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Min Zhao,1 Changyi Yang,1 Linhong Zhu,1 Xiaoqian Guo,1 Haiyan Ma,2 Yuanhao Luo,3 Qi Wang,4 Juanjuan Chen4 1Department of Periodontology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 2School of Stomatology, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 3The Second Clinical Medical School, Lanzhou University, Lanzhou, Gansu, 730030, People’s Republic of China; 4Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, People’s Republic of ChinaCorrespondence: Juanjuan Chen; Qi Wang, Email ery_juanjuanchen@lzu.edu.cn; ery_wangqery@lzu.edu.cnIntroduction: Our study investigated the disparities and correlations between oral microbiota and metabolites in pregnant patients with and without periodontitis.Methods: Subgingival plaque samples from all subjects were collected for shotgun metagenomic sequencing and broad-target metabolomics analysis.Results: Forty pathogens, including Porphyromonas gingivalis, Fusobacterium nucleatum, Eubacterium saphenum, Gemella morbillorum, Tannerella forsythia, Streptococcus anginosus group, Selenomonas sputigena etc, were significantly enriched in pregnant patients with periodontitis (PPP). Conversely, symbiotic species such as Morococcus cerebrosus, Streptococcus vestibularis, S. salivarius, S. mitis, and S. pneumoniae were significantly more abundant in healthy controls (HCs). A total of 87 predicted functional modules (PFMs) exhibited significant differences between the two groups; eight PFMs showed high enrichment in PPP with involvement of PPP-enriched species within these pathways. The remaining 79 PFMs encompassing ribonucleotide biosynthesis, carbohydrate, and amino acid metabolism were highly abundant in HCs. For oral microbial metabolome, a total of 105 metabolites related to 150 KEGG pathways displayed significant differences between the two groups. Pathways such as pyruvate metabolism, folate biosynthesis, vascular smooth muscle contraction, and AMPK/mTOR signaling pathway along with their associated metabolites were found to be enriched in PPP, while carbohydrate metabolism predominated among HCs. Spearman’s rank correlation analysis revealed significant positive associations between species enriched in PPP and metabolites enriched in PPP, but significant negative associations between species enriched in PPP and metabolites enriched in HCs.Discussion: Our findings provide potential biomarkers for distinguishing periodontitis during pregnancy while offering valuable insights into mechanisms exploration and clinical intervention.Keywords: Pregnancy-induced periodontitis, oral microbiota composition, predicted functional modules, microbial metabolites profiling, biomarkers identification

Huixin Cheng,1 Xuehan Wang,1 Juyi Yao,2 Chunbo Yang,3 Jian Liu1,4 1The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China; 2Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China; 3Department of Critical Medicine Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 4Department of Intensive Care Unit, Gansu Provincial Maternity and Child Health Hospital/Gansu Provincial General Hospital, Lan Zhou, Gansu Province, People’s Republic of ChinaCorrespondence: Jian Liu, The First Clinical Medical College of Lanzhou University, No. 222 Tianshui South Road, Lanzhou, Gansu Province, 730013, People’s Republic of China, Email medecinliujian@163.comAbstract: Sepsis is a common critical illness characterized by high mortality rates and a significant disease burden. In the context of sepsis-induced organ dysfunction, the lungs are among the initial organs affected, which may progress to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Recent studies have highlighted the crucial roles of mitophagy and ferroptosis in the development and progression of sepsis-induced ALI/ARDS. Identifying key convergence points in these processes may provide valuable insights for the treatment of this condition. In recent years, certain herbs and their bioactive compounds have demonstrated unique benefits in managing sepsis-induced ALI/ARDS by modulating mitophagy or ferroptosis. This review summary the mechanisms of mitophagy and ferroptosis, explores their interactions, and emphasizes their regulatory roles in the progression of sepsis-induced ALI/ARDS. Additionally, it offers a novel perspective on treatment strategies by summarizing various herbs and their bioactive compounds relevant to this condition.Keywords: sepsis, acute lung injury, acute respiratory distress syndrome, mitophagy, ferroptosis

