Methods: MRSA252 was challenged by tail vein injection or tracheal intubation to establish sepsis model or pneumonia model. One hour after infection, the mice received a single intravenous injection of normal saline, vancomycin, and vancomycin combined monoclonal antibody, linezolid alone or linezolid combined monoclonal antibody. Daily record survival rate (total 7 days), bacterial load, histology, cytokine analysis of serum and alveolar lavage fluid, and in vitro determination of the neutralizing ability of antibodies to SEB toxin and Hla toxin explained the mechanism of antibody action.Results: The mAb cocktail combined with low doses of vancomycin or linezolid improved survival rates in acute pneumonia model (70%, 80%) and lethal sepsis model (80%, 80%). Epitope-specific monoclonal antibodies reduced bacterial colonization in the kidneys and lungs of mice and inhibited the biological functions of the toxins Hla and SEB in vitro. Compared to the antibiotic alone or PBS groups, the combination group had higher levels of IL-1α, IL-1β and IFN-γ and lower levels of IL-6, IL-10, TNF-α. Further, the combination of antibiotic and mAb cocktail improved infection survival against the clinical MRSA isolates in a lethal sepsis model.Conclusion: This study demonstrates a novel method to treat people with low immunity against drug-resistant S. aureus infections.Keywords: methicillin-resistant Staphylococcus aureus, immunodominant epitope, monoclonal antibody, lethal sepsis, pneumonia

Yanxiang Shao,1,&ast; Thongher Lia,1,&ast; Yaohui Wang,1,&ast; Kan Wu,1 Xu Hu,1 Yang Liu,1 Shuyang Feng,1 Shangqing Ren,1,2 Zhen Yang,1,3 Sanchao Xiong,1 Weixiao Yang,1 Qiang Wei,1 Hao Zeng,1 Xiang Li1 1Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Robotic Minimally Invasive Surgery Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, 610072, People’s Republic of China; 3Department of Urology, Chengdu Second People’s Hospital, Chengdu, 610021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang LiDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, 37 GuoXueXiang, Chengdu, 610041, People’s Republic of ChinaEmail xiangli87@hotmail.comObjective: To evaluate the prognostic factors of penile cancer and the utility of prognostic models.Methods: We analyzed postoperatively collected data of 311 patients diagnosed with penile cancer. Survival analysis (Kaplan–Meier and cox regression methods) was performed on this cohort. The c-index was used to determine the predictive accuracies of potential prognostic factors. The accuracies of four prognostic models were also evaluated, which were AJCC prognostic stage group for three recent editions, and four nomograms constructed by the Surveillance, Epidemiology, and End Results program (SEER). Two novel nomograms using our data were created and AUC of 2-year survival were determined to compare existing and newly established models.Results: Tumor site, T and N stages, nuclear grade and lymph vascular invasion (LVI) significantly influenced prognosis. The 8th T and N stages had better c-indexes than former editions, while no improvement was seen in the 8thAJCC stage group. 6th AJCC+grade nomogram had a higher c-index than other three nomograms (SEER+grade, 6th TNM+grade, and 6th T1-3N0-3+grade nomograms; c-index: 0.831 vs 0.738, 0.792 and 0.781). New nomogram 1 included the 8th T and N stages, tumor site, nuclear grade, and LVI, with a c-index of 0.870. Novel nomogram 2 replaced the T and N stages with the AJCC stage group, which had a lower c-index of 0.855. The order of prediction accuracy of 2-year survival in the old and new models is consistent with the c-index results.Conclusion: Tumor site, stages, grade, and LVI play important roles in predicting survival of penile cancer. The 8th stages have better predictive accuracy than former editions. We proposed two models with better predictive accuracy than former models; specifically, nomogram 1 may be a more precise and convenient tool for predicting penile cancer outcomes.Keywords: penile cancer, TNM stage, survival, nomogram, external validation

