Search

Yujian Liang,1,&ast; Chenfeng Zhao,2,&ast; Yuhang Lu,3,&ast; Kang Liao,2 Yannan Kong,4 Mengzhi Hong,2 Liubing Li,2 Yili Chen2 1Department of Pediatric Intensive Care Unit, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China; 3Zhongshan Medical School, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China; 4Department of Laboratory Medicine, the Nanhai’s Fifth People’s Hospital of Foshan, Foshan, Guangdong, 528231, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yili Chen; Liubing Li, Department of Laboratory Medicine, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China, Email chenyli3@mail.sysu.edu.cn; lilb8@mail.sysu.edu.cnBackground: Carbapenem-resistant Enterobacteriaceae (CRE) is rapidly becoming a major threat to hospitalized children worldwide. The purpose of this study was to summarize etiological characteristics and identify risk factors relevant to CRE bloodstream infection (BSI) and short-term mortality among pediatric patients in China.Methods: In this study, we included 370 inpatients ≤ 17 years old with BSI caused by Enterobacteriaceae in China from January 2013 to December 2022. By collecting data on demographics, etiological features, and clinical outcomes, we conducted an in-depth analysis.Results: Among the 370 BSI patients with infections caused by Enterobacteriaceae, 35 patients (9.46%) were caused by CRE. Among these CRE strains, Klebsiella pneumoniae (49.46%) was the most important pathogen of BSI in pediatric patients, followed by Escherichia coli (31.62%) and Enterobacter cloacae (5.95%). The most frequent carbapenemase was NDM (23/35, 65.71%), followed by KPC (8/35, 22.86%). The overall 28-day mortality rate of children with an Enterobacteriaceae BSI episode was 1.89% (7/370), of which CRE BSI patients (3/35, 8.57%) were significantly higher than CSE patients (4/335, 1.19%, P < 0.001). Congenital malformation (OR: 8.162, 95% CI: 3.859– 16.680, P < 0.001) and catheter-related (OR: 6.645, 95% CI: 3.159– 13.28, P: < 0.001) were associated with the development of CRE BSI in pediatric patients. A multivariate analysis showed that the infection of CRE (OR 7.758, 95% CI 1.869– 29.62, P = 0.021) were independent risk factors for 28-day mortality of Enterobacteriaceae BSI. When the MIC of any carbapenems was ≥ 8 μg/mL, the mortality rate in the ICU was higher (P < 0.05).Conclusion: Congenital malformation, previous cephalosporin/carbapenems administration, and catheter-related conditions were closely related to the development of CRE BSI. The mortality rate of CRE BSI was higher. NDM was the predominant carbapenemase-producing mechanism in children.Keywords: carbapenem-resistant Enterobacteriaceae, bloodstream infection

Mengdie Chen,1 Ping Feng,1 Yao Liang,2 Xun Ye,3 Yiyun Wang,2 Qiao Liu,1 Chaoyin Lu,1 Qidong Zheng,2 Lijing Wu2 1Department of Endocrinology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, People’s Republic of China; 2Department of Internal Medicine, Yuhuan Second People’s Hospital, Yuhuan, Zhejiang, People’s Republic of China; 3Department of Endocrinology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Lijing Wu, Department of Internal Medicine, Yuhuan Second People’s Hospital, No.77, Environmental Protection Middle Road, Chu Men Town, Yuhuan, Zhejiang, 317600, People’s Republic of China, Tel: +86-13777603508, Email 13777603508@163.comPurpose: This study was developed with the goal of clarifying whether there is any relationship between type 2 diabetes mellitus (T2DM) age of onset and clinical outcomes for patients in National Metabolic Management Centers (MMC).Patients and Methods: From September 2017 - June 2022, 864 total T2DM patients were recruited in MMC and assigned to those with early-onset and late-onset diabetes (EOD and LOD) based on whether their age at disease onset was ≤ 40 or > 40 years. All patients received standardized management. Baseline and 1-year follow-up data from these two groups of patients were assessed. Associations between onset age and other factors were evaluated with a multivariate linear regression approach, adjusting for appropriate covariates. Outcomes in particular subgroups were also assessed in stratified analyses.Results: Markers of dysregulated glucose metabolism and BMI values were significantly higher among EOD patients as compared to LOD patients. Subjects in both groups exhibited significant improvements in several disease-related parameters on 1-year follow-up after undergoing metabolic management. EOD patients exhibited significantly greater percentage reductions in HbA1c levels (− 28.49 (− 44.26, − 6.45)% vs − 13.70 (− 30.15,-1.60)%, P =0.017) relative to LOD patients following adjustment for confounders. Significant differences were also detected between these groups when focused on subgroups of patients who were male, exhibited a BMI ≥ 25, an HbA1c ≥ 9, or had a follow-up frequency < 2.Conclusion: Data from a 1-year follow-up time point suggest that a standardized metabolic disease management model can promote effective metabolic control in newly diagnosed T2DM patients, particularly among individuals with EOD.Keywords: age of onset, disease management, type 2 diabetes

Yali Liang,1,&ast; Yunxin Zhang,1,&ast; Yong Feng,2 Yuying Huang,2 Cuiling Zhang1 1Nursing Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2College of Nursing, Shanxi University of Chinese Medicine, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cuiling Zhang, Nursing Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, NO. 99, Longcheng Street, Xiaodian District, Taiyuan, 030032, People’s Republic of China, Tel +86-13753482546, Email sxbqezcl@163.comPurpose: To assess abusive supervision and organizational silence among nurses and investigate the mediating influence of psychological capital and fear.Background: Since the end of 2019, China’s National Development and Reform Commission (NDRC) department has decided to start the construction of regional medical centers in Shanxi, reducing cross-provincial and cross-regional medical care. In order to improve the overall standard of care in a hospital in a short period of time, health care leadership decision makers may adopt various effective leadership management practices to achieve the set goals and have high work pressure at the same time. In this case, abusive management may occur.Methods: A cross-sectional survey design was employed. In January -March 2024, a convenience sampling method was used to collect data from 470 nurses in a total of 5 hospitals in Shanxi province they were required to complete the questionnaires online anonymously. The chain mediation model was tested using the PROCESS macro program in the SPSS software and multiple linear regression model was used to verify the mediating effect.Results: Psychological capital and fear mediate the relationship between abusive supervision and nurses’ organizational silence, playing indirect mediating roles. Abusive supervision was positively associated with nurses’ organizational silence. Additionally, psychological capital plays a negative mediating role, accounting for 48.48% of the indirect effect, and fear plays a positive mediating role, accounting for 45.83% of the indirect effect. They form a chain intermediary, accounting for 5.69% of the indirect effect.Conclusion: Psychological capital and fear mediate the impact of abusive supervision on nurses’ organizational silence. Positive leadership training should be conducted to help reducing the level of head nurses’ abusive supervision behaviors, while also fostering actions that elevate nurses’ psychological capital levels.Keywords: Abusive supervision, Nurses’ organizational silence, psychological capital, fear, mediating effect

Doyoung Kwak,1 Yuanjie Liang,2 Xu Shi,3 Xi Tan2 1Department of Electrical & Computer Engineering, Texas A&M University, College Station, TX, USA; 2Novo Nordisk Inc, Plainsboro, NJ, USA; 3Department of Biostatistics, University of Michigan, Ann Arbor, MI, USACorrespondence: Xi Tan, Email mxtz@novonordisk.comPurpose: Observational research provides valuable insights into treatments used in patient populations in real-world settings. However, confounding is likely to occur if there are differences in patient characteristics associated with both the exposure and outcome between the groups being evaluated. One approach to reduce confounding and facilitate unbiased comparisons is inverse probability of treatment weighting (IPTW) using propensity scores. Machine learning (ML) and entropy balancing can potentially be used in generating propensity scores for IPTW, but there is limited literature on this application. We aimed to assess the feasibility of applying these methods for reducing confounding in observational studies. These methods were assessed in a study comparing cardiovascular outcomes in adults with type 2 diabetes and established atherosclerotic cardiovascular disease taking once-weekly glucagon-like peptide-1 receptor agonists or dipeptidyl peptidase-4 inhibitors.Methods: We applied advanced methods to generate the propensity scores compared to the original logistic regression method in terms of covariate balance. After calculating weights, a weighted Cox proportional hazards model was used to calculate the sample average treatment effect. Support Vector Classification, Support Vector Regression, XGBoost, and LightGBM were the ML models used. Entropy balancing was also performed on features identified in the original cardiovascular outcomes study.Results: Accuracy (range: 0.71 to 0.73), area under the curve (0.77 to 0.79), precision (0.53 to 0.60), recall (0.66 to 0.68), and F1 score (0.60 to 0.64) were similar between all of the advanced propensity score methods and traditional logistic regression. Among ML models, only XGBoost achieved balance in all measured baseline characteristics between the two treatment groups, closely approximating the performance of the original logistic regression. Entropy balancing weights provided the best performance among all models in balancing baseline characteristics, achieving near perfect balancing.Conclusion: Among the advanced methods examined, entropy balancing weights performed the best for optimizing balancing and can produce similar results compared to traditional logistic regression.Keywords: propensity score, machine learning, entropy balancing, type 2 diabetes, glucagon-like peptide-1 receptor agonists

Zhihan Jiang,1,&ast; Yingying Dai,2,&ast; Jing Chang,2 Pingchao Xiang,3 Zhenyu Liang,4 Yan Yin,5 Yongchun Shen,6 Ruiying Wang,7 Bianba Qiongda,8 Hongling Chu,9 Nan Li,9 Xiaoyan Gai,1,10 Ying Liang,1,10 Yongchang Sun1,10 1Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 2School of Basic Medical Sciences, Peking University, Beijing, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Peking University Shougang Hospital, Beijing, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, GuangZhou, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Shanxi Bethune Hospital, Taiyuan, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Tibet Autonomous Region People’s Hospital, Lhasa, People’s Republic of China; 9Clinical Epidemiology Research Center, Peking University Third Hospital, Beijing, People’s Republic of China; 10Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Liang; Yongchang Sun, Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, North Garden Road 49, Haidian District, Beijing, People’s Republic of China, Tel +86 13810964766 ; +86 13910979132, Fax +86 108 226 6989, Email bysyliangying@126.com; suny@bjmu.edu.cnBackground: Tuberculosis and chronic obstructive pulmonary disease (COPD) are significant public health challenges, with pulmonary tuberculosis recognized as a pivotal risk factor for the development of COPD. Tuberculosis-associated COPD is increasingly recognized as a distinct phenotype of COPD that potentially exhibits unique clinical features. A thorough understanding of the precise definition, clinical manifestations, prognosis, and most effective pharmacological strategies for tuberculosis-associated COPD warrants further investigation.Methods: This prospective, observational cohort study aims to enroll over 135 patients with tuberculosis-associated COPD and 405 patients with non-tuberculosis-associated COPD, across seven tertiary hospitals in mainland China. The diagnosis of tuberculosis-associated COPD will be established based on the following criteria: (1) history of pulmonary tuberculosis with standard antituberculosis treatment; (2) suspected pulmonary tuberculosis with radiological evidence indicative of tuberculosis sequelae; (3) no definitive history of pulmonary tuberculosis but with positive interferon-gamma release assay results and radiological signs suggestive of tuberculosis. At baseline, demographic information, medical history, respiratory questionnaires, complete blood count, interferon-gamma release assays, medications, spirometry, and chest computed tomography (CT) scans will be recorded. Participants will be followed for one year, with evaluations at six-month intervals to track the longitudinal changes in symptoms, treatment, lung function, and frequencies of COPD exacerbations and hospitalizations. At the final outpatient visit, additional assessments will include chest CT scans and total medical costs incurred.Discussion: The findings of this study are expected to delineate the specific characteristics of tuberculosis-associated COPD and may propose potential treatment options for this particular phenotype, potentially leading to improved clinical management and patient outcomes.Keywords: chronic obstructive pulmonary disease, COPD, pulmonary tuberculosis, tuberculosis-associated COPD, protocol

Xiuri Wang,1 Yunxiao Liang,1 Liuyang Hu2 1Department of Gastroenterology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530016, People’s Republic of China; 2Department of Laboratory Medicine, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530016, People’s Republic of ChinaCorrespondence: Liuyang Hu, Department of Laboratory Medicine, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530016, People’s Republic of China, Email 1225432679@qq.comAbstract: Species of Pantoea are mainly environmental strains and plant pathogens, rarely causing human infections. Here, we describe two cases of hemodialysis catheter-related bloodstream infection caused by Pantoea in patients with uremia. To our knowledge, this is the first reported case of catheter related bloodstream infection caused by Pantoea dispersa (P. dispersa) in hemodialysis patients, as well as the first case of bloodstream infection caused by Pantoea anthophila (P. anthophila). Multiple blood cultures from the catheter showed the presence of Pantoea, and the isolated P. dispersa and P. anthophila were found to be highly sensitive to various antibiotics. Prompt use of antibiotics and catheter lock with gentamicin or amikacin led to rapid recovery of the patients, avoiding the economic burden of catheter replacement. Infections caused by Pantoea might be underestimated as methods such as VITEK® MS system often result in misidentification. Therefore, we recommend using advanced techniques such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) or 16S ribosomal RNA analysis to detect more cases of Pantoea infections. By sharing these cases, we hope to increase awareness among clinicians about the potential pathogenicity of Pantoea in hemodialysis patients. It is crucial to strengthen noting the primary concern for sources of infection with Pantoea species (plant and environmental exposures) to prevent outbreaks of Pantoea-related bloodstream infections in hospitals.Keywords: hemodialysis catheter-related bloodstream infections, nosocomial bloodstream, pantoea genus, pantoea dispersa, pantoea anthophila