Hui Sun,1,* Haiying Liu,2,* Jinxia Li,1 Jinxin Kou,3 Can Yang1 1Clinical Laboratory, Xi’an International Medical Center Hospital, Xi’an, People’s Republic of China; 2Occupational Health Department, Xi’an Changan District Center for Disease Control and Prevention, Xi’an, People’s Republic of China; 3School of Medicine, Xi’an Siyuan University, Xi’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Can Yang, Email 2798246103@qq.comBackground: This study aims to observe the relationship between novel inflammatory markers and AMI, and analyze its correlation with the degree of coronary artery disease.Methods: Clinical data were collected from the control (510 cases) and AMI (406 cases) groups. The AMI group was classified into mild, moderate and severe according to the Gensini score. Correlation of SII, SIRI, MHR and NHR with Gensini score in AMI patients was analysed using Spearman rank correlation analysis. Factors influencing the degree of coronary lesion in AMI were analysed by multi-factor ordinal logistic regression. The predictive value of the novel inflammatory markers for AMI and its coronary severity was assessed using ROC curves. Risk prediction of the extent of coronary artery disease in AMI using the Nomogram for novel inflammatory indices.Results: The levels of SII, SIRI, MHR and NHR were significantly higher in the AMI group than in the control group. With increasing Gensini score, all four novel inflammatory indices showed an increasing trend. And four novel inflammatory indices were positively correlated with Gensini scores. Meanwhile, SII, SIRI and MHR were independent risk factors for the extent of coronary artery disease in AMI. SII, SIRI, MHR and NHR have good predictive value for AMI, and have predictive value for mild and severe AMI, but have no predictive value for moderate AMI. The nomogram results showed that SII, SIRI and MHR had some predictive value for the degree of coronary artery disease in AMI. The nomogram results showed that SII, SIRI and MHR had some predictive value for the degree of coronary artery disease in AMI.Conclusion: The elevated levels of SIRI, SII, MHR, NHR in AMI patients are independent risk factors for the severity of coronary artery disease in AMI patients, and have predictive value to a certain extent.Keywords: acute myocardial infarction, systemic inflammatory immune index, systemic inflammatory response index, monocyte-to-high-density lipoprotein ratio, neutrophil-to-high-density lipoprotein ratio, clinical predictive value

Zhangxue Wang,1,2,* Chunjuan Yang,3,* Shushan Yan,4,* Jiamei Sun,3,* Jin Zhang,1,2 Zhuojian Qu,5 Wenchang Sun,3 Jie Zang,3 Donghua Xu1– 3 1School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China; 2Department of Rheumatology and Immunology, Weifang People’s Hospital, Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China; 3Central Laboratory, Weifang People’s Hospital, Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China; 4Department of Gastrointestinal and Anal Diseases Surgery, Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China; 5School of Basic Medicine Sciences, Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Donghua Xu; Jie Zang, Email xudh@sdsmu.edu.cn; 18299094039@163.comAbstract: Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from mesoderm. Through cell-to-cell contact or paracrine effects, they carry out biological tasks like immunomodulatory, anti-inflammatory, regeneration, and repair. Extracellular vesicles (EVs) are the primary mechanism for the paracrine regulation of MSCs. They deliver proteins, nucleic acids, lipids, and other active compounds to various tissues and organs, thus facilitating intercellular communication. Rheumatic diseases may be treated using MSCs and MSC-derived EVs (MSC-EVs) due to their immunomodulatory capabilities, according to mounting data. Since MSC-EVs have low immunogenicity, high stability, and similar biological effects as to MSCs themselves, they are advantageous over cell therapy for potential therapeutic applications in rheumatoid arthritis, systemic erythematosus lupus, systemic sclerosis, Sjogren’s syndrome, and other rheumatoid diseases. This review integrates recent advances in the characteristics, functions, and potential molecular mechanisms of MSC-EVs in rheumatic diseases and provides a new understanding of the pathogenesis of rheumatic diseases and MSC-EV-based treatment strategies.Keywords: mesenchymal stem cells, extracellular vesicles, exosome, immunomodulation, rheumatic disease