Qiaoping Li,1,&ast; Ziwei Huang,2,&ast; Defu Liu,3 Jingna Zheng,1 Jianhui Xie,4– 6 Jiannan Chen,1 Huifang Zeng,2 Ziren Su,1 Yucui Li1 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 2The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China; 3School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 4The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 5State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 6Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yucui Li; Ziren SuGuangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of ChinaTel +86 20 39358517Fax +86 20 39358390Email liyucui@gzucm.edu.cn; suziren@gzucm.edu.cnPurpose: Berberine (BBR) is an active component of Phellodendri Cortex (PC), which is a traditional Chinese medicine that has been prescribed clinically for hyperuricemia (HUA) for hundreds of years. Many studies reported the anti-inflammatory and nephroprotective properties of BBR and PC; however, the therapeutic effects of BBR on HUA have not been explored. This study aims to investigate the efficacy and mechanism of BBR for treating HUA.Methods: The mechanism of BBR in the treatment of HUA were predicted by network pharmacology. A mouse model of HUA established by potassium oxonate and hypoxanthine was used to verify the prediction. The levels of serum uric acid (UA), urea nitrogen (BUN) and creatinine (CRE) were determined by biochemical test kits. Hematoxylin and eosin staining of kidney tissues was used to observe the kidney damage. ELISA kits were applied to detect the levels of interleukin (IL)-1β and IL-18 in serum and kidney tissues. Quantitative real-time PCR and Western blotting were adopted to analyze the expression of NLRP3, ASC, Caspase1, IL-1β and URAT1. The expressions of URAT1 in the kidney tubules were visualized by immunohistochemical staining. Molecular docking was used to assess the interaction between URAT1 and BBR.Results: The network pharmacology screened out 82 genes and several inflammation-related signaling pathways related to the anti-hyperuricemia effect of BBR. In the in vivo experiment, BBR substantially decreased the level of UA, BUN and CRE, and alleviated the kidney damage in mice with HUA. BBR reduced IL-1β and IL-18, and downregulated expressions of NLRP3, ASC, Caspase1 and IL-1β. BBR also inhibited expression of URAT1 and exhibited strong affinity with this target in silico docking.Conclusion: BBR exerts anti-HUA and nephroprotective effects via inhibiting activation of NLRP3 inflammasome and correcting the aberrant expression of URAT1 in kidney. BBR might be a novel therapeutic agent for treating HUA.Keywords: berberine, hyperuricemia, URAT1, NLRP3 signaling pathway

Hongfang Zeng,1– 3,&ast; Xiaoli Li,1– 3,&ast; Duanfang Zhou,1– 3 Ning Wang,4 Xiaoping Yu,1– 3 Liangyuan Long,1,3 Hao Cheng,5,6 Shuyu Zhou,5 Zhengze Shen,7 Weiying Zhou1– 3 1Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Drug Metabolism, Chongqing, People’s Republic of China; 3Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People’s Republic of China; 4West China Biopharm Research Institute, West China Hospital, Chengdu, Sichuan Province, 610041, People’s Republic of China; 5China Company 18th, College of Pharmacy, Army Medical University, Chongqing, 400038, People’s Republic of China; 6Department of Pharmacy, Medical Security Center, the 925 Hospital, Joint Logistic Support Force, Guiyang, Guizhou Province, 550005, People’s Republic of China; 7Department of Pharmacy, Yongchuan Hospital Affiliated to Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiying ZhouDepartment of Pharmacology, College of Pharmacy, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of ChinaTel/Fax +86 23 684 85161Email wyzhou0118@163.comPurpose: To examine the pharmacological effects of Qihu on type 2 diabetes mellitus using db/db mice.Materials and Methods: Thirty-seven db/db mice were randomly divided into the following 5 groups: diabetes model control group (DM group; n = 7), administered with the adjuvant 0.3% carboxymethyl cellulose-Na; positive control group (Met group; n = 8), administered with metformin (0.13 g/kg bodyweight); Qihu-L group (n = 7), administered with a low dose of Qihu (0.75 g/kg bodyweight), Qihu-M group (n = 7), administered with a medium dose of Qihu (1.5 g/kg bodyweight); Qihu-H group (n = 8), administered with a high dose of Qihu (3.0 g/kg bodyweight). BKS mice (n = 8) were used as the negative control group. The db/db mice were