Chong Zhao,&ast; Shuaiqi Zhu,&ast; Yan Liang, Shuai Xu Department of Spinal Surgery, Peking University People’s Hospital, Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Liang; Shuai Xu, Department of Spinal Surgery, Peking University People’s Hospital, Peking University, Beijing, People’s Republic of China, Tel +86-010-88324110 ; +86-18811792718, Email liangyan7503@163.com; xushuairmyy@pku.edu.cnPurpose: To characterize the asymmetrical loss of bone mass and identify the association between scoliosis and osteopenia in patients with adolescent idiopathic scoliosis (AIS).Methods: Demographic information, Cobb angle, and Hounsfield unit (HU) of the neutral vertebra (NV) and apical vertebra (apex) of the major curve were collected retrospectively in 54 AIS patients. For 84 control subjects, HU values were measured at T12 and L5. Propensity score matching was performed to balance the interference of age and BMI.Results: In the AIS group, the concave and convex lateral HU of the NV and the convex lateral HU of the apex were negatively correlated with the Cobb angle. The AIS patients had lower bilateral HU. The mean HU and the apex-convex HU were also lower in the AIS group, while the apex-concave HU was slightly higher. After matching, the apex-convex HU of the AIS group remained lower, while the apex-concave HU was higher.Conclusion: Patients with AIS exhibit osteopenia, particularly on the convex side. The severity of scoliosis was found to be directly proportional to the severity of bone loss and the degree of bilateral osteopenia asymmetry. Appropriate intervention for bone loss may be able to curb the progression of scoliosis.Keywords: adolescent idiopathic scoliosis, osteopenia, osteoporosis, Hounsfield unit, propensity score matching

Parisa Shamsesfandabadi,1 Arpeet Patel,2 Yun Liang,1 Matthew J Shepard,3 Rodney E Wegner1 1Radiation Oncology department, Allegheny Health Network, Pittsburgh, PA, USA; 2Drexel University College of Medicine, Philadelphia, PA, USA; 3Neurosurgery Department, Allegheny Health Network, Pittsburgh, PA, USACorrespondence: Parisa Shamsesfandabadi, Email parisa.shamsesfandabadi@ahn.orgAbstract: Radiation therapy, a common treatment for central nervous system cancers, can negatively impact cognitive function, resulting in radiation-induced cognitive decline (RICD). RICD involves a decline in cognitive abilities such as memory and attention, likely due to damage to brain white matter, inflammation, and oxidative stress. The multifactorial nature of RICD poses challenges including different mechanisms of injury (neurogenesis, oxidative stress and neuroinflammation, dendritic structure alterations and vascular effects) and confounding factors like advanced age, and pre-existing conditions. Despite these challenges, several potential solutions exist. Neuroprotective agents like antioxidants can mitigate radiation damage, while cognitive rehabilitation techniques such as cognitive training and memory strategies improve cognitive function. Advanced imaging techniques like magnetic resonance imaging (MRI) help identify vulnerable brain areas, and proton therapy offers precise targeting of cancer cells, sparing healthy tissue. Multidisciplinary care teams are crucial for managing RICD’s cognitive and psychological effects. Personalized medicine, using genetic and molecular data, can identify high-risk patients and tailor treatments accordingly. Emerging therapies, including stem cell therapy and regenerative medicine, offer hope for repairing or replacing damaged brain tissue. Addressing RICD is vital for cancer survivors, necessitating consideration of cognitive function and provision of appropriate support and resources for those experiencing cognitive decline.Keywords: radiation therapy, radiation-induced cognitive decline, RICD, cognitive decline, cognitive function, central nervous system cancers

Yingze Hou,1,2 Can Zhu,3 Ge Ban,1 Zhean Shen,4 Yingbing Liang,5 Kun Chen,1 Chenbo Wang,1 Heng Shi4 1School of Intelligent Medical Engineering, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China; 2Clinical Medical College, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China; 3Department of Urology, The Second Clinical Medical College of Anhui Medical University, Hefei, 230032, People’s Republic of China; 4Heart Center, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, 310000, People’s Republic of China; 5Department of Chemistry and Biotechnology, Graduate School of Engineering Tottori University Koyama-Minami 4-101, Tottori, 680-8552, JapanCorrespondence: Ge Ban, School of Intelligent Medical Engineering, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China, Email bange119@qq.comAbstract: Nanoscale metal-organic frameworks (MOFs) offer high biocompatibility, nanomaterial permeability, substantial specific surface area, and well-defined pores. These properties make MOFs valuable in biomedical applications, including biological targeting and drug delivery. They also play a critical role in tumor diagnosis and treatment, including tumor cell targeting, identification, imaging, and therapeutic methods such as drug delivery, photothermal effects, photodynamic therapy, and immunogenic cell death. The diversity of MOFs with different metal centers, organics, and surface modifications underscores their multifaceted contributions to tumor research and treatment. This review is a summary of these roles and mechanisms. The final section of this review summarizes the current state of the field and discusses prospects that may bring MOFs closer to pharmaceutical applications.Keywords: metal-organic frame, oncotherapy, photothermal effect, tumor immunity, drug delivery

Sifan Ji,1,2,&ast; Hang Qi,1,2,&ast; Li Yan,1,2,&ast; Duo Zhang,1,2 Yang Wang,1,2 HaLiSai MuDanLiFu,1,2 Chuqing He,1,2 Wei Xia,1,2 Qian Zhu,1,2 Yan Liang,1,2 Jian Zhang1,2 1Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Zhang, Department of Obstetrics and Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China, Tel +86 18017316017, Email zhangjian_ipmch@sjtu.edu.cnIntroduction: Endometriosis (EM) is an estrogen-dependent benign gynecologic disease affecting approximately 10% of reproductive-age women with a high recurrence rate, but lacks reliable biomarkers. No previous studies have investigated the possible use of extracellular vesicle (EV)-associated micro RNAs (miRNAs) from menstrual blood (MB) as candidate diagnostic or prognostic markers of EM.Methods: Specimens were obtained from endometriosis and non-endometriosis patients at the International Peace Maternity and Child Health Hospital in Shanghai. Microarray was used to screen differentially expressed miRNAs among peritoneal fluid (PF), fallopian tube fluid (FF), and MB. Dual-luciferase reporter gene assay was carried out to verify the relationship between miR-4443 and ACSS2. Cell proliferation and Transwell invasion assays were performed in vitro after intervention on miR-4443 and ACSS2 in hEM15A human endometrial stromal cells and primary human endometrial stromal cells (hESCs). Spearman correlation analysis, receiver operating characteristic (ROC) curve analysis, and survival analysis were applied to clinical data, including severity of symptoms and relapse of EM among EM patients.Results: EV-associated miR-4443 was abundant in MB of endometriosis patients. ACSS2 knockdown and miR-4443 overexpression promoted cell proliferation and migration via the PI3K/AKT pathway. miR-4443 levels in MB-EVs were positively correlated with the degree of dyspareunia (r=0.64; P< 0.0001) and dysmenorrhea (r=0.42; P< 0.01) in the endometriosis group. ROC curve analyses showed an area under the curve (AUC) of 0.741 (95% CI 0.624– 0.858; P< 0.05) for miR-4443 and an AUC of 0.929 (95% CI 0.880– 0.978; P< 0.05) for the combination of miR-4443 and dysmenorrhea.Conclusion: MB-derived EV-associated miR-4443 might participate in endometriosis development, thus providing a new candidate biomarker for the noninvasive prediction of endometriosis recurrence. Keywords: endometriosis, menstrual blood, biomarker, extracellular vesicles, miR-4443

Yingxiu Liang,1 Xiaohong Hou,1 Haoying Chen,1 Ruqing Yang,1 Ruina Wang,1 Ruotong Mao,1 Junzhao Zhao,1 Hui Chen,2 Jing Cheng1 1Reproductive Center, Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325088, People’s Republic of China; 2School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, 2007, AustraliaCorrespondence: Jing Cheng, Reproductive Center, Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, No. 306 Hualongqiao Road, Lucheng District, Wenzhou, Zhejiang Province, 325088, People’s Republic of China, Tel +86 13780193700, Fax +86 57788002304, Email jingchengdoc_gyn@hotmail.com Hui Chen, Faculty of Science, University of Technology Sydney, No. 15 of Broadway, Ultimo, New South Wales, 2007, Australia, Tel/Fax +61 295141328, Email chenhuimind@sina.comObjective: Additive human menopausal gonadotropin (HMG)/recombinant luteinizing hormone (r-LH) to follicle-stimulating hormone (FSH) can improve pregnancy outcomes in patients with poor ovarian response during assisted reproductive procedures. However, their effects on patients with normal ovarian response during such procedures are unclear, which formed the aim of this study.Methods: This retrospective study enrolled 456 infertile women who underwent in vitro fertilization or intracytoplasmic sperm injection treatment. Group 1 received FSH; Group 2 received FSH+HMG/r-LH; Group 3 received FSH+HMG+r-LH.Results: The age and Body Mass Index were significantly greater in Group III. The endometrial thickness was greater in Groups II and III, suggesting better endometrial receptivity. Better pregnancy and birth outcomes were seen in Group 3. In sub-cohorts of women older than 32 years old or with overweight/obesity, pregnancy and birth outcomes were also much better in Group 3, albeit without statistical significance.Conclusion: The addition of both HMG and r-LH to FSH may improve the chance of infertile women with normal ovarian responses to have more success in having live birth babies, specifically in those over 32 years of age or with overweight/obese patients who typically face challenges in conceiving and sustaining a pregnancy.Keywords: in vitro fertilization, intracytoplasmic sperm injection, live birth rate, cumulative live birth rate

Yuling Liang,1,&ast; Yuqing Xie,1,&ast; Xiaoli Liu,1 Lihua Yu,1 Huiwen Yan,1 Zimeng Shang,1 Yuan Wu,1 Xue Cai,2 Wanxin Shi,2 Juan Du,3 Zhiyun Yang1 1Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 2Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 3Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Du, Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Email duj656@163.com Zhiyun Yang, Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China, Tel +86-10-84322148, Email yangzhiyun2016@163.comPurpose: Traditional Chinese medicine (TCM) therapy is an important means to treat hepatocellular carcinoma (HCC), Astragalus (Latin name: Hedysarum Multijugum Maxim; Chinese name: Huangqi, HQ) and Atractylodes (Latin name: Atractylodes Macrocephala Koidz; Chinese name: Baizhu, BZ) (HQBZ), a classic herb pair, is often used in combination to HCC. However, the main components and potential mechanisms of HQBZ therapy in HCC remain unclear. This study aimed to identify the potential active ingredients and molecular mechanisms of action of HQBZ in HCC treatment.Methods: The HQBZ-Compound-Target-HCC network and HQBZ-HCC transcriptional regulatory network were constructed to screen the core active compound components and targets of HQBZ therapy for HCC. Molecular docking techniques are used to verify the stability of binding core active compound components to targets. GO and KEGG enrichment analysis were used to explore the signaling pathway of HQBZ in HCC treatment, the mechanism of HQBZ treatment of HCC was verified based on in vivo H22 tumor bearing mice and in vitro cell experiments.Results: Network pharmacology and molecular docking studies showed that HQBZ treatment of HCC was related to the targeted regulation of IL-6 and STAT3 by the active compound biatractylolide, KEGG pathway enrichment analysis suggest that HQBZ may play a role in the treatment of HCC through IL-6/STAT3 signaling pathway. In vitro experiment results proved that HQBZ could regulate IL-6/STAT3 signaling pathway transduction on CD8+T cells, inhibit CD8+T cell exhaustion and restore the function of exhausted CD8+T cells. In vivo experiment results proved that HQBZ can regulate IL-6/STAT3 signaling pathway transduction in H22 liver cancer model mouse tumor tissue, increased the proportion of tumor infiltrating CD8+T cells.Conclusion: This study found that HQBZ may play a therapeutic role in HCC by targeting IL-6 and STAT3 through biatractylolide, its mechanism of action is related to regulating IL-6/STAT3 signaling pathway, reversing T cell failure and increasing tumor infiltration CD8+T cells.Keywords: Astragalus–Atractylodes herb pair, hepatocellular carcinoma, IL-6/STAT3 signaling pathway, molecular docking, network pharmacology

Wanxin Shi,1,2,&ast; Huiwen Yan,1,&ast; Xiaoli Liu,1 Lihua Yu,1 Yuqing Xie,1 Yuan Wu,1 Yuling Liang,1 Zhiyun Yang1 1Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2First Clinical Medical College, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiyun Yang, Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People’s Republic of China, Tel/Fax +86-10-84322148, Email yangzhiyun2016@163.comPurpose: Portal vein tumor thrombosis (PVTT) is one of the hallmarks of advanced Hepatocellular carcinoma (HCC). Platelet (PLT) function parameters and CD8+T cells (CD8+Ts) play an important role in HCC progression and metastasis. This study is committed to establishing an efficient prognosis prediction model and exploring the combined effect of PLT and CD8+Ts on PVTT prognosis.Patients and Methods: This retrospective study collected 932 HCC patients with PVTT from 2007 to 2017 and randomly divided them into a training cohort (n = 656) and a validation cohort (n = 276). We performed multivariable Cox and Elastic-net regression analysis, constructed a nomogram and used Kaplan–Meier survival curves to compare overall survival and progression-free survival rates in different substrata. Relationships between indicators involved were also analyzed.Results: We found tumor number, size, treatment, PLT, γ-glutamyl transferase, alpha-fetoprotein, mean platelet volume, and CD8+Ts were related to the 5-year OS of patients with PVTT, and established a nomogram. The area under the receiver operating characteristic curve (AUCs) for predicting the 1-year OS rates were 0.767 and 0.794 in training and validation cohorts. The calibration curve and decision curve indicated its predictive consistency and strong clinical utility. We also found those with low PLT (< 100&ast;10^9/L) and high CD8+Ts (> 320 cells/μL) had a better prognosis.Conclusion: We established a well-performing prognostic model for PVTT based on platelet functional parameters and CD8+Ts, and found that PT-8 formed by PLT and CD8+Ts was an excellent predictor of the prognosis of PVTT.Keywords: hepatocellular carcinoma, portal vein tumor thrombus, platelet, CD8+T cells counts, prognostic model, correlation analysis