Guolin Zhao,1,2 Zhijun Wang,1,2 Jun Zhang,1,2 Yuan Lin,1,2 Tang Zhou,1,2 Kaili Liu,1,2 Changyong Yang,1 Cheng Liao1 1Department of Preclinical Research and Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, Jiangsu, People’s Republic of China; 2Department of Preclinical Research and Development, Shanghai Shengdi Pharmaceutical Co., Ltd., Shanghai, People’s Republic of ChinaCorrespondence: Changyong Yang; Cheng Liao, Department of Preclinical Research and Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, Jiangsu, 222000, People’s Republic of China, Tel/Fax +86 021-61629291 ; +86 021-61063826, Email changyong.yang@hengrui.com; cheng.liao@hengrui.comBackground: Interleukin (IL)-4 and IL-13 are critical pathogenic factors for type 2 inflammation-related allergic diseases, sharing the mutual receptor subunit IL-4Rα. However, it was ineffective for certain type 2 inflammation diseases by targeting IL-4, IL-13 ligand alone or both in clinical studies. The work presented herein aimed to evaluate the preclinical efficacy and pharmacokinetics profile of a novel monoclonal antibody against IL-4Rα, SHR-1819, as a promising therapy for type 2 inflammation diseases.Methods: SHR-1819 was generated through immunization by C57BL/6 mice with recombinant hIL-4Rα protein, followed by humanization and affinity maturation. Then, its binding properties with IL-4Rα were determined using surface plasmon resonance (SPR) and ELISA. In vitro inhibitory effects of SHR-1819 were assessed on hIL-4-/hIL-13-induced cell proliferation and signal transducer and activator of transcription 6 (STAT6) signaling activation. In vivo efficacy of SHR-1819 was evaluated in several type 2 inflammatory diseases models, including asthma, atopic dermatitis (AD), and allergic rhinitis (AR) by using hIL-4/hIL-4Rα transgenic mice. Furthermore, the pharmacokinetic (PK) profiles of SHR-1819 were characterized.Results: SHR-1819 showed high binding affinity to human IL-4Rα and effectively blocked IL-4Rα at sub-nanomolar concentration. In vitro assays indicated that SHR-1819 significantly inhibited TF-1 cell proliferation and STAT6 activation induced by hIL-4/hIL-13. In the asthma model, SHR-1819 could reduce airway hyperresponsiveness, decrease serum IgE levels, and alleviated inflammatory lung cell infiltration. In the AD model, SHR-1819 could significantly alleviate inflammatory and skin symptoms. In the AR model, it could remarkably decrease the frequencies of nasal rubbing and sneezing, and inflammatory cell infiltration in nasal tissues. These in vivo efficacy studies demonstrated the therapeutic potential of SHR-1819 in preclinical disease models. Moreover, subcutaneous administration of SHR-1819 exhibited favorable bioavailability in mice.Conclusion: The results supported SHR-1819 as a promising preclinical candidate for the treatment of type 2 inflammatory diseases, including asthma, AD and AR.Keywords: type 2 inflammatory diseases, IL-4Rα, IL-4, IL-13

Chao Yang,1 Haitao Xiao,1 Qizhi Yang,1 Zhendong Zhao,1 Yifan Liu1,2 1Department of Urology, 302 Hospital of China Guizhou Aviation Industry Group, Anshun City, Guizhou Province, 561400, People’s Republic of China; 2Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou City, Guangdong Province, 510000, People’s Republic of ChinaCorrespondence: Yifan Liu, Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou City, Guangdong Province, 510000, People’s Republic of China, Email doctorhorse2008@foxmail.comObjective: This study aimed to assess the association between preoperative neutrophil–lymphocyte ratio (NLR) and febrile urinary tract infection (fUTI) in patients who underwent percutaneous nephrolithotomy (PCNL).Patients and Methods: The clinical data of patients who underwent