administered with drugs through oral gavage for 28 days. The random blood glucose levels, glucose tolerance test, bodyweight, food intake, and blood lipid levels of the mice were measured during the experimental period. The liver and pancreas tissues were collected for pathological, quantitative real-time polymerase chain reaction, and Western blotting analyses.Results: Compared with the DM group, the Qihu groups exhibited decreased bodyweight gain. The blood glucose levels in the Qihu-L, Qihu-M, and Qihu-H were 31.46%, 43.73%, and 51.83%, respectively, lower than those in the DM group. The triglyceride levels were significantly downregulated and the swelling and steatosis of the hepatocytes were significantly lower in the Qihu-M and Qihu-H groups than in the DM group. Qihu downregulated the expression of IL-1β, IL-6, and TXNIP and upregulated the AMP-activated protein kinase (AMPK) signaling pathway in the pancreas and liver tissues of db/db mice.Conclusion: The anti-diabetic effects of Qihu are mediated through the activation of the AMPK/Txnip signaling and the downregulation of the secretion of inflammatory factors in db/db mice.Keywords: type 2 diabetes mellitus, T2DM, Traditional Chinese medicine, TCM, TXNIP, anti-inflammatory

Hong Zeng, Yongqiang Wei, Xiaolei Wei, Ru Feng Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Ru FengDepartment of Hematology, Nanfang Hospital, Southern Medical University, 1838 Guanzghou Avenue, Guagzhou, Guangdong, 510515, People’s Republic of ChinaTel +86-13922865798Email rufeng2000@21cn.comIntroduction: Emerging evidence has revealed that long noncoding RNA (lncRNA) play important role in almost all kinds of human cancers. LINC00908 has been reported to be involved in the development of prostate cancer, colorectal cancer and gastric cancer which was functioned as an oncogene. However, the potential biology role and molecular mechanism of LINC00908 in diffuse large B-cell lymphoma are still unclear.Methods: LINC00908 and miR-671-5p expression were evaluated in DLBCL tissues and cell lines using RT-qPCR. CCK-8 and transwell assay were used to analyze the in vitro role of LINC00908 in DLBCL progression. The xenograft model was used to explore the in vivo role of LINC00908 in DLBCL growth. The physical interaction between LINC00908 and miR-671-5p was confirmed using bioinformatics analysis and a dual luciferase assay, RIP and RNA pull down.Results: The expression of LINC00908 was markedly up-regulated in diffuse large B-cell lymphoma tissues and cell lines, and the decreased expression of LINC00908 significantly inhibited diffuse large B-cell lymphoma cell proliferation and invasion. Then, we revealed that LINC00908 directly interacted with miR-671-5p, which was down-regulated in diffuse large B-cell lymphoma cells and highly expressed with LINC00908 knockdown. Moreover, luciferase reporter assays and RNA immunoprecipitation (RIP) assay further proved that miR-671-5p is a direct target of LINC00908 in diffuse large B-cell lymphoma cells. Rescue experiments were also performed, and we confirmed that LINC00908 acts as an oncogene role in diffuse large B-cell lymphoma through miR-671-5p. Finally, the influence of LINC00908 silence significantly inhibited diffuse large B-cell lymphoma growth in vivo.Conclusion: LINC00908 promotes malignancy of diffuse large B-cell lymphoma through regulating miR-671-5p.Keywords: LINC00908, diffuse large B-cell lymphoma, miR-671-5p, proliferation, invasion

Yuejie Xu,1,* Lei Xu,1,* Weijing Zhao,1 Qing Li,1 Ming Li,1 Wei Lu,1 Hui Zeng,1 Jinhua Yan,2 Daizhi Yang,2 Wei Wu,3 Jianping Weng,2 Jiemin Pan,1 Fang Liu1 1Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, 200233, People’s Republic of China; 2Department of Endocrinology and Metabolic Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 3Department of Pediatrics, Tongji Hospital, Wuhan Tongji Medical University, Wuhan, Hubei, 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiemin Pan; Fang LiuDepartment of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, 600 Yishan Road, Xuhui District, Shanghai, 200233, People’s Republic of ChinaTel +86-18930173803Email lilypjm@hotmail.com; f-liu@sjtu.edu.cnPurpose: Smartphones have received increasing attention and achieved positive outcomes in diabetes intervention. The widespread use of WeChat in China provides an opportunity for self-management practices in patients with diabetes. Nevertheless, how to combine the strengths of the WeChat platform with traditional medical strategy remains to be explored. This study aimed to evaluate the efficacy of a novel flash glucose monitoring device combined with the WeChat platform in juvenile type 1 diabetes management.Patients and Methods: A total of 60 juvenile patients with type 1 diabetes were randomly assigned into three groups: a blood glucose self-monitoring group (group A), a flash glucose monitoring (group B), and a flash glucose monitoring combined WeChat-interactive management group (group C). The intergroup differences in demographics, biochemical indicators, and questionnaire scores of the Diabetes Monitoring and Treatment Satisfaction Questionnaire and Diabetes Specific Quality of Life assessment were compared at the baseline and after 6 months.Results: After the 6-month intervention, groups B and C showed significantly lower glycated hemoglobin A1c (HbA1c) levels compared to those observed at baseline (both P < 0.05), with the largest decrease observed in group C (group B vs group C, P =0.04). Hypoglycemic episodes per month decreased from baseline in groups B and C (both P < 0.05) and were more significant in group C (P < 0.001). In addition, the DMTSQ scores increased in the 6th month in all groups (all P < 0.05), and the largest rise in scores was found in group C, followed by groups B and A. The DQOL scores in groups B and C decreased significantly from the baseline (both P < 0.05), with no change in group A.Conclusion: Flash glucose monitoring combined with the WeChat-interactive system may help achieve sustained glycemic control and higher satisfaction in patients with juvenile type 1 diabetes.Trial Registration: This study was registered at chictr.org.cn, number ChiCTR1900025495. Registered 29 August 2019.Keywords: WeChat, type 1 diabetes, self-management, glycated hemoglobin A1c

Jun Zhou,1,* Suying Wang,2,* Lun Zhu,3 Luting Zhou,1 Hong Zeng,4 Yongli Gan,2 Chaofu Wang1 1Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pathology, Ningbo Clinical and Pathological Diagnostic Center, Ningbo, Zhejiang, People’s Republic of China; 3Department of Pathology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chaofu WangDepartment of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 2st Ruijin Road, Huangpu District, Shanghai, People’s Republic of ChinaEmail wangchaofu@126.comAim: The concrete features of expression of terminal deoxynucleotidyl transferase (TdT) are needed to be revealed in male and female germ cell tumors (GCTs).Methods: TdT immunostaining was performed in 195 GCTs, and the tumor and/or tumorous components included seminomas, germ cell neoplasias in situ (GCNISs), dysgerminomas, embryonal carcinomas (ECs), extragonadal germinomas, yolk sac tumors (YSTs), teratomas, and spermatocytic tumors. Twenty-one sex cord-stromal tumors were also added. Expression of the classical germ cell tumor markers (PLAP, OCT4, SALL4, CD117, and D2-40) was compared to that of TDT.Results: Nearly all (tumors or tumorous components) seminomas (99%, 107/108), GCNISs (98%, 51/52), dysgerminomas (94%, 17/18), ECs (100%, 15/15), and extragonadal germinomas (100%, 11/11) were positive for TdT. None of the cells in YSTs (0/38), teratomas (0/19), spermatocytic tumors (0/1), or sex cord-stromal tumors (0/21) were immunoreactive for TdT staining. The normal testicular and ovarian gonadal tissues were also negative for TdT. However, TdT presented with significant loss of antigen immunoreactivity in the paraffin-embedded tissues older than 3 years, giving rise to weak or moderate staining in a subset of cases. The expressions of TdT showed no significances with PLAP, OCT4, SALL4, CD117, and D2-40 during the diagnosis of the most GCTs (P> 0.05), except for with PLAP, SALL4, or CD117 in YST (P= 0.000 each), and D117 (P= 0.000) or D2-40 (P= 0.006) in ECs.Conclusion: Our findings further verify that TdT can serve as a new GCT marker for seminomas, GCNISs, dysgerminomas, ECs, and extragonadal germinomas, with a highly positive rate. Awareness of TdT positivity in GCTs contributes to the prevention of erroneous diagnoses, particularly in the setting of core needle biopsies. To determine the properties where TdT staining may not be apparent in some old archived paraffin-embedded tissues, one could circumvent the potential misinterpretations of false-negative immunohistochemistry results.Keywords: germ cell tumors, immunohistochemistry, TdT, pathological diagnosis

The observation of the electroweak production of a W boson and a photon in association with two jets, using pp collision data at the Large Hadron Collider at a centre of mass energy of s=13 TeV, is reported. The data were recorded by the ATLAS experiment from 2015 to 2018 and correspond to an integrated luminosity of 140 fb-1. This process is sensitive to the quartic gauge boson couplings via the vector boson scattering mechanism and provides a stringent test of the electroweak sector of the Standard Model. Events are selected if they contain one electron or muon, missing transverse momentum, at least one photon, and two jets. Multivariate techniques are used to distinguish the electroweak Wγjj process from irreducible background processes. The observed significance of the electroweak Wγjj process is well above six standard deviations, compared to an expected significance of 6.3 standard deviations. Fiducial and differential cross sections are measured in a fiducial phase space close to the detector acceptance, which are in reasonable agreement with leading order Standard Model predictions from MadGraph5+Pythia8 and Sherpa. The results are used to constrain new physics effects in the context of an effective field theory.

Ziyi Yang,1 Yi Jiang,2– 4 Min Wang,5 Huan Zeng2– 4 1The First Clinical College, Chongqing Medical University, Chongqing, People’s Republic of China; 2School of Public Health and Management, Chongqing Medical University, Chongqing, People’s Republic of China; 3Research Center for Medicine and Social Development, Chongqing Medical University, Chongqing, People’s Republic of China; 4Innovation Center for Social Risk Governance in Health, Chongqing Medical University, Chongqing, People’s Republic of China; 5North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of ChinaCorrespondence: Huan ZengPostal Address: School of Public Health and Management, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing 400016, People’s Republic of ChinaTel/Fax + 86 23 65714388Email huanzeng@cqmu.edu.cnPurpose: China is facing various societal pressures owing to its rapidly aging population. In order to provide evidence-based suggestions to promote elderly care, this study investigated the community-based elderly care centres (CBECCs) in Chongqing of China, focusing on the site selections, physical environment, facilities, and operation.Methods: All CBECCs in a district of Chongqing were analysed via a single-stage cluster sampling survey design. Descriptive statistics were used to analyse the data.Results: A total of 69 CBECCs (60 government-run and 9 collective-run centres) were identified and analysed. Most site selections were reasonable. CBECCs that were located inside of apartment complexes with entrance guards, not located on main roads, and near a market were more popular. Only 4 (13.3%) CBECCs that were not located on the ground floor were equipped with elevators. A small number of CBECCs were near a noise pollution (10.1%) or far from a medical institution (11.6%). Nearly half (42.7%) of CBECCs only had an indoor area of < 200 m2. Nearly all CBECCs had sufficient ventilation, natural lighting, and sufficient floor-to-floor height. 51.5% and 88.4% of the CBECCs fully met the criteria of ‘four rooms and one canteen’ and ‘eight functional zones’, but no significant difference was found in terms of the number of people served per month between the CBECCs that met the criteria and those that did not. A quarter of the CBECCs were operated by part-time staff. Only half provided home services (54.5%). The median of average number of people they served every month was 100 (interquartile range = 10– 300).Conclusion: Certain problems existed in the current CBECCs. Better elderly care especially calls for adequate elevator establishment, sufficient indoor and outdoor space, appropriate facilities and service, qualified managers and caregivers. A feasible and evidence-based plan to optimize the physical environment and facilities, functional layout and service provision is crucial to improve the CBECC service.Keywords: community-based elderly care centre, site selection, physical environment, facilities, cross-sectional survey, China

Qiuyang Deng,1,* Jinyong Zhang,2,* Min Zhang,1 Zhou Liu,3 Yuxin Zhong,1 Shiyi Liu,1 Ruiqin Cui,1 Yun Shi,2 Hao Zeng,2 Xiyao Yang,3 Chuchu Lin,4 Yutian Luo,5 Huaisheng Chen,5 Weiyuan Wu,6 Jinsong Wu,6 Tianle Zhang,7 Yuemei Lu,6 Xueyan Liu,5 Quanming Zou,2 Wei Huang1 1Bacteriology & Antibacterial Resistance Surveillance Laboratory, Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, People’s Republic of China; 2National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing, People’s Republic of China; 3Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Department of Nosocomial Infection Control, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, People’s Republic of China; 5Intensive Care Unit, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, People’s Republic of China; 6Department of Clinical Microbiology, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, People’s Republic of China; 7Guangdong Medical University, Dongguan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei HuangBacteriology & Antibacterial Resistance Surveillance Laboratory, Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, People’s Republic of ChinaTel +86 7522942513Fax +86 7522942514Email whuang_sz@163.comQuanming Zou National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical PharmacyCollege of Pharmacy, Army Medical University, Chongqing 400038, People’s Republic of ChinaTel/Fax +86 2368752316Email qmzou2007@163.comObjective: We aimed to establish a tool for rapid identification of KL49 Acinetobacter baumannii.Methods: Based on the capsular polysaccharide (CPS) synthesis genes database, we investigated the distribution of K locus type 49 (KL49) genes in other KL types and established a rapid identification method for KL49. We collected 61 clinical carbapenem-resistant A. baumannii (CRAB) strains, identified KL49 by gtr100 detection, and used whole genome sequencing (WGS) for verification. A mouse pneumonia model was used to confirm the hypervirulence phenotype. We tested the presence of gtr100 gene in 165 CRAB strains from three provinces in China and evaluated the correlation of gtr100 carrying CRAB infection with mortality.Results: The gtr100 gene is the CPS synthesis gene found only in KL49. We screened out nine WGS-validated KL49 strains from 61 CRAB clinical strains using polymerase chain reaction (PCR) to detect the gtr100 gene. The survival rates of KL49 strains were significantly lower than nonKL49 strains in a mouse pneumonia model. The survival rates of LAC-4 gtr100 knockout strain decreased significantly. Analysis of phylogenetics showed the worldwide spread of KL49 A. baumannii. Infection of gtr100 carrying CRAB is an independent risk for mortality (OR, 10.76; 95%CI: 3.08– 37.55; p< 0.001).Conclusion: The hypervirulence phenotype of KL49 CRAB and the association with mortality highlight the urgent need for implementing control measures. The rapid identification assay has the potential to facilitate early medical intervention and worldwide surveillance.Keywords: Acinetobacter baumannii, hypervirulent, K locus, Kaptive, mortality

Fen Zhang,1,2,* Yangjun Cai,1,3,* Biyu Diao,1 Dandan Song,1 Rongrong Miao,1 Baodan Zhang,1 Yingying Hu,1 Hanqian Zeng,1 Xiaoqu Hu1 1Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Oncology, Dajiangdong Hospital of Hangzhou First People’s Hospital Group, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Thyroid and Breast Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoqu HuDepartment of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, People’s Republic of ChinaEmail drhxj@126.comIntroduction: Gene expression association studies of tumor samples have uncovered several long non-coding RNAs (lncRNAs) closely related to various types of cancer. Several lncRNAs have been reported to play essential roles in the progression of papillary thyroid carcinoma (PTC). Novel lncRNA inhibiting proliferation and metastasis (lnc-NLIPMT) is a known regulator of mammary cell proliferation and motility, but its involvement in PTC is unclear.Materials and Methods: We investigated the role of lnc-NLIPMT in PTC by quantitative real-time polymerase chain reaction (qRT-PCR) on various PTC tissue samples and cell lines. We assessed the effects of overexpression or knockdown of lnc-NLIPMT on the proliferation, migration, and invasion of PTC cells using CCK-8, cell clone formation, and transwell assays. Changes in the expression of N-cadherin and vimentin were detected by immunoblotting.Results: Our results revealed a downregulation of the expression of lnc-NLIPMT in PTC and a negative correlation between lnc-NLIPMT expression and tumor size (P=0.006). Overexpression of lnc-NLIPMT in TPC-1 and B-CPAP cells significantly suppressed cell proliferation, migration, and invasion, while lnc-NLIPMT knockdown had the opposite effect. In addition, lnc-NLIPMT played an important role in the regulation of the expression of N-cadherin and vimentin.Conclusion: lnc-NLIPMT inhibits cell proliferation and metastasis of PTC cells and is a potential diagnostic and prognostic biomarker in PTC.Keywords: papillary thyroid carcinoma, long non-coding RNA, invasion, proliferation, metastasis

Qing Liu,1– 3 Hongbo He,1 Zhixi Duan,1,4 Hao Zeng,1 Yuhao Yuan,1 Zhiwei Wang,1 Wei Luo1 1Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Spine Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL, USA; 4Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Wei LuoDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of ChinaTel +86 15116329088Email luowei0928@126.comAim: To evaluate the clinical effect of intercalary allograft transplantation and reconstruction in the treatment of diaphyseal defect after resection of lower extremity malignant bone tumor.Methods: Clinical data of 17 patients diagnosed with malignant lower-limb bone tumors and having undergone segmental allograft reconstruction with a mean follow-up of 49.8 (26– 78) months were included. Segmental allografts of average 17-cm length preserved by deep-freezing were used and fixed using intramedullary nail, double plate, and intramedullary nail and plate combination in 2, 5, and 10 patients, respectively. Host–donor junctions were perfectly and roughly matched in 5 and 12 patients, respectively. Allograft union, local recurrence, and complications were assessed using clinical and radiological tests. Allograft union was evaluated using the International Society of Limb Salvage (ISOLS) scoring system. The functional prognosis was evaluated using the Musculoskeletal Tumour Society (MSTS) scoring system.Results: Intercalary allograft reconstruction of femoral shaft, tibial shaft, and distal tibia with ankle arthrodesis was performed in eight, four, and five patients, respectively. Two patients had local recurrence and underwent amputation; one died of metastasis. Host–donor junctions in two patients showed nonunion; 12 patients achieved bone union. The average union time was 12.1 months. No allograft fracture or infection occurred. Union rates were 100% and 88.2% at metaphyseal and diaphyseal junctions, respectively. Healing time differed significantly between the precisely and roughly matched groups (p< 0.01). The incidence of nonunion was higher after intramedullary nailing than after the other two methods (p< 0.05). The mean MSTS score was 24.2 (14– 29) at the end of follow-up.Conclusion: Intercalary allograft transplantation is an effective strategy for diaphyseal defect following post-tumor resection in the lower extremity. Good bone healing after allograft reconstruction is achieved with stable internal fixation and perfectly matched host–donor interfaces.Keywords: intercalary allograft, malignant bone tumor, bone healing, lower extremity, internal fixation

Jiqiao Yang,1,2 Li Xu,1 Pengcheng Liu,1 Zhenggui Du,1 Jie Chen,1 Faqing Liang,1 Quanyi Long,1 Di Zhang,1,3 Helin Zeng,1 Qing Lv1 1Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Clinical Research Center for Breast, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Cancer Research Institute, Kanazawa University, Kanazawa, JapanCorrespondence: Qing LvDepartment of Breast Surgery, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu 610041, People’s Republic of ChinaTel +86-2885422873Email lvqingwestchina@163.comBackground: Radioisotopes and blue dyes are used as dual tracers in the current gold standard procedure of sentinel lymph node (SLN) biopsy (SLNB) performed for breast cancer. However, the blue dye or the radioisotope as a single tracer is also being applied in some institutes. We aimed to explore the risk factors for the miss-detection of SLNs with the radioisotope and the blue dye and to describe the distribution of SLNs missed by each tracer.Patients and Methods: Patients undergoing SLNB with radioisotope and blue dye as dual mapping agents were enrolled between August 2010 and August 2018. Radioactivity count, blue dye staining status, and size and location of each SLN were prospectively documented.Results: In total, 2382 SLNs from 1010 patients were included for statistical analyses. The sentinel node identification rate was 100% for dual tracers, 99.4% for radioisotope, and 89.1% for blue dye. SLN identification using the blue dye was more likely to fail in patients undergoing breast-conserving surgery (p < 0.001) and mastectomy with reconstruction (p = 0.005). Furthermore, miss-detection was significantly more frequent in smaller and uninvolved nodes. Among all SLNs, 8.2% were located in level II and one was in level III. Notably, single tracer of blue dye tended to fail in the detection of lymph nodes in higher levels (p < 0.001).Conclusion: This study explored the association between features and the incidence of the failure to detect SLNs using radioisotope and blue dye. The locations of the miss-detected SLNs are demonstrated to provide a reference for SLNBs conducted using blue dye or radioisotope as a single tracer.Keywords: breast cancer, sentinel lymph node, radioisotope, blue dye, single tracer

Jindong Dai,1 Xingming Zhang,1 Zhenhua Liu,1 Tingni Song,2 Xudong Zhu,1 Haoran Zhang,1 Mingpeng Wu,2 Xiang Li,1 Hao Zeng,1 Pengfei Shen1 1Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 2Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of ChinaCorrespondence: Pengfei ShenDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of ChinaTel +86-28-8542-2451Email cdhx510@163.comPurpose: To assess the association between body fat components and survival status and tumor response for metastatic renal cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors (TKIs).Patients and Methods: Patients with pathologically diagnosed and radiologically indicated mRCC were enrolled into the retrospective study. Three body fat components: total fat accumulation (TFA), visceral fat accumulation (VFA) and subcutaneous fat accumulation (SFA) were measured using standard CT scans. The clinical outcomes included progression-free survival (PFS), overall survival (OS), and tumor response rates. Univariate analysis and multivariate Cox proportion hazard regression models were used to find associated parameters and to calculate the adjusted hazard ratio (HR).Results: A total of 146 patients were enrolled and the average age of patients was 56.5 years old. According to the univariate analysis, patients with an increased SFA and TFA had a longer PFS and OS. A similar phenomenon was observed among patients with ≥ 2 increasing body fat components about PFS and OS. As for multivariate analysis, SFA change (p=0.014) or the number of increasing body fat components (p=0.040) were independent indicators to predict PFS. In addition, SFA change (p=0.022) or the number of increasing body fat components (p=0.008) could independently predict OS. Moreover, a better disease control rate (p=0.028) was founded in patients with ≥ 2 increasing components. In the subgroup of patients with ≥ 2 metastasis sites, improved OS (p=0.017) and PFS (p=0.027) were found compared to those with < 2 increasing components. Further multivariate analysis identified the number of increasing body fat components was an independent factor in predicting PFS (p=0.018) and OS (p=0.029).Conclusion: Body fat accumulation, such as high SFA or TFA at progression, could improve the survival of patients with mRCC treated with TKIs, especially patients with higher tumor burden. It should be considered as an important parameter to predict the survival status of patients with mRCC.Keywords: tyrosine kinase inhibitor, body fat component, prognosis