Enhao Huang,1,2,&ast; Huadao Li,2,3,&ast; Hanghang Han,1,2,&ast; Lianshan Guo,4 Yubing Liang,3 Zijin Huang,1 Ke Qin,5 Xueke Du1 1Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530007, People’s Republic of China; 2Key Laboratory for Basic Science and Prevention of Perioperative Organ Dysfunction, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 3Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China; 4Department of Emergency, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530007, People’s Republic of China; 5Guilin People’s Hospital, Guilin, Guangxi Zhuang Autonomous Region, 541100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Qin; Xueke Du, Email qinke303@163.com; duxueke@gxmu.edu.cnPurpose: The primary objective of this study was to develop an innovative nanomedicine-based therapeutic strategy to alleviate Postoperative Neurocognitive Disorder (PND) in patients undergoing surgery.Patients and Methods: To achieve this goal, polydopamine-coated Kaempferol-loaded Metal-Organic Framework nanoparticles (pDA/KAE@ZIF-8) were synthesized and evaluated. The study involved encapsulating Kaempferol (KAE) within ZIF-8 nanoparticles, followed by coating with polydopamine (PDA) to enhance biocompatibility and targeted delivery. The characterization of these nanoparticles (NPs) was conducted using various techniques including Scanning Electron Microscopy, Fourier-Transform Infrared Spectroscopy, X-ray Diffraction, and Ultraviolet-Visible spectroscopy. The efficacy of pDA/KAE@ZIF-8 NPs was tested in both in vitro and in vivo models, specifically focusing on their ability to penetrate the blood-brain barrier and protect neuronal cells against oxidative stress.Results: The study found that pDA/KAE@ZIF-8 NPs efficiently penetrated the blood-brain barrier and were significantly taken up by neuronal cells. These nanoparticles demonstrated remarkable Reactive Oxygen Species (ROS) scavenging capabilities and stability under physiological conditions. In vitro studies showed that pDA/KAE@ZIF-8 NPs provided protection to HT-22 neuronal cells against H2O2-induced oxidative stress, reduced the levels of pro-inflammatory cytokines, and decreased apoptosis rates. In a PND mouse model, the treatment with pDA/KAE@ZIF-8 NPs significantly improved cognitive functions, surpassing the effects of KAE alone. This improvement was substantiated through behavioral tests and a noted reduction in hippocampal inflammation.Conclusion: The findings from this study underscore the potential of pDA/KAE@ZIF-8 NPs as an effective nanotherapeutic agent for PND. This approach offers a novel direction in the postoperative care of elderly patients, with the potential to transform the therapeutic landscape for neurocognitive disorders following surgery. The application of nanotechnology in this context opens new avenues for more effective and targeted treatments, thereby improving the quality of life for patients suffering from PND.Keywords: nanomedicine, reactive oxygen species, blood-brain barrier

Zhihao Zhao,1,&ast; Diya Qi,1,&ast; Zeqing Zhang,2,&ast; Xin Du,3 Fengyun Zhang,2 Ruicong Ma,4 Yi Liang,1 Yuewu Zhao,1 Ying Gao,1 Yu Yang2 1Department of Cardiology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou, People’s Republic of China; 2Department of Cardiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Department of Neurology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou, People’s Republic of China; 4Graduate School, Dalian Medical University, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Gao, Department of Cardiology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou, People’s Republic of China, Tel +86-13951461302, Email xzyygaoying@163.com Yu Yang, Department of Cardiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China, Tel +86-15651359875, Email xuzhouyangyu@163.comPurpose: The aim of this study was to explore the relationship between inflammatory cytokines and the risk of heart failure (HF) readmission in patients with heart failure with preserved ejection fraction (HFpEF).Patients and Methods: We enrolled 429 patients with HFpEF admitted to the cardiology department in our hospital from January 2020 to July 2022. The patients were divided into the readmission or non-readmission groups according to whether they were readmitted for heart failure within 1 year of discharge. The clinical features and laboratory date of the subjects were collected and analyzed. Multivariate cox regression analysis was used to identify predictors of HF readmission. In addition, receiver operating characteristic (ROC) curves were used to determine the prognostic value of each factor.Results: The levels of IL-1β, IL-6, IL-10, IL-17, TNF-α, NT-proBNP, heart rate, total cholesterol and NYHA class were significantly higher in the readmission group than in the non-readmission group (p < 0.05). IL-1β, IL-6, IL-17, TNF-α, NT-proBNP, heart rate and NYHA class were identified as independent predictors of HF readmission.Conclusion: Inflammatory markers, including IL-1β, IL-6, IL-17 and TNF-α were related to the HF readmission in patients with HFpEF.Keywords: heart failure with preserved ejection fraction, inflammation, cytokine, readmission, risk assessment

Yifan Liu,1 Yushan Liang,2 Jing Yuhong,3 Peng Xin,1 Jia Li Han,4 Yongle Du,5 Xinru Yu,3 Runhe Zhu,6 Mingxun Zhang,6 Wen Chen,7 Yingjie Ma7 1School of Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2School of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 3School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 4School of Health Sciences, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 5School of Ophthalmology and Optometry, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 6School of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 7First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Yingjie Ma; Wen Chen, The First Clinical College, Shandong University of Traditional Chinese Medicine; Reproductive and Genetic Center of Integrative Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 42, Wenhua Road (W), Lixia District, Jinan, 250014, People’s Republic of China, Email 545914553@qq.com; wenchen0515@163.comAbstract: This manuscript offers a comprehensive overview of nanotechnology’s impact on the solubility and bioavailability of poorly soluble drugs, with a focus on BCS Class II and IV drugs. We explore various nanoscale drug delivery systems (NDDSs), including lipid-based, polymer-based, nanoemulsions, nanogels, and inorganic carriers. These systems offer improved drug efficacy, targeting, and reduced side effects. Emphasizing the crucial role of nanoparticle size and surface modifications, the review discusses the advancements in NDDSs for enhanced therapeutic outcomes. Challenges such as production cost and safety are acknowledged, yet the potential of NDDSs in transforming drug delivery methods is highlighted. This contribution underscores the importance of nanotechnology in pharmaceutical engineering, suggesting it as a significant advancement for medical applications and patient care.Keywords: nanotechnology, solubility and bioavailability, poorly soluble drugs, drug delivery systems, pharmaceutical engineering

Meng-Ru Zhang,1,2,&ast; Lin-Lin Fang,3,&ast; Yang Guo,1 Qin Wang,1 You-Jie Li,1 Hong-Fang Sun,1 Shu-Yang Xie,1 Yan Liang1 1Department of Biochemistry and Molecular Biology, School of Basic Medicine, Binzhou Medical University, YanTai, ShanDong, 264003, People’s Republic of China; 2Department of Clinical Medicine, Binzhou Medical University, YanTai, ShanDong, 264003, People’s Republic of China; 3RemeGen Co., Ltd, YanTai, ShanDong, 264000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Liang; Shu-Yang Xie, Department of Biochemistry and Molecular Biology, School of Basic Medicine, Binzhou Medical University, YanTai, ShanDong, 264003, People’s Republic of China, Tel/Fax +86 535 6913335 ; +86 535 6913166, Email 18766567201@163.com; xieshuyang@bzmc.edu.cnAbstract: Cancer immunotherapy has emerged as a novel therapeutic approach against tumors, with immune checkpoint inhibitors (ICIs) making significant clinical practice. The traditional ICIs, PD-1 and PD-L1, augment the cytotoxic function of T cells through the inhibition of tumor immune evasion pathways, ultimately leading to the initiation of an antitumor immune response. However, the clinical implementation of ICIs encounters obstacles stemming from the existence of an immunosuppressive tumor microenvironment and inadequate infiltration of CD8+T cells. Considerable attention has been directed towards advancing immunogenic cell death (ICD) as a potential solution to counteract tumor cell infiltration and the immunosuppressive tumor microenvironment. This approach holds promise in transforming “cold” tumors into “hot” tumors that exhibit responsiveness to antitumor. By combining ICD with ICIs, a synergistic immune response against tumors can be achieved. However, the combination of ICD inducers and PD-1/PD-L1 inhibitors is hindered by issues such as poor targeting and uncontrolled drug release. An advantageous solution presented by stimulus-responsive nanocarrier is integrating the physicochemical properties of ICD inducers and PD-1/PD-L1 inhibitors, facilitating precise delivery to specific tissues for optimal combination therapy. Moreover, these nanocarriers leverage the distinct features of the tumor microenvironment to accomplish controlled drug release and regulate the kinetics of drug delivery. This article aims to investigate the advancement of stimulus-responsive co-delivery nanocarriers utilizing ICD and PD-1/PD-L1 inhibitors. Special focus is dedicated to exploring the advantages and recent advancements of this system in enabling the combination of ICIs and ICD inducers. The molecular mechanisms of ICD and ICIs are concisely summarized. In conclusion, we examine the potential research prospects and challenges that could greatly enhance immunotherapeutic approaches for cancer treatment.Keywords: antitumor therapy, immunogenic cell death, co-delivery, immune-checkpoint inhibitors, stimulus-responsive nanocarriers

Zhengyi Lyu,1,&ast; Qiongying Shen,1,&ast; Shuxin Tian,1,&ast; Liyan Gong,2 Haizhou Lou,3 Guanai Bao,2 Zhuoxuan Wu,3 Chao Lu,2 Weiping Zhang,4 Rui Huang,5 Conghua Ji,6 Siyi Zheng,1 Wei Pan,1 Yinyin Ying,4 Jianwei Jin,4 Yi Liang4 1The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Medical Oncology, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Acupuncture, the Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 5Department of Acupuncture and Tuina, Wenzhou Central Hospital, Wenzhou, Zhejiang, People’s Republic of China; 6Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Liang, Department of Acupuncture, the Third Affiliated Hospital of Zhejiang Chinese Medical University, 219 Moganshan Road, Hangzhou City, Zhejiang Province, 310053, People’s Republic of China, Email liangyiwww@126.comBackground: Transcutaneous Electrical Acupoint Stimulation (TEAS) therapy opens up the possibility for individuals with Cancer-induced bone pain (CIBP) to receive a home-based, patient-controlled approach to pain management. The aim of this study is designed to evaluate the efficacy of patient-controlled TEAS (PC-TEAS) for relieving CIBP in patients with non-small cell lung cancer (NSCLC).Methods/Design: This is a study protocol for a prospective, triple-blind, randomized controlled trial. We anticipate enrolling 188 participants with NSCLC bone metastases who are also using potent opioid analgesics from 4 Chinese medical centers. These participants will be randomly assigned in a 1:1 ratio to either the true PC-TEAS or the sham PC-TEAS group. All participants will receive standard adjuvant oncology therapy. The true group will undergo patient-controlled TEAS intervention as needed, while the sham group will follow the same treatment schedule but with non-conductive gel patches. Each treatment course will span 7 days, with a total of 4 courses administered. There will be 4 assessment time points: baseline, the conclusion of weeks 4, 8, and 12. The primary outcome of this investigation is the response rate of the average pain on the Brief Pain Inventory (BPI) scale at week 4 after treatment. Secondary outcomes include pain related indicators, quality of life scale, mood scales, and routine blood counts on the assessment days. Any adverse events will be promptly addressed and reported if they occur. We will manage trial data using the EDC platform, with a data monitoring committee providing regular quality oversight.Discussion: PC-TEAS interventions offer an attempt to achieve home-based acupuncture treatment and the feasibility of achieving triple blinding in acupuncture research. This study is designed to provide more rigorous trial evidence for the adjuvant treatment of cancer-related pain by acupuncture and to explore a safe and effective integrative medicine scheme for CIBP.Trial Registration: ClinicalTrials.gov NCT05730972, registered February 16, 2023.Keywords: bone cancer pain, TEAS, transcutaneous electrical nerve stimulation, patient-controlled analgesia, integrative medicine, home-based treatment

Huan-Huan Shen,1,2,&ast; Jie-Fei Peng,1,3,&ast; Ran-Ran Wang,4,&ast; Ping-Yu Wang,1,5 Jia-Xiang Zhang,1 Hong-Fang Sun,1 Yan Liang,1 Yan-Mei Li,6 Jiang-Nan Xue,7 You-Jie Li,1 Guang-Bin Sun,1,&ast; Shu-Yang Xie1,2,&ast; 1Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, Shandong, 264003, People’s Republic of China; 2Shandong Laboratory of Advanced Materials and Green Manufacturing, Yantai, Shandong, 264000, People’s Republic of China; 3Department of Clinical Laboratory, the Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, People’s Republic of China; 4Institute of Rehabilitation Medicine, School of Rehabilitation Medicine, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China; 5Department of Epidemiology, Binzhou Medical University, YanTai, ShanDong, 264003, People’s Republic of China; 6Department of Immune Rheumatism, Yantaishan Hospital, Yantai, Shandong, 264000, People’s Republic of China; 7Department of Immunology, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shu-Yang Xie; Guang-Bin Sun, Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, Shandong, 264003, People’s Republic of China, Tel +86 535 6913010 ; +86 535 6913335, Fax +86 535 6913163, Email xieshuyang@bzmc.edu.cn; bingo@bzmc.edu.cnPurpose: The drug resistance and low response rates of immunotherapy limit its application. This study aimed to construct a new nanoparticle (CaCO3-polydopamine-polyethylenimine, CPP) to effectively deliver interleukin-12 (IL-12) and suppress cancer progress through immunotherapy.Methods: The size distribution of CPP and its zeta potential were measured using a Malvern Zetasizer Nano-ZS90. The morphology and electrophoresis tentative delay of CPP were analyzed using a JEM-1400 transmission electron microscope and an ultraviolet spectrophotometer, respectively. Cell proliferation was analyzed by MTT assay. Proteins were analyzed by Western blot. IL-12 and HMGB1 levels were estimated by ELISA kits. Live/dead staining assay was performed using a Calcein-AM/PI kit. ATP production was detected using an ATP assay kit. The xenografts in vivo were estimated in C57BL/6 mice. The levels of CD80+/CD86+, CD3+/CD4+ and CD3+/CD8+ were analyzed by flow cytometry.Results: CPP could effectively express EGFP or IL-12 and increase ROS levels. Laser treatment promoted CPP-IL-12 induced the number of dead or apoptotic cell. CPP-IL-12 and laser could further enhance CALR levels and extracellular HMGB1 levels and decrease intracellular HMGB1 and ATP levels, indicating that it may induce immunogenic cell death (ICD). The tumors and weights of xenografts in CPP-IL-12 or laser-treated mice were significantly reduced than in controls. The IL-12 expression, the CD80+/CD86+ expression of DC from lymph glands, and the number of CD3+/CD8+T or CD3+/CD4+T cells from the spleen increased in CPP-IL-12-treated or laser-treated xenografts compared with controls. The levels of granzyme B, IFN-γ, and TNF-α in the serum of CPP-IL-12-treated mice increased. Interestingly, CPP-IL-12 treatment in local xenografts in the back of mice could effectively inhibit the growth of the distant untreated tumor.Conclusion: The novel CPP-IL-12 could overexpress IL-12 in melanoma cells and achieve immunotherapy to melanoma through inducing ICD, activating CD4+ T cell, and enhancing the function of tumor-reactive CD8+ T cells.Keywords: cancer immunotherapy, CaCO3 nanoparticle, interleukin-12, immunogenic cell death, tumor therapy

Yuxin Liang,1,&ast; Deyuan Zhong,1,&ast; Qinyan Yang,1 Yuan Tang,1 Yingying Qin,2 Yuhao Su,1 Xiaolun Huang,1 Jin Shang1 1Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Macau, SAR, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jin Shang; Xiaolun Huang, Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China, Email 935516165@qq.com; huangxiaolun@med.uestc.edu.cnBackground: Tumor metastasis is the leading cause of high mortality in hepatocellular carcinoma (HCC). The metastasis-related HCC microenvironment is characterized by high heterogeneity. Single-cell RNA sequencing (scRNA-seq) may aid in determining specific cell clusters involved in regulating the immune microenvironment of HCC.Methods: The scRNA-seq data of 10 HCC samples were collected from the Gene Expression Omnibus (GEO) database GSE124395. Correlations between key gene expression and clinicopathological data were determined using public databases. HCC tissues and matched tumor-adjacent and normal tissue samples were obtained by surgical resection at Sichuan Cancer Hospital. Immune cell infiltration analysis was performed and verified by immunohistochemistry and immunofluorescent staining.Results: Nine malignant hepatocyte clusters with different marker genes and biological functions were identified. C3_Hepatocyte-SERF2 and C6_Hepatocyte-IL13RA2 were mainly involved in the regulation of the immune microenvironment, which was also a significant pathway in regulating HCC metastasis. Key genes in malignant hepatocyte clusters that associated with HCC metastasis were further screened by LASSO regression analysis. TPI1, a key gene in C6_Hepatocyte-IL13RA2 and HCC metastasis, could participate in regulating the HCC immune microenvironment in The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMER) databases. Moreover, immunohistochemistry analysis demonstrated that TPI1 expression was positively correlated with HCC metastasis and poor prognosis, while negatively correlated with CD8+ T cell infiltration. The negative correlation between TPI1 expression and CD8+ T cell infiltration was further confirmed by immunofluorescence staining.Conclusion: In summary, a cluster of TPI1+ malignant hepatocytes was associated with the suppression of CD8+ T cell infiltration and HCC metastasis, providing novel insights into potential biomarkers for immunotherapy in HCC.Keywords: single-cell RNA sequencing, malignant hepatocyte, hepatocellular carcinoma, immune microenvironment, metastasis

Caining Wen,1,&ast; Xiao Xu,1,&ast; Yuanmin Zhang,1 Jiang Xia,2 Yujie Liang,1,3 Limei Xu1 1Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, People’s Republic of China; 2Department of Chemistry, the Chinese University of Hong Kong, Shatin, Hong Kong SAR, People’s Republic of China; 3Engineering Research Center of Intelligent Rehabilitation, College of Rehabilitation Medicine, Jining Medical University, Jining, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yujie Liang; Limei Xu, Email liangyjie@126.com; xulm2014@163.comAbstract: Osteoporosis (OP) affects millions of people worldwide, especially postmenopausal women and the elderly. Although current available anti-OP agents can show promise in slowing down bone resorption, most are not specifically delivered to the hard tissue, causing significant toxicity. A bone-targeted nanodrug delivery system can reduce side effects and precisely deliver drug candidates to the bone. This review focuses on the progress of bone-targeted nanoparticles in OP therapy. We enumerate the existing OP medications, types of bone-targeted nanoparticles and categorize pairs of the most common bone-targeting functional groups. Finally, we summarize the potential use of bone-targeted nanoparticles in OP treatment. Ongoing research into the development of targeted ligands and nanocarriers will continue to expand the possibilities of OP-targeted therapies into clinical application. Keywords: bone targeting, nanomedicine, osteoporosis therapy

Jiemei Ye,1,2,&ast; Xiaoying Huang,3,4,&ast; Weiling Qin,1,2,&ast; Pan Liang,3,4 Jun Zhao,4 Yinxin Ye,1,2 Huojin Ji,1,2 Xinyun Peng,1,2 Yushan Liang,3,4 Yonglin Cai1,5 1Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, People’s Republic of China; 2Department of Clinical Laboratory, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, People’s Republic of China; 3Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 5Department of Preventive Medicine, Wuzhou Cancer Center, Wuzhou, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonglin Cai, Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, Guangxi, 543002, People’s Republic of China, Email cylzen@163.com Yushan Liang, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email yushanliang33@outlook.comPurpose: Paired Box 5 (PAX5) is a transcription factor that is widely associated with carcinogenesis. PAX5 can maintain Epstein-Barr virus (EBV) latency in B cells, while a close association exists between EBV infection and nasopharyngeal carcinoma (NPC). However, there are very few reports on the correlation between PAX5 and NPC development. The aim of this study was to investigate the role of PAX5 in NPC.Patients and Methods: The clinical value and prognostic significance of PAX5 in NPC and the association with PAX5 expression and immune cell infiltration were analyzed by multiple GEO datasets. In vivo and in vitro experiments including real-time PCR, Western blot, CCK-8 assay, and methylation sequencing were used to validate the results of bioinformatics analysis.Results: The expression of PAX5 was significantly reduced in NPC tissues, with the low expression being correlated with advanced clinical stage, low tumor mutation burden and immune activation, high relative expression of EBV, poor survival for NPC patients. PAX5 exhibited excellent diagnostic performance and had potential as a predictive factor for response to the immune checkpoint inhibitors therapy. Enrichment analysis suggested that the low expression of PAX5 was associated with the dysregulation of Hippo and Wnt signaling pathways. The promoter of PAX5 gene was hypermethylated in NPC tissues. Furthermore, the in vitro and in vivo experiments revealed that NPC tissue and cell lines had low mRNA expression levels of PAX5, the PAX5 promoter was hypermethylated in NPC cell lines, and PAX5 overexpression inhibited NPC cell proliferation and tumor growth in nude mice.Conclusion: PAX5 may be a tumor suppressor and serve as a novel potential diagnostic and prognostic marker for NPC.Keywords: nasopharyngeal carcinoma, transcription factor, PAX5, prognosis, immunity, Epstein-Barr virus

Ruijia Liu,1,2,&ast; Xudong Yu,1,&ast; Xu Cao,1,2 Xuyun Wang,3 Yijun Liang,2 Wenying Qi,1,2 Yong’an Ye,1,2 Xiaobin Zao1,2,4 1Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, People’s Republic of China; 2Institute of Liver Diseases, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, People’s Republic of China; 3Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 4Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaobin Zao, Assistant Researcher, Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, 5 Haiyuncang Road, Dongcheng District, Beijing, 100700, People’s Republic of China, Tel +86-10-8401-3194, Email A3417@bucm.edu.cnPurpose: ST6 Beta-Galactoside Alpha-2,6-Sialyltransferase 2 (ST6GAL2), a member of the sialic acid transferase family, is differentially expressed in diverse cancers. However, it remains poorly understood in tumorigenesis and impacts on immune cell infiltration (ICI) in hepatocellular carcinoma (HCC).Patients and Methods: Herein, the expression, diagnosis, prognosis, functional enrichment, genetic alterations, immune characteristics, and targeted drugs of ST6GAL2 in HCC were researched by conducting bioinformatics analysis, in vivo, and in vitro experiments.Results: ST6GAL2 was remarkably decreased in HCC compared to non-tumor tissues, portending a poor prognosis associated with high DNA methylation levels. Functional enrichment and GSVA analyses revealed that ST6GAL2 might function through the extracellular matrix, PI3K-Akt signaling pathways, and tumor inflammation signature. We found that ST6GAL2 expression was proportional to ICI, immunostimulator, and immune subtypes. ST6GAL2 expression first increased and then decreased during the progression of liver inflammation to HCC. The dysfunctional experiment indicated that ST6GAL2 might exert immunosuppressive effects during HCC progression through regulating ICI. Several broad-spectrum anticancer drugs were obtained by drug sensitivity prediction analysis of ST6GAL2.Conclusion: In conclusion, ST6GAL2 was a reliable prognostic biomarker strongly associated with ICI, and could be a potential immunotherapeutic target for HCC.Keywords: hepatocellular carcinoma, ST6GAL2, prognosis, immune cell infiltration, biomarker

Yufei Liang,1 Lina Mei,2 Qipeng Ning,2 Jiao Zhang,2 Jingying Fei,3 Jie Dong1 1Department of Gynaecology and Obstetrics, Huzhou Maternity & Child Health Care Hospital, Huzhou, People’s Republic of China; 2Department of Digestive, Huzhou Maternity & Child Health Care Hospital, Huzhou, People’s Republic of China; 3Department of Ultrasound, Huzhou Maternity & Child Health Care Hospital, Huzhou, People’s Republic of ChinaCorrespondence: Jie Dong, Department of Gynaecology and Obstetrics, Huzhou Maternity & Child Health Care Hospital, No. 2 East Street, Wuxing District, Huzhou City, Zhejiang Province, People’s Republic of China, Email 94276941@qq.comBackground: Endometriosis involves the intestine, and its clinical manifestations are nonspecific and lack of etiological manifestations. The diagnosis is difficult, which often leads to misdiagnosis. We report a case of endometriosis which was misdiagnosed as intestinal malignant tumor after colonoscopy and three biopsies.Case Presentation: We reported a 42-year-old woman who went to see a doctor because of anal distension. She was examined by three gastrointestinal endoscopists at different levels in different hospitals and underwent biopsy at the same time. Combined with clinical manifestations, imaging examination, endoscopic examination and pathological examination, she was misdiagnosed as intestinal malignant tumor, and partial intestinal resection was performed according to the surgical principle of malignant tumor.Conclusion: Although there are advanced gastrointestinal endoscopy and imaging techniques, intestinal endometriosis is still easy to be misdiagnosed. As our case report shows, after three colonoscopy and biopsy, it is still misdiagnosed as intestinal malignant tumor. Further research is needed to improve the ability of preoperative diagnosis, which deserves the attention of gastroenterologists and obstetricians and gynecologists.Keywords: endometriosis, intestinal malignant tumor, colonoscopy

Ye Liang,1– 4,&ast; Bing Wang,1– 4,&ast; Qing Yu,1– 4 Weijia Wang,1– 4 Shaohua Ge,1– 4 Jinlong Shao1– 4 1Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, 250012, People’s Republic of China; 2Shandong Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, 250012, People’s Republic of China; 3Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, 250012, People’s Republic of China; 4Shandong Provincial Clinical Research Center for Oral Diseases, School of Stomatology, Shandong University, Jinan, 250012, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaohua Ge; Jinlong Shao, Tel +86 531 88382123 ; +86 531 88382597, Fax +86 531 88382923, Email shaohuage@sdu.edu.cn; jinlong.shao@sdu.edu.cnObjective: Silver nanoparticles (AgNPs) possess excellent antibacterial effects on periodontal pathogens, but their clinical application is limited mainly due to their cytotoxicity through inducing oxidative stress in human cells. Ebselen disrupts the reactive oxygen species (ROS) scavenging in bacteria and relieves oxidative stress in mammalian cells. This study aimed to assess the antibacterial and anti-inflammatory effects of AgNPs and ebselen as well as the protective effect of ebselen, to further provide the theoretical basis for their future application in periodontal treatment.Methods: The antibacterial and anti-biofilm effects of the synthesized AgNPs combined with ebselen were assessed on Porphyromonas gingivalis (P. gingivalis), Streptococcus gordonii (S. gordonii), and Fusobacterium nucleatum (F. nucleatum) in planktonic condition and as biofilms. In addition, the intracellular bactericidal efficiency of AgNPs and ebselen was evaluated in P. gingivalis-infected human gingival fibroblasts (HGFs). The cytotoxicity, intracellular ROS levels, and potential antioxidative enzymes were detected in HGFs treated with AgNPs and ebselen. Further, the anti-inflammatory effects were evaluated by in vitro and in vivo experiments.Results: The combination of AgNPs and ebselen showed excellent antibacterial effects against planktonic P. gingivalis and F. nucleatum and synergistic antibiofilm effects on all mono- and multi-species biofilms. In addition, ebselen significantly enhanced the intracellular bactericidal efficiency of AgNPs. Furthermore, ebselen combined with up to 20 μg/mL AgNPs showed no obvious cytotoxicity to HGFs. Evidently, ebselen alleviated the AgNPs-induced ROS by increasing the levels of glutathione and superoxide dismutase 2. Moreover, AgNPs and ebselen together declined the release of P. gingivalis-stimulated inflammatory cytokines both in vitro and in vivo, and reduced alveolar bone resorption effectively.Conclusion: AgNPs combined with ebselen would be an effective adjuvant for periodontal treatment owing to their synergistic antibacterial and anti-inflammatory effects. Keywords: periodontitis, antibacterial, oxidative stress, anti-inflammation

Yan Fang,1,2,&ast; Chuang Xiao,1,&ast; Lueli Wang,1,&ast; Youlan Wang,3 Jun Zeng,1 Yaping Liang,1 Rong Huang,1 Yunke Shi,2 Sha Wu,1 Xiaohua Du,2 Shibo Sun,2 Min Li,2 Yuanyuan Zheng,2 Hongxiang Wu,1 Qiuzhe Guo,4 Weimin Yang1 1School of Pharmaceutical Science and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, People’s Republic of China; 2The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Kunming Institute of Medical Sciences, Kunming, People’s Republic of China; 4Fuwai Yunnan Cardiovascular Hospital, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiuzhe Guo; Weimin Yang, Email drguoqz@163.com; ywmbessie@yeah.netBackground: Sepsis is initiated by the dysfunctional response of the host immune system to infection. Septic shock and acute lung injury (ALI) are the main etiology of death caused by sepsis. Glucocorticoids, which are commonly used in clinic to antagonize the inflammatory response of sepsis, may cause serious side effects. Isoforskolin (ISOF) from the plant Coleus forskohlii stimulates adenylyl cyclase, increases the cAMP level and inhibits inflammatory response. The aim of this study was to investigate the synergistic effect of ISOF with dexamethasone (DEX) to prevent and ameliorate septic inflammation.Methods: Lipopolysaccharide (LPS) of 30 and 5 mg/kg (iv.) was used to induce sepsis and ALI mice model respectively in vivo. BEAS-2B cells stimulated by LPS were applied as cell model in vitro. The cumulative survival of mice with LPS-induced sepsis and the histopathological changes of lungs in mice with acute lung injury were observed, and the secretion of pro-inflammatory cytokines was analyzed by ELISA. The expression of RGS2 in BEAS-2B cells was detected by immunoblotting assay and PCR.Results: In the sepsis mice model, ISOF (10 mg/kg) combined with DEX (10 mg/kg.) (ip.) pretreatment significantly increased mice survival rate from 33.3% to 58.3%, which was significantly higher than that of ISOF or DEX treated alone. In the ALI mice model, ISOF, DEX pretreatment alone and combined application attenuated pulmonary pathological changes in ALI mice. Furthermore, ISOF, DEX alone or combined administration decreased MPO, MDA, IL-6, and IL-8 levels, while significantly synergistic effects were observed in the combined treatment group compared with ISOF or DEX alone. In BEAS-2B cells, combined pretreatment with ISOF and DEX significantly decreased the expression of IL-8 and increased the expression of RGS2.Conclusion: The results indicated that ISOF in combination with DEX synergistically improves survival rate and attenuates ALI in mice model through anti-inflammatory and antioxidant effects.Keywords: isoforskolin, sepsis, acute lung injury, pulmonary inflammation, glucocorticoids, regulator of G-protein signaling 2

Xiuri Wang,1,&ast; Yunxiao Liang,1,&ast; Qiuchen Cheng,1 Wei Nong,1 Liuyang Hu2 1Department of Gastroenterology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530016, People’s Republic of China; 2Department of Laboratory Medicine, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liuyang Hu, Department of Laboratory Medicine, The People’s Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Taoyuan Road N 6, Nanning, Guangxi, 530016, People’s Republic of China, Email 1225432679@qq.comAbstract: Nocardiosis is mainly an opportunistic infection that affects immunosuppressed individuals, with the most common manifestation being the pulmonary infection and cerebral abscesses. Abdominal abscesses caused by Nocardia is rare in diabetes patients. Here, we report a rare case of abdominal abscesses caused by Nocardia farcinica (N. farcinica) in a 56-year-old man with poorly controlled type 2 diabetes and prolonged use of corticosteroids for the treatment of secondary adrenal insufficiency. Abdominal CT suggested abdominal abscesses, and the culture of the abscess puncture fluid identified it as N. farcinica by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Treatment with a combination of trimethoprim-sulfamethoxazole (TMP-SMX) and imipenem/cilastatin (IPM/CS), along with surgical drainage and reduction in corticosteroid dosage, achieved successful outcomes in treating disseminated abdominal abscesses. Immunocompromised patients with unexplained fever, abdominal pain, and abdominal abscess should be suspected of Nocardia infection.Keywords: abdominal nocardiosis, Nocardia farcinica, abdominal abscesses, diabetes, corticosteroid

Qiumei Lin,1,&ast; Zongwei Jiang,1,&ast; Dan Mo,2,&ast; Fengfei Liu,1 Yuling Qin,1 Yihua Liang,1 Yuchen Cheng,3 Hao Huang,1 Min Fang1,4 1Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Department of Breast, Guangxi Zhuang Autonomous Region Maternal and Child Health Care Hospital, Nanning, 530025, People’s Republic of China; 3Department of Clinical Laboratory, Wuzhou Maternal and Child Health-Care Hospital, Wuzhou, People’s Republic of China; 4Engineering Research Center for Tissue & Organ Injury and Repair Medicine, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Huang; Min Fang, Email 1057226867@qq.com; fangmin@sr.gxmu.edu.cnBackground: Accurate prognosis is crucial for improving hepatocellular carcinoma (HCC) patients, clinical management, and outcomes post-liver resection. However, the lack of reliable prognostic indicators poses a significant challenge. This study aimed to develop a user-friendly nomogram to predict HCC patients’ post-resection prognosis.Methods: We retrospectively analyzed the data from 1091 HCC patients, randomly split into training (n=767) and validation (n=324) cohorts. Receiver operating characteristic (ROC) curves determined the optimal cut-off value for alpha1-microglobulin (α 1MG) and Beta2-microglobulin (β 2MG). Kaplan–Meier analysis assessed microglobulin’s impact on survival, followed by Cox regression to identify prognostic factors and construct a nomogram. The predictive accuracy and discriminative ability of the nomogram were measured by the concordance index (C-index), calibration curves, area under the ROC curve (AUC), and decision curve analysis (DCA), and were compared with the BCLC staging system, Edmondson grade, or BCLC stage plus Edmondson grade.Results: Patients with high β 2MG (≥ 2.395mg/L) had worse overall survival (OS). The nomogram integrated β 2MG, BCLC stage, Edmondson grade, microvascular invasion (MVI), and serum carbohydrate antigen 199 (CA199) levels. C-index for training and validation cohorts (0.712 and 0.709) outperformed the BCLC stage (0.660 and 0.657), Edmondson grade (0.579 and 0.564), and the combination of BCLC stage with Edmondson grade (0.681 and 0.668), improving prognosis prediction. Calibration curves demonstrated good agreement between predicted and observed survival. AUC values exceeded 0.700 over time, highlighting the nomogram’s discriminative ability. DCA revealed superior overall net income compared to other systems, emphasizing its clinical utility.Conclusion: Our β 2MG-based nomogram accurately predicts HCC patients’ post-resection prognosis, aiding intervention and follow-up planning. Significantly, our nomogram surpasses existing prognostic indicators, including BCLC stage, Edmondson grade, and the combination of BCLC stage with Edmondson grade, by demonstrating superior predictive performance.Keywords: hepatocellular carcinoma, nomogram, microglobulin, prognosis

Jie Xiang,1 Liyan Qin,2 Jinling Zhong,3 Ning Xia,2 Yuzhen Liang3 1Department of Clinical Nutrition, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Geriatric Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Endocrinology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Yuzhen Liang, Department of Endocrinology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email liangyuzhen26@163.com Ning Xia, Department of Geriatric Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, Email xianing12@sina.comBackground: Obesity is related to the loss of skeletal muscle mass and function (sarcopenia). The co-existence of obesity and sarcopenia is called sarcopenic obesity (SO). Glucagon like peptide-1 receptor agonists (GLP-1RA) are widely used in the treatment of diabetes and obesity. However, the protective effects of GLP-1RA on skeletal muscle in obesity and SO are not clear. This study investigated the effects of GLP-1RA liraglutide and semaglutide on obesity-induced muscle atrophy and explored the underlying mechanisms.Methods: Thirty-six male C57BL/6J mice were randomly divided into two groups and fed a regular diet and a high-fat diet for 18 weeks, respectively. After establishing an obesity model, mice were further divided into six groups: control group, liraglutide (LIRA) group, semaglutide (SEMA) group, high-fat diet (HFD) group, HFD + LIRA group, HFD + SEMA group, and subcutaneous injection for 4 weeks. The body weight, muscle mass, muscle strength, glycolipid metabolism, muscle atrophy markers, myogenic differentiation markers, GLUT4 and SIRT1 were analyzed. C2C12 myotube cells treated with palmitic acid (PA) were divided into four groups: control group, PA group, PA + LIRA group, PA + SEMA group. The changes in glucose uptake, myotube diameter, lipid droplet infiltration, markers of muscle atrophy, myogenic differentiation markers, GLUT4 and SIRT1 were analyzed, and the changes in related indicators were observed after the addition of SIRT1 inhibitor EX527.Results: Liraglutide and semaglutide reduced HFD-induced body weight gain, excessive lipid accumulation and improved muscle atrophy. Liraglutide and semaglutide eliminated the increase of muscle atrophy markers in skeletal muscle and C2C12 myotubes. Liraglutide and semaglutide restored impaired glucose tolerance and insulin resistance. However, these beneficial effects were attenuated by inhibiting SIRT1 expression.Conclusion: Liraglutide and semaglutide protects skeletal muscle against obesity-induced muscle atrophy via the SIRT1 pathway.Keywords: liraglutide, semaglutide, muscle atrophy, obesity, insulin resistance, SIRT1

Yan Liang,1,2 Ping-Yu Wang,1 Ze-Yun Liu,3 Hong-Fang Sun,1 Qin Wang,1 Guang-Bin Sun,1 Xia Zhang,1 You-Jie Li,1 Shu-Yang Xie1,2 1Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, ShanDong, 264003, People’s Republic of China; 2Department of Physiology and Pathophysiology, School of Basic Medicine, Qingdao University, QingDao, ShanDong, 266071, People’s Republic of China; 3School of International Studies, Binzhou Medical University, YanTai, ShanDong, 264003, People’s Republic of ChinaCorrespondence: Shu-Yang Xie; You-Jie Li, Department of Biochemistry and Molecular Biology, Binzhou Medical University, YanTai, ShanDong, 264003, People’s Republic of China, Tel/Fax +86 535 6913166 ; Tel/Fax +86 535 6913335, Email shuyangxie@aliyun.com; youjie1979@163.comIntroduction: As the special modality of cell death, immunogenic cell death (ICD) could activate immune response. Phototherapy in combination with chemotherapy (CT) is a particularly efficient tumor ICD inducing method that could overcome the defects of monotherapies.Methods: In this study, new dual stimuli-responsive micelles were designed and prepared for imaging-guided mitochondrion-targeted photothermal/photodynamic/CT combination therapy through inducing ICD. A dual-sensitive methoxy-polyethylene glycol-SS-poly(L-γ-glutamylglutamine)-SS-IR780 (mPEG-SS-PGG-SS-IR780) polymer was synthesized by grafting IR780 with biodegradable di-carboxyl PGG as the backbone, and mPEG-SS-PGG-SS-IR780/paclitaxel micelles (mPEG-SS-PGG-SS-IR780/PTXL MCs) were synthesized by encapsulating PTXL in the hydrophobic core.Results: In-vivo and -vitro results demonstrated that the three-mode combination micelles inhibited tumor growth and enhanced the therapeutic efficacy of immunotherapy. The dual stimuli-responsive mPEG-SS-PGG-SS-IR780/PTXL MCs were able to facilitate tumor cell endocytosis of nanoparticles. They were also capable of promoting micelles disintegration and accelerating PTXL release. The mPEG-SS-PGG-SS-IR780/PTXL MCs induced mitochondrial dysfunction by directly targeting the mitochondria, considering the thermo- and reactive oxygen species (ROS) sensitivity of the mitochondria. Furthermore, the mPEG-SS-PGG-SS-IR780/PTXL MCs could play the diagnostic and therapeutic roles via imaging capabilities.Conclusion: In summary, this study formulated a high-efficiency nanoscale platform with great potential in combined therapy for tumors through ICD.Keywords: immunogenic cell death, photothermal/photodynamic/chemo therapy, dual-stimuli-responsive, poly(amino acid)s micelles, imaging-guided therapy, mitochondria targeting

Mu-Lan Xu,1,2,&ast; Xiang-Bo Wu,1,&ast; Ying Liang,3,&ast; Ning Li,1 Xu Hu,1 Xiao-Dong Lin,1 Miao-Qiao Sun,1 Chun-Qiu Dai,1 Dan Niu,1 Yan-Rong Zhang,1 Hui Cao,1 Chen-Guang Zhao,1 Xiao-Long Sun,1 Hua Yuan1 1Department of Rehabilitation Medicine, Xi-Jing Hospital, Air Force Medical University (Fourth Military Medical University), Xi’an, Shaanxi, People’s Republic of China; 2Department of Rehabilitation Medicine, Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Shanwei, Guangdong, People’s Republic of China; 3Department of Health Statistics, Air Force Medical University (Fourth Military Medical University), Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Yuan; Xiao-Long Sun, Department of Rehabilitation Medicine, Xi-Jing Hospital, Air Force Medical University (Fourth Military Medical University), No. 15, Changle West Road, Xi’an, Shaanxi, 710032, People’s Republic of China, Tel/Fax +86-29-84775437 ; +86-29-84775439, Email yuanhua@fmmu.edu.cn; xlsun@fmmu.edu.cnBackground: Neuropathic pain (NP) is a common and severe problem following spinal cord injury (SCI). However, its relationship with functional outcome remains unclear.Methods: A retrospective explorative analysis was performed on SCI patients admitted to a tertiary academic medical center between January 2018 and June 2022. The candidate predictor variables, including demographics, clinical characteristics and complications, were analyzed with logistic and linear regression. Spinal Cord Independence Measure (SCIM) scores at discharge and mean relative functional gain (mRFG) of SCIM were as outcome parameters.Results: A total of 140 SCI patients included for the final analysis. Among them, 44 (31.43%) patients were tetraplegics, and 96 (68.57%) patients were paraplegics; 68 (48.57%) patients developed NP, and 72 (51.43%) patients did not. Logistic and linear regression analyses of SCIM at discharge both showed that NP [OR=3.10, 95% CI (1.29,7.45), P=0.01; unstandardized β=11.47, 95% CI (4.95,17.99), P< 0.01; respectively] was significantly independent predictors for a favorable outcome (SCIM at discharge ≥ 50, logistic regression results) and higher SCIM total score at discharge (linear regression results). Besides, NP [unstandardized β=15.67, 95% CI (8.94,22.41), P< 0.01] was also independently associated with higher mRFG of SCIM scores. Furthermore, the NP group had significantly higher mRFG, SCIM total scores and subscales (self-care, respiration and sphincter management, and mobility) at discharge compared to the non-NP group. However, there were no significant differences in mRFG, SCIM total score or subscales at discharge among the NP subgroups in terms of locations (at level pain, below level pain, and both) or timing of occurrence (within and after one month after SCI). This study also showed that incomplete injury, lumbar-sacral injury level and non-anemia were significantly independent predictors for a favorable outcome, and higher mRFG of SCIM scores (except for non-anemia).Conclusion: NP appears independently associated with better functional recovery in SCI patients, suggesting the bright side of this undesirable complication. These findings may help to alleviate the psychological burden of NP patients and ultimately restore their confidence in rehabilitation.Keywords: spinal cord injury, neuropathic pain, functional outcome, SCIM, mRFG, retrospective study

Yimin Liang,&ast; Jingyao Liang,&ast; Qiongxiao Huang, Xin Tian, Lei Shao, Manqi Xia, Yumei Liu Institute of Dermatology, Guangzhou Medical University, Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yumei Liu, Department of Dermatology, Guangzhou Institute of Dermatology, 56 HengFu Road, Guangzhou, 510095, People’s Republic of China, Tel +86-13660403350, Email liuyumei1109@163.comAbstract: Knuckle pads (KPs) are benign hyperkeratotic fibrous thickening skin disorder characterized by nodules or plaques located on the extensor surface of the joints. However, there are no specific treatments for KPs so far. Here, we reported a case of KPs successfully treated with 2% crisaborole ointment combined with triamcinolone acetonide and neomycin plaster. This combined therapy might be a new therapeutic option for KPs.Keywords: knuckle pads, crisaborole, PDE-4 inhibitors, primary, emerging therapy

Yuelong Liang,1,&ast; Zhengze Huang,1,&ast; Xuqiu Shen,1,&ast; Yiyin Zhang,1 Yihan Chai,1 Kexin Jiang,1 Qi Chen,2 Feng Zhao3 1Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of General Surgery, Hangzhou Fuyang Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuelong Liang; Feng Zhao, Email yuelongliang@zju.edu.cn; fengzhao3901@zju.edu.cnBackground: Antimicrobial peptides (AMPs) can act on the bacterial cell membrane to play an antibacterial role in types of drug-resistant bacteria. Therefore, AMPs have attracted more and more attention in the treatment of drug-resistant bacteria.Methods: Bibliometric analysis was employed to sort out the development and trends in the research of AMPs in the treatment of drug-resistant bacteria and map the knowledge structure for scholars.Results: Since 2010, the publications and citations in this field have exploded, indicating a growing global interest in the field of AMPs for the treatment of drug-resistant bacteria. And as major countries in this field, China and the USA had conducted very in-depth exchanges and cooperation, which had injected a steady stream of impetus into this field. Both old and new scholars have made efforts, and related fields have developed rapidly, especially in the synthesis and improvement of novel AMPs. In recent years, research directions in the field of AMPs for the treatment of drug-resistant bacteria gradually focused on the practical application, optimization of drug delivery mode, optimization of synthesis mode, screening of new AMPs and other fields, indicating that the relevant research results of AMPs for the treatment of drug-resistant bacteria had entered the actual clinical stage, with higher practical significance.Conclusion: The research history, global research status, future research hotspots, and trends of the research of AMPs in the treatment of drug-resistant bacteria were discussed in depth in this study, which can provide research references and inspiration for researchers inside and outside the related field.Keywords: antimicrobial peptides, AMP, drug-resistant bacteria, bibliometric

Xiangzhen Nan, Jijie Yu, Yafeng Liang, Pengcheng Lou, Guoquan Pan Department of Pediatric Intensive Care Unit, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Guoquan Pan, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Tel +86-13806882183, Email 81801800@163.comObjective: The aim of this study was to explore the value of applying different sampling methods combined with metagenomic next-generation sequencing (mNGS) to detect pathogens in children with severe pneumonia on mechanical ventilation.Methods: Forty children with severe pneumonia on mechanical ventilation were selected, and routine endotracheal suctioning and bronchoalveolar lavage fluid (BALF) sampling methods were performed. The diagnostic efficacy of different sampling methods combined with mNGS versus traditional etiological pathogen detection strategies was compared.Results: The positive rate of mNGS pathogen detection after routine endotracheal suctioning and BALF sampling was higher than that of traditional etiological detection strategies (P < 0.05). There was no significant difference in the positive rates of pathogen detection by routine endotracheal suctioning + mNGS and BALF + mNGS (P > 0.05).Conclusion: Compared with traditional etiological detection strategies, mNGS is more efficient for diagnosing pathogens. In clinical practice, an appropriate sampling method should be selected for mNGS-based detection according to the condition of the patient. These findings could be of great importance in the diagnosis and treatment of severe pneumonia.Keywords: sampling method, next-generation sequencing, severe pneumonia, metagenomics, mechanical ventilation

Fei Jiang,&ast; Ailing Wu, Yan Liang, Hui Huang, Wei Tian, Bogang Chen, Di Liu&ast; Department of Anesthesiology, The First People’s Hospital of Neijiang, Neijiang, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Di Liu, Department of Anesthesiology, The First People’s Hospital of Neijiang, No. 1866 Han’an Dadao West Section, Shizhong District, Neijiang, Sichuan, People’s Republic of China, Tel +86 3541633502, Email liudimzk@126.comPurpose: Adequate postoperative analgesia is a key to earlier recovery from open surgery. This work investigated the pain control and quality of patient recovery after hepatectomy to evaluate the modified continuous serratus anterior plane block (called low SAPB) for postoperative analgesia.Patients and Methods: This single-center, blinded, randomized, controlled study included 136 patients who underwent hepatectomy under general anesthesia. For postoperative analgesia, the patients in the SAPB group were given a continuous low SAPB at the 7th intercostal space in the right mid-axillary line, and the patients in the control group were given continuous intravenous opioid analgesia. The numeric pain rating scale (NPRS) was used for pain assessment. The postoperative assessment focused on the remedial drug consumption, the occurrence of adverse postoperative analgesic reactions, and the quality of patient recovery evaluated with the QoR-15 questionnaire.Results: Compared to the controls, the SAPB patients had significantly lower NPRS scores at 12 h and 24 h at rest and 6 h, 12 h, and 24 h in motion, and a longer time to first use of remedial analgesics at 24 h, and higher overall QoR-15 scores at 24 h [124 (121, 126) vs 121 (120, 124)] and 48 h [129 (126, 147) vs 126 (125, 128)], after surgery. There was no significant difference in the incidence of analgesia-related adverse reactions between the two groups.Conclusion: The continuous low SAPB could achieve superior pain control, especially for motor pain, to intravenous opioid analgesia during the first 24 h post-surgery. Even with no significant difference in the incidence of postoperative adverse reactions, patients with continuous low SAPB appeared to have a higher quality of recovery in the first two days post-surgery than patients with continuous intravenous analgesia.Keywords: liver resection, postoperative analgesia, serratus anterior plane block

Wanyi Chen,1,&ast; Po-Han Fang,2,&ast; Bin Zheng,3 Yue Liang,1 Yiwen Mao,1 Xuefeng Jiang,1 Qionglan Tang4 1Department of Obstetrics and Gynecology, the First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2International School, Jinan University, Guangzhou, People’s Republic of China; 3Guangdong Research Center for Organoid Engineering and Technology, Guangzhou, People’s Republic of China; 4Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qionglan Tang, Email qionglantang@126.comAbstract: So far, ovarian cancer has still been the most lethal gynecological malignancy. The chemotherapy and targeted medication are the mainstay for the recurrent ovarian cancer treatment. About 70% of the advanced-stage cases will relapse. Ascites-derived organoid is a pre-clinical model for the precise prediction of the therapeutic effectiveness for the ovarian cancer: it can be used to assess the drug sensitivity, to guide individualized precise treatment, and to improve advanced stage as well as recurrent ovarian cancer patient’ survival and prognosis. Until now, there has been no report concerning the establishment of the organoid out of the patient’s ascites and the concurrent usage of drug sensitivity test to guide the individualized precise treatment for the ovarian cancer. Here, we report a case of recurrent ovarian cancer of a 59-year-old female patient whose CA125 at its peak increased to 4523.4 U/mL. Then, patient’s own ovarian cancer organoid was constructed from the ascites by the abdominocentesis; concurrently, medication sensitivity test was performed on the organoid to guide individualized precise treatment. After the treatment, CA125 decreased to 33.7 U/mL, and the patient’s condition relieved effectively. This is the first published case report using ascites-derived organoid and the drug sensitivity test thereof to guide the precise treatment of recurrent ovarian cancer.Keywords: ascites-derived organoid, ovarian cancer organoid, recurrent ovarian cancer, drug sensitivity test, precise treatment

Yi Liang,1,2 Xiaohong Li,1 Fang Wang,2 Zongting Yan,2 Yuhuan Sang,2 Yuan Yuan,2 Yun Qin,1 Xuefei Zhang,1 Mei Ju2 1Health Management Center, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Nursing College, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of ChinaCorrespondence: Mei Ju; Xiaohong Li, Email 593576753@qq.com; 1848922774@qq.comBackground: Thyroid nodules (TNs) are among the most common thyroid lesions, and rates of these nodules have risen over the past three decades. As the majority of TN patients remain asymptomatic when these nodules are in the early stages of development, malignant nodules may continue to develop into thyroid cancer when not detected. As such, early screening and diagnosis-based strategies represent the most promising means of preventing or treating TNs and associated cancers. The present study was thus developed to explore TN prevalence among individuals in Luzhou, China.Methods: Here, thyroid ultrasonography and metabolic-related indicators from 45,023 adults undergoing routine physical examinations in the Health Management Center of a large Grade A hospital in Luzhou over the last three years were retrospectively reviewed in an effort to identify factors associated with TN risk and the detection of these nodules through univariate and multivariate logistic regression analyses.Results: In total, 13,437 TNs were detected in these 45,023 healthy adults for an overall 29.8% detection rate. This TN detection rate rose with age, and multivariate logistic regression analyses revealed that independent risk factors associated with TNs included greater age (≥ 31 years old), female (OR = 2.283, 95% CI: 2.177– 2.393), central obesity (OR = 1.115, 95% CI: 1.051– 1.183), impaired fasting glucose (OR = 1.203, 95% CI: 1.063– 1.360), overweight status (OR = 1.085, 95% CI: 1.026– 1.147), and obesity (OR = 1.156, 95% CI: 1.054– 1.268), while low BMI was a protective factor associated with lower rates of TN incidence (OR = 0.789, 95% CI: 0.706– 0.882). When results were stratified by gender, impaired fasting glucose was not an independent predictor of TN risk among males, while high LDL levels were an independent predictor of TNs among females, and other risk factors were not significantly changed.Conclusion: TN detection rates were high among adults in Southwestern China. Female, elderly individuals, individuals exhibiting central obesity, and those with high levels of fasting plasma glucose are more likely to develop TN.Keywords: thyroid nodules, detection rate, influence factors

ZeYu Xu,1,&ast; Ou Li,1,&ast; YaTing Liang,1,&ast; ZhiBing Wu,2 Jiamei Xu,2 Ling Wang,3 Ling Li,3 YongNing Sun1 1Department of Brain and Mental Disease, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, ShangHai, 200040, People’s Republic of China; 2Department of Encephalopathy, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China; 3Department of Geriatrics, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi’an, 710003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: YongNing Sun, Shanghai University of Traditional Chinese Medicine, Shanghai, 200040, People’s Republic of China, Tel +8618930177579, Email ynsun2002@126.comBackground: Alzheimer’s disease (AD) is a common degenerative disease of the nervous system with serious impact on quality of life of patients and their families. With an aging population, AD has become a major public health problem in China and worldwide. However, the physiological and pathological mechanisms of AD have not been fully elucidated, and there is a lack of effective prevention and clinical treatment methods. Many studies have found that traditional Chinese medicine (TCM) has a good therapeutic effect on cognitive function in AD patients. Bu Shen Kai Qiao Fang (BSKQF) is one such Chinese herbal preparation used in the treatment of AD. We designed a protocol for a real-world clinical study of BSKQF combined with Donepezil hydrochloride (DH) to evaluate the efficacy and safety of this approach in the treatment of AD patients.Methods: This is a protocol for a real-world, multicenter, prospective, observational cohort study. The study will recruit 860 AD patients from four hospitals across China. Equal numbers of patients will be treated with BSKQF and DH or with DH only. The criteria for grouping are based primarily on patient preference. Outcome measures include scores on the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MOCA) and will be recorded at baseline, and at one, two and three months after enrollment. The plasma Aβ 42 and plasma Tau levels of participating patients will also be measured by ELISA at baseline and after 3 months of treatment. Safety metrics and adverse events (AEs) of participating patients will be monitored and recorded.Discussion: This study will evaluate the clinical efficacy and safety of BSKQF in the treatment of AD. The results will provide reliable evidence for the clinical application of BSKQF in the treatment of AD.Study Registration: Trial registration: Chinese Clinical Trial Registry, NO. ChiCTR2000039670, Registered 5 November 2020 https://www.chictr.org.cn/showprojEN.html?proj=63800.Keywords: Alzheimer’s disease, Bu Shen Kai Qiao Fang, real-world trial, MMSE, MOCA, Aβ 42, tau

Peng Chen,1 Zhongxin Li,2 Yulong Liang,1 Ming Wei,2 Haibo Jiang,2 Shihao Chen,2 Zengren Zhao2 1Department of General Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2Department of General Surgery, The First Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of ChinaCorrespondence: Zengren Zhao, Department of General Surgery, The First Affiliated Hospital of Hebei Medical University, No. 89 Donggang Road, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email zhaozengren@hebmu.edu.cnPurpose: Colon cancer is the main malignant tumor of the digestive tract. Hypoxia is highly related to the occurrence, progression and tumor immune microenvironment (TIME) of cancer. The aim of this study was to identify a hypoxia-associated signature with high accuracy for predicting the prognosis and TIME of colon cancer.Methods: Download colon cancer data from the GEO and TCGA databases. A novel hypoxia risk model was identified to predict the prognosis of colon cancer patients. Subsequently, GSEA, TIME and mutation analysis were performed in the hypoxia high and low risk score groups. Finally, the signature gene ANKZF1 was selected for functional verification at the cellular level.Results: A novel hypoxia risk model was identified. The risk score was significantly associated with poorer overall survival in colon cancer, and could be used as an independent prognostic factor for colon cancer. GSEA analysis found that the processes related to stimulate tumor proliferation and anti-apoptosis were significantly enriched in the hypoxia high risk score group. The expression of immunosuppressive cells and most immune checkpoints in the high risk score group was significantly higher than that in the low risk score group. In vitro cell experiments showed that knockdown the expression of ANKZF1 could inhibit the proliferation, migration and invasion of colon cancer cells.Conclusion: Hypoxia plays an important role in evaluating the TIME and predicting the prognosis of colon cancer.Keywords: colon cancer, hypoxia, prognosis, risk score, tumor immune microenvironment

Jingwen Zhang,1,&ast; Liying Liu,1,&ast; Manjia Zhu,2 Xiaoyan Zheng,1,3 Yun Liang,1 Ying Zhong,3 Jing Xu,1 Jie Yang1,3 1Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 2Basic Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 3Sichuan Jinxin Xi’nan Women’s and Children’s Hospital, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Yang; Jing Xu, Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China, Tel +86 13882296714, Email jenny_yang_jie@126.com; 195940644@qq.comBackground: Over the past decade, acupuncture in the perioperative period has attracted great interest, and a growing number of related literature has been published.Purpose: To analyze the general information and identify the research hotspots and trends of acupuncture in perioperative medicine in the last 10 years by bibliometric analysis.Methods: We searched the Web of Science Core Collection for publications on acupuncture in perioperative medicine from 2013 to 2023. The articles and reviews were collected with no language restriction. CiteSpace and VOSviewer software were used for bibliometric and visual analysis of relevant literature.Results: A total of 814 bibliographic records were retrieved. Overall, the annual number of publications showed an increasing trend. China and its institutions were in a leading position regarding the publication number. With comparatively more scientific collaboration with China, the USA ranked second. Shanghai University of Traditional Chinese Medicine was the most prolific institution. Ha, In-Hyuk had the most publications, and Han JS and Lee A were the most cited authors. Medicine was the most popular journal and Journal of Clinical Oncology had the highest impact factor. “Acupuncture”, “electroacupuncture” and “postoperative pain” were the top three keywords. The most popular topics were postoperative pain, postoperative ileus, and postoperative nausea and vomiting according to the keywords and references. And the clusters of postoperative cognitive dysfunction, anxiety, and breast cancer attracted relatively more attention recently.Conclusion: This study summarized the research status, hotspots, and trends of acupuncture in perioperative medicine in the past decade, which may aid researchers in better understanding this field. The research hotspots primarily focused on postoperative pain management and postoperative gastrointestinal function. The research of acupuncture for postoperative cognitive dysfunction, cancer-related surgery, and psychological states were the main frontiers topics and may be the focus in the future.Keywords: acupuncture, perioperative medicine, post-operative, mid-operative, CiteSpace, VOSviewer

Lin Jin,1 Yafen Liang,2 Ying Yu,1 Peng Miao,1 Yihao Huang,1 Liying Xu,1 Huilin Wang,1 Chunsheng Wang,3 Jiapeng Huang,4 Kefang Guo1 1Department of Anesthesia, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Anesthesiology, University of Texas Health Center at Houston, Houston, TX, USA; 3Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 4Department of Anesthesiology & Perioperative Medicine University of Louisville, Louisville, KY, USACorrespondence: Kefang Guo, Department of Anesthesia, Zhongshan Hospital, Fudan University, No. 180, Fenglin Road, Xuhui District, Shanghai, People’s Republic of China, Email dr_guokefang@163.com Jiapeng Huang, Department of Anesthesiology & Perioperative Medicine University of Louisville, Louisville, KY, 40202, USA, Email jiapeng.huang@louisville.eduObjective: To investigate the feasibility of multimodal regimen by paracetamol, gabapentin, ketamine, lidocaine, dexmedetomidine and sufentanil among cardiac surgery patients, and compare the analgesia efficacy with conventional sufentanil-based regimen.Design: A single-center, prospective, randomized, controlled clinical trial.Setting: One participating center, the cardiovascular center of the major integrated teaching hospital.Participants: A total of 115 patients were assessed for eligibility: 108 patients were randomized, 7 cases were excluded.Interventions: The control group (group T) received conventional anesthesia management. Interventions in the multimodal group (group M) were as follows in addition to the standard of care: gabapentin and acetaminophen 1 hour before surgery; ketamine for induction and to maintain anesthesia with lidocaine and dexmedetomide. Ketamine, lidocaine, and dexmedetomidine were added to routine sedatives postoperatively in group M.Measurements and Main Results: The incidence of moderate-to-severe pain on coughing made no significant difference (68.5% vs 64.8%, P=0.683). Group M had significantly less sufentanil use (135.72μg vs 94.85μg, P=0.000) and lower rescue analgesia rate (31.5% vs 57.4%, P=0.007). There was no significant difference in the incidence of chronic pain, PONV, dizziness, inflammation index, mechanical ventilation time, length of stay, and complications between the two groups.Conclusion: Our multimodal regimen in cardiac surgery is feasible, but was not superior to traditional sufentanil-based regimen in the aspects of analgesia effects; however, it did reduce perioperative opioid consumption along with rescue analgesia rate. Moreover, it showed the same length of stay and the incidences of postoperative complications.Keywords: cardiac surgery, multimodal analgesia, prognosis

Yihuai Liang,1,2 Wenrou Su,1,2 Feifei Wang1– 3 1Research and Development Center, Yunnan Botanee Bio-Technology Group Co. Ltd, Shanghai, People’s Republic of China; 2Yunnan Yunke Characteristic Plant Extraction Laboratory Co. Ltd, Kunming, Yunnan, People’s Republic of China; 3Medaesthee (Shanghai) Biotechnology Co., Ltd, Shanghai, People’s Republic of ChinaCorrespondence: Feifei Wang, Research and Development Center, Yunnan Botanee Bio-Technology Group Co. Ltd, No. 999 Huaxu Road, Shanghai, 201702, People’s Republic of China, Tel +86 21 39880807, Email wangfeifei@winona.cnAbstract: Of the human organs, skin is the most visible one that displays the manifestations of ageing. It has a very intricate microanatomical structure and performs several key physiological functions. The pathophysiology of cutaneous ageing is characterized by deterioration of structural stability and functional integrity, implying a continuous reduction in maximal function and reserve capacity, as a result of the accumulating damage due to both intrinsic and extrinsic factors. Elimination of unfavorable expressions associated with facial and cutaneous ageing is the key patient demand in aesthetic dermatology. Even though the progress has been made in nonsurgical therapies like fillers and lasers, non-invasive interventions by using skin care products designed for rejuvenation at an early stage are the most popular and accessible solution among people. In this review, we have scrutinized the ageing-associated cutaneous changes at molecular, cellular and tissue levels. To optimize the ageing process towards a healthy skin, we propose an integrated, multilayer-targeted intervention, which involves both topical application of anti-ageing formulations from outside and oral supplementation from inside. Additionally, several promising naturally derived ingredients are reviewed from an anti-aging perspective. Most of them possess various bioactivities and may contribute to the development of the mentioned anti-ageing remedy.Keywords: skin barrier, skin ageing, causative factors, anti-ageing remedy, naturally derived ingredients

Peigen Wu,1– 3 Churui Chang,3 Guanglin Zhu,4 Lixiang Zhai,5 Xu Zhang,3 Qiuchan Huan,1,3 Zhengxian Gao,1,3 Huan Deng,2 Yue Liang,1 Haitao Xiao2,3 1Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 2School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, People’s Republic of China; 3School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guizhou, People’s Republic of China; 4Traditional Chinese Medicine Hospital of Qijiang, Chongqing, People’s Republic of China; 5School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong Special Administrative Region, People’s Republic of ChinaCorrespondence: Haitao Xiao, School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, 518060, People’s Republic of China, Email xhaitao@szu.edu.cn Yue Liang, Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China, Email bmqueen@163.comPurpose: To explore the potential mechanism of glycosidic fraction of Picrorhiza scrophulariiflora Pennell (GPS) extract for the treatment of colitis using UPLC-QTOF-MS analysis, network pharmacology and experimental research.Methods: The active components of GPS extract were identified by UPLC-QTOF-MS analysis and extracted their targets from the databases, which was used for network pharmacology analysis. Kyoto Encyclopedia of genes and genomes (KEGG) pathway analysis was performed to discover potential therapeutic mechanisms, and the network pharmacology results were then validated by in vivo and in vitro experiments.Results: The results showed that GPS extract significantly alleviated the clinical signs of colitis, including body weight, disease activity index, colon shortening, and colon tissue damage, and inhibited the transcription and production of colonic IL-1β and IL-6 in DSS-induced colitis mice. In vitro, GPS extract also significantly suppressed nitric oxide (NO) production, iNOS expression, IL-1β and IL-6 transcription of LPS-activated RAW 264.7 cells. Network pharmacology integrated with experimental validation identified that GPS extract significantly suppressed Akt, p38, ERK, and JNK phosphorylation in vivo and in vitro, and luteolin, apocynin, caffeic acid, caffeic acid methyl ester, luteoloside, picroside II, aucubin, cinnamic acid, vanillic acid, and sweroside were the main components responsible for the anti-inflammatory effect of GPS. These findings demonstrate that the potential anti-inflammatory effect of GPS extract against colitis is achieved through suppressing PI3K/Akt and MAPK pathways, and that the abovementioned active components mainly exerted its anti-inflammatory effect.Conclusion: The therapeutic effect of GPS extract on colitis is related to PI3K/Akt and MAPK pathways, which is a promising remedy for colitis therapy.Graphical Abstract: Keywords: Picrorhiza scrophulariiflora, colitis, bioactive compounds, molecular mechanism, network pharmacology

Xichun Xia,1,2,&ast; Hai Yu,3,&ast; Yanxiang Li,2 Yunting Liang,1 Guangqiang Li,2 Fang Huang1 1Department of Dermatology, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai, 519050, People’s Republic of China; 2The Biomedical Translational Research Institute, Health Science Center (School of Medicine), Jinan University, Guangzhou, 510632, People’s Republic of China; 3Department of Dermatology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangqiang Li, No. 601, West Huangpu Road, Tianhe, Guangzhou, Guangdong, 510632, People’s Republic of China, Tel +86 15521006500, Fax +8620-85226420, Email guangq.lee@gmail.com Fang Huang, No. 79, Kangning Road, Xiangzhou District, Zhuhai, Guangdong, 519050, People’s Republic of China, Tel +86 13923373864, Fax +8620-85226420, Email huangfang67@sohu.comPurpose: Psoriasis is a systemic inflammatory disease, and the mechanism that links psoriasis to depression is still elusive. Hence, this study aimed to elucidate the potential pathogenesis of psoriasis and depression comorbidity.Methods: The gene expression profiles of psoriasis (GSE34248, GSE78097 and GSE161683) and depression (GSE39653) were downloaded from the Gene Expression Omnibus (GEO) DataSets. Functional annotation, protein‐protein interaction (PPI) network and module construction, and hub gene identification and co-expression analysis were performed, following identification of the common differentially expressed genes (DEGs) of psoriasis and depression.Results: A total of 115 common DEGs (55 up-regulated and 60 down-regulated) were identified between psoriasis and depression. Functional analysis indicated that T cell activation and differentiation were predominantly implicated in the potential pathogenesis of these two diseases. In addition, Th17 cell differentiation and cytokines is closely related to both. Finally, 17 hub genes were screened, including CTLA4, LCK, ITK, IL7R, CD3D, SOCS1, IL4R, PRKCQ, SOCS3, IL23A, PDGFB, PAG1, TGFA, FGFR1, RELN, ITGB5 and TNXB, which re-emphasized the importance of the immune system in psoriasis and depression.Conclusion: Our study reveals the common pathogenesis of psoriasis and depression. These common pathways and hub genes may apply to a molecular screening tool for depression in psoriasis patients, which could help dermatologists optimize patient management in routine care.Keywords: psoriasis, depression, bioinformatics, differentially expressed genes, hub genes

Zhihan Jiang,1,&ast; Xiaosen Wang,1,&ast; Lijiao Zhang,1,&ast; Drolma Yangzom,2,&ast; Yanping Ning,2 Baiyan Su,3,4 Meijiao Li,5 Meilang ChuTso,2 Yahong Chen,1,6 Ying Liang,1,2,6 Yongchang Sun1,6 1Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Tibet Autonomous Region People’s Hospital, Lhasa, 850000, People’s Republic of China; 3Radiology Department, Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 4Radiology Department, Tibet Autonomous Region People’s Hospital, Lhasa, 850000, People’s Republic of China; 5Radiology Department, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 6Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, 100083, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Liang; Yongchang Sun, Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, North Garden Road 49, Haidian District, Beijing, People’s Republic of China, Tel +86 138 1096 4766 ; +86 139 1097 9132, Email bysyliangying@126.com; suny@bjmu.edu.cnBackground: COPD patients living in Tibet are exposed to specific environments and different risk factors and probably have different characteristics of COPD from those living in flatlands. We aimed to describe the distinction between stable COPD patients permanently residing at the Tibet plateau and those in flatlands.Methods: We conducted an observational cross-sectional study that enrolled stable COPD patients from Tibet Autonomous Region People’s Hospital (Plateau Group) and Peking University Third Hospital (Flatland Group), respectively. Their demographic information, clinical features, spirometry test, blood routine and high-resolution chest CT were collected and evaluated.Results: A total of 182 stable COPD patients (82 from plateau and 100 from flatland) were consecutively enrolled. Compared to those in flatlands, patients in plateau had a higher proportion of females, more biomass fuel use and less tobacco exposure. CAT score and frequency of exacerbation in the past year were higher in plateau patients. The blood eosinophil count was lower in plateau patients, with fewer patients having an eosinophil count ≥ 300/μL. On CT examination, the proportions of previous pulmonary tuberculosis and bronchiectasis were higher in plateau patients, but emphysema was less common and milder. The ratio of diameters of pulmonary artery to aorta ≥ 1 was more often in plateau patients.Conclusion: Patients with COPD living at Tibet Plateau had a heavier respiratory burden, lower blood eosinophil count, less emphysema but more bronchiectasis and pulmonary hypertension. Biomass exposure and previous tuberculosis were more common in these patients.Keywords: chronic obstructive pulmonary disease, plateau, phenotype, computed tomography, emphysema

Hainan Wen,1 Shoujun Xie,1 Yanchao Liu,1 Yueyi Liang,1 Pan Zhang,1 Xiaohui Wang,1 Jianhui Li2 1Department of Clinical Laboratory, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, People’s Republic of China; 2Department of Preventive Medicine, Chengde Medical University, Chengde, Hebei, People’s Republic of ChinaCorrespondence: Jianhui Li, Email wow99wow@126.comObjective: Enterobacteriaceae have displayed widespread trends of antimicrobial resistance in recent years. Therefore, we aimed to analyse the antimicrobial susceptibility of common bacteria and explore the significance in treatment and research of infections induced by Enterobacteriaceae.Methods: We retrospectively analysed 10,775 antimicrobial susceptibility test results acquired over a 6-year period in the affiliated hospital of Chengde Medical University. We divided the data based on specimen type (blood, sputum, pus, or urine), and population characteristics (age bracket and sex) for analysis. We mainly analysed the antimicrobial susceptibility of Escherichia coli (Eco), Klebsiella pneumoniae (Kpn), and Enterobacter cloacae (Ecl).Results: In our study, it was found that the resistance rates of Eco, Kpn, and Ecl to most antimicrobial agents were significantly different (P < 0.05) on specimen type and age bracket. The Eco from sputum had the highest resistance rates except ciprofloxacin (CIP), levofloxacin (LVX), and gentamicin (GEN); the Kpn from urine had the highest resistance rates to all antimicrobial agents; the Ecl from urine had the highest resistance rates to most antimicrobial agents. The Eco from geriatric patients had the highest resistance rates except GEN and SXT; the Kpn from adult patients had the lowest resistance rates to most antimicrobial agents except LVX. The Eco isolated from males had higher resistance rates to most antimicrobial agents except CIP, LVX, and NIT than those isolated from females; the Kpn showed significant differences in antimicrobial susceptibility to only 5 out of 22 antimicrobial agents (P < 0.05); the Ecl showed significant differences in susceptibility only to two antimicrobial agents, LVX and TOB (P < 0.01).Conclusion: The antimicrobial susceptibility of Enterobacteriaceae was significantly different among specimen type, age bracket and sex of patients, which is of great significance for the treatment and research of infection.Keywords: Enterobacteriaceae, antimicrobial sensitivity, drug resistance, specimen type, infection

Jianhong Li,1 Yingna Liang2 1Department of Radiology, Foshan Hospital of Traditional Chinese Medicine, Foshan, People’s Republic of China; 2Department of Gynaecology and Obstetrics, Guangzhou Baiyun First People’s Hospital (Baiyun District Maternal and Child Health Hospital), Guangzhou, Guangdong Province, People’s Republic of ChinaCorrespondence: Yingna Liang, Department of Gynaecology and Obstetrics, Guangzhou Baiyun First People’s Hospital (Baiyun District Maternal and Child Health Hospital), Guangzhou, Guangdong Province, People’s Republic of China, Email liangyn123@126.comObjective: In this study, it was intended to explore the causal association between mean platelet volume (MPV) and risk of deep vein thrombosis (DVT) using a two-sample Mendelian randomization (MR) analysis and a retrospective study.Methods: This study applied two-sample MR analysis to estimate the causal association between MPV and risk of DVT. Twenty-one single nucleotide polymorphisms (SNPs) were selected as genetic variants from two independent consortiums cohorts (p-value < 5× 10− 8, linkage disequilibrium r2< 0.1). Inverse variance weighted (IVW), MR-egger method and weighted median were performed. A retrospective study was also conducted to verify the associations identified from the MR study.Results: The MR analysis demonstrated that genetically predicted higher MPV was associated with significantly lower risk of DVT (OR 0.982, 95% CI = 0.967– 0.998, P = 0.023), with the consistent result in weighted median and MR-Egger. There was no directional horizontal pleiotropy in the method of MR-Egger regression (intercept=2.9e-04, P = 0.194). There was no single SNP was found to strongly drive the combined causal effect in the leave-one-out sensitivity analysis. Additionally, the similar result was observed in the retrospective study.Conclusion: This study suggested that MPV was negatively associated with the risk of DVT. More basic researches are needed in the future to explore its specific mechanism.Keywords: mean platelet volume, deep vein thrombosis, Mendelian randomization, causal association

Peng Liang, Yingjie Sun, Yue Li, Yundan Liang Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu, People’s Republic of ChinaCorrespondence: Yundan Liang, Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan, 610500, People’s Republic of China, Tel/Fax +86-28-62739308, Email liangyundan2004@126.comBackground: Depression is among the most common psychiatric disorders, and is a leading cause of the global disease burden. Its pathophysiological mechanism is unclear, which limits the development of therapeutic strategies. Long non-coding RNA (lncRNA) single nucleotide polymorphisms (SNPS) may be related. In this study, we aimed to determine the effects of the rs2242385, rs155979, rs3762983, and rs3762984 polymorphisms in the lncRNA NONHSAT102891 on depression susceptibility in a Chinese population.Methods: We conducted a case-control study in a cohort of 480 patients with depression and 329 healthy controls, and performed genotyping by gene sequencing ii.Results: The rs155979 GC genotype was significantly associated with increased risk of depression compared with healthy controls. Stratified analysis showed a 2.08-fold increased risk of suicide in patients with rs155979 GC or GG genotype. The rs2242385, rs3762983, and rs3762984 polymorphisms were not significantly associated with the risk of depression. Haploid analysis showed linkage disequilibrium between rs155979, rs3762983, and rs3762984, and the CCG haplotype reduced the risk of depression.Limitations: The study sample was relatively small, and was restricted to patients from central and southern China. Further, only peripheral blood was used for DNA extraction.Conclusion: The rs155979 polymorphism may be associated with the occurrence of depression in the Chinese population. However, further studies are needed to verify the reliability of our results in large populations and different ethnic groups.Keywords: depression, SNP, LncRNA

Weitong Li,1,&ast; Haiyan Yin,1,&ast; Yulei Song,1 Wenjing Tu,1 Lulu Wang,1 Yongqi Liang,1 Yamei Bai,1,&ast; Guihua Xu2,&ast; 1School of Nursing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guihua Xu, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China, Email 7115@njucm.edu.cnBackground: Social isolation is a serious and pervasive health issue among older people, and it is difficult to identify and assess effectively. Based on a thorough and scientific evaluation index system, AHP-Fuzzy comprehensive evaluation could be a valuable technique.Objective: It is crucial to establish interventions that focus on risk factors for the prevention of social isolation in order to give a strong scientific foundation for enhancing older people’s health habits. This can be achieved by using a fuzzy comprehensive evaluation method to assess the risk of social isolation in older people.Methods: A hundred community members over 60 from Nanjing were selected as the evaluation subjects in China. After the element layer was split into three categories of “social risk, economic risk, and cultural risk” using the analytic hierarchy process approach, a total of 22 assessment indicators were picked to develop a risk evaluation index system.Results: The risk level of social isolation belonging to the “low risk, relatively low risk, medium risk, relatively high risk, high risk” of membership degree are respectively “ 0.3392, 0.2632, 0.2257, 0.1069, 0.0650”. Fuzzy comprehensive evaluation analysis showed that social relations (0.4934), monthly income (0.4654), health status (0.5960) were significant factors of social isolation risk in older people. The results showed that factors related to social risk had the most significant impact on social isolation.Conclusion: It is scientific and feasible to construct the risk evaluation index model of social isolation risk for the elderly by using AHP-Fuzzy comprehensive evaluation method. In preventing social isolation of older people in the future, we should pay attention to the impact of social and cultural factors on them, and provide practical intervention programs and references from the government, community, family.Keywords: AHP, fuzzy comprehensive evaluation method, social isolation, older people

Yuqi Liang,1,2,&ast; Guosong Wu,3,&ast; Tianyu Luo,1,2,&ast; Haimei Xie,2 Qian Zuo,2 Ping Huang,2 Huachao Li,2 Liushan Chen,2 Hai Lu,4,&ast; Qianjun Chen1,2,&ast; 1The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, People’s Republic of China; 2Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 3Nanfang Hospital Baiyun Branch, Guangzhou, Guangdong, 510000, People’s Republic of China; 4The First People’s Hospital of Shaoguan, Shaoguan, Guangdong, 512099, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qianjun Chen, Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Yuexiu District, Guangzhou, 510102, People’s Republic of China, Email cqj55@163.com Hai Lu, The First People’s Hospital of Shaoguan, No. 3, South Dongdi Road, Shaoguan, 512099, People’s Republic of China, Tel +86 15622187291, Email hysa1985@163.comPurpose: Although paclitaxel is widely used in cancer treatment, severe side effects and drug resistance limit its clinical use. 10-gingerol (10-G) is a natural compound isolated from ginger, which displays anti-inflammatory, antioxidant, and antiproliferative properties. However, the chemotherapy-sensitization effect of 10-G on triple-negative breast cancer (TNBC) has not been fully clarified. This study is aimed at investigating the effect of 10-G on the paclitaxel sensitivity in TNBC, and its underlying mechanism.Methods: The study was determined through in vitro and in vivo experiments. Cell viability and proliferation were detected by cell counting kit 8 (CCK-8) and colony formation. To detect cell apoptosis, flow cytometry and TUNEL were used. The expression of proteins was detected by Western blotting and immunohistochemistry. The molecular docking and gene knockout were corroborated by interactions between 10-G and adrenoceptor Beta 2 (ADRB2). The body weight of mice, histopathology and organs (kidney and spleen) coefficients were used to monitor the drug toxicities.Results: In vitro, 10-G increased the sensitivity of TNBC cells to paclitaxel, and could synergistically promote the apoptosis of TNBC cells induced by paclitaxel. In combination with molecular docking and lentivirus knockdown studies, ADRB2 was identified as a 10-G binding protein. 10-G inhibited ADRB2 by binding to the active site of ADRB2. Knockdown of ADRB2 reduces the proliferation activity of TNBC cells but also attenuates the sensitizing effects of 10-G to paclitaxel. Western blotting and immunohistochemistry showed that 10-G played an anti-proliferation and chemotherapy-sensitizing role by inhibiting the ADRB2/ERK signal. Toxicity evaluation showed that 10-G would not increase hepatorenal toxicity with paclitaxel.Conclusion: This data suggests that 10-G may be used as a new chemotherapeutic synergist in combination with paclitaxel to enhance anticancer activity. The potential value of ADRB2 as a target for improving chemotherapy sensitivity was also emphasized.Keywords: triple-negative breast cancer, combined therapies, 10-gingerol, paclitaxel, adrenoceptor Beta 2