PCNL at our hospital between March 2020 and May 2023 were retrospectively analyzed. According to whether fUTI occurs after operation, collected data were divided to the patients into fUTI and non-fUTI. Univariate analysis, relative operating characteristic (ROC) curves and multivariate logistic regression analysis were performed on the data.Results: A total of 405 patients were enrolled in the study. The procedure was successfully performed in all patients, and the incidence of fUTI was 8.4% (34/405). Eight patients eventually developed sepsis, and the incidence of sepsis in fUTI patients was 23.5%. The result shows a significant correlation between NLR and fUTI (95% confidence interval [CI],1.21– 1.83, Odds ratio [OR]=1.49, p< 0.001). The predictive ability of NLR on the occurrence of fUTI was assessed by plotting relative operating characteristic (ROC) curves. The area under the curve (AUC) in the ROC curve for NLR was 0.718 according to the Youden index, and the best cut-off value of NLR was 2.71. Furthermore, logistic multiple regression model adjustment was carried out to further confirm the robustness of the relationship between NLR and fUTI. The results indicated robustness regardless of whether NLR was a continuous variable or a categorical variable.Conclusion: NLR can be used as a simple and effective preoperative indicator for the prediction of fUTI in patients undergoing PCNL.Keywords: percutaneous nephrolithotomy, febrile urinary tract infection, neutrophil–lymphocyte ratio

Cai Yang, Jiafeng Xiao, Zibei Xu, Zehong Wang Department of Laboratory Medicine, Medical Center Hospital of Qionglai City, Chengdu, Sichuan, 611530, People’s Republic of ChinaCorrespondence: Zehong Wang, Department of Laboratory Medicine, Medical Center Hospital of Qionglai City, Xinglin Road 172&num;, Chengdu, 611530, People’s Republic of China, Tel +86 18980006531, Fax +86 18980006531, Email zehongwang0110@163.comAbstract: Composed of over 1200 species of anaerobes and aerobes bacteria along with bacteriophages, viruses, and fungal species, the human gut microbiota (GM) is vital to health, including digestive equilibrium, immunologic, hormonal, and metabolic homeostasis. Micronutrients, usually refer to trace elements (copper, iodine, iron, selenium, zinc) and vitamins (A, C, D, E), interact with the GM to influence host immune metabolism. So far, microbiome studies have revealed an association between disturbances in the microbiota and various pathological disorders, such as anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, anxiety, depression, early-onset cancers, type 1 diabetes (T1D) and type 2 diabetes (T2D). As common conditions, thyroid diseases, encompassing Graves’ disease (GD), Graves’ orbitopathy (GO), Hashimoto’s thyroiditis (HT), benign nodules, and papillary thyroid cancer (TC), have negative impacts on the health of all populations. Following recent studies, GM might play an integral role in triggering diseases of the thyroid gland. Not only do environmental triggers and genetic predisposing background lead to auto-aggressive damage, involving cellular and humoral networks of the immune system, but the intestinal microbiota interacts with distant organs by signals that may be part of the bacteria themselves or their metabolites. The review aims to describe the current knowledge about the GM in the metabolism of thyroid hormones and the pathogenesis of thyroid diseases and its involvement in the appearance of benign nodules and papillary TC. We further focused on the reciprocal interaction between GM composition and the most used treatment drugs for thyroid disorders. However, the exact etiology has not yet been known. To elucidate more precisely the mechanism for GM involvement in the development of thyroid diseases, future work is needed.Keywords: gut microbiota, Graves’ disease, Hashimoto’s thyroiditis, Graves’ orbitopathy, thyroid nodules, thyroid cancer

Jingfei Weng,1,2,&ast; Yuyao Xiao,1,&ast; Jing Liu,3,&ast; Xiaohua Liu,4 Yuqing He,2 Fei Wu,1 Xiaoyan Ni,1 Chun Yang1 1Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Radiology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 4Department of Radiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun Yang; Xiaoyan Ni, Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Tel +86 18702135336 ; +86 15201803582, Email dryangchun@hotmail.com; nixiaoyan1103@126.comPurpose: To study the MRI features (based on LI-RADS) and clinical characteristics of P53-mutated hepatocellular carcinoma (HCC) patients.Patients and Methods: This study enrolled 344 patients with histopathologically confirmed HCC (P53-mutated group [n = 196], non-P53-mutated group [n = 148]). We retrospectively evaluated the preoperative MRI features, clinical and pathologic features of the lesions and assigned each lesion according to the LI-RADS. MRI findings, clinical features, and pathologic findings were compared using the Student’s t test, χ 2 test, and multivariable regression analysis.Results: Most HCC patients were categorized as LR-5. On multivariate analysis, the Edmondson–Steiner grade (odds ratio, 2.280; 95% CI: 1.268, 4.101; p = 0.006) and rim enhancement (odds ratio, 2.517; 95% CI: 1.095, 5.784; p = 0.030) were found to be independent variables associated with P53-mutated HCC. In the group of HCC lesions with the largest tumor diameter (LTD) greater than or equal to 10mm and less than or equal to 20mm, enhancing capsule was an independent predictor of P53-mutated HCC (odds ratio, 6.200; 95% CI: 1.116, 34.449; p = 0.037). Among the HCC lesions (20 mm ˂ LTD ≤ 50 mm), corona enhancement (odds ratio, 2.102; 95% CI: 1.022, 4.322; p = 0.043) and nodule-in-nodule architecture (odds ratio, 2.157; 95% CI: 1.033, 4.504; p = 0.041) were found to be independent risk factors for P53 mutation. Among the HCC lesions (50 mm ˂ LTD ≤ 100 mm), diameter (odds ratio, 1.035; 95% CI: 1.001, 1.069; p = 0.044) and AFP ≥ 400 (ng/mL) (odds ratio, 3.336; 95% CI: 1.052, 10.577; p = 0.041) were found to be independent variables associated with P53-mutated HCC.Conclusion: Poor differentiation and rim enhancement are potential predictive biomarkers for P53-mutated HCC, while HCCs of different diameters have different risk factors for predicting P53 mutations.Keywords: liver neoplasms, magnetic resonance imaging, P53-mutated

Xiang Wen,1,&ast; Xiaohui Wu,1,&ast; Zhishan Deng,1,&ast; Fan Wu,1,2 Huajing Yang,1 Shan Xiao,1 Cuiqiong Dai,1 Changli Yang,3 Shuqing Yu,4 Ruiting Sun,1 Pixin Ran,1,2 Yumin Zhou1 1State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease & National Center for Respiratory Medicine & Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Guangzhou National Laboratory, Guangzhou, Guangdong, People’s Republic of China; 3Wengyuan County People’s Hospital, Shaoguan, People’s Republic of China; 4Lianping County People’s Hospital, Heyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yumin Zhou; Pixin Ran, Email zhouyumin410@126.com; pxran@gzhmu.edu.cnBackground: The previous findings on the correlation between spirometry and high-density lipoprotein (HDL) cholesterol are intriguing yet conflicting. The aim of this research is to evaluate the relationship between HDL levels and spirometry as well as imaging parameters in patients with chronic obstructive pulmonary disease (COPD) in China.Methods: This study encompasses a total of 907 COPD patients. Participants with complete data from questionnaire interviews, lipid profile examinations, spirometry testing, and computed tomography (CT) scans were included in the analysis. A generalized additive model was employed to identify the non-linear relationship between HDL levels and both spirometry and imaging parameters. In the presence of non-linear correlations, segmented linear regression model was applied to ascertain threshold effects.Results: After adjusting for various factors, we found a non-linear correlation between HDL levels and spirometry/imaging parameters, with an inflection point at 4.2 (66 mg/dL). When Ln (HDL) was below 4.2, each unit increase correlated significantly with reduced post-bronchodilator FEV1 (0.32L, 95% CI: 0.09– 0.55), decreased predicted FEV1% (11.0%, 95% CI: 2.7– 19.3), and lowered FEV1/FVC (8.0%, 95% CI: 4.0– 12.0), along with notable increases in Ln (LAA− 950) by 1.20 (95% CI: 0.60– 1.79) and Ln (LAA− 856) by 0.77 (95% CI: 0.37– 1.17). However, no significant associations were observed when Ln (HDL) was greater than or equal to 4.2.Conclusion: A non-linear correlation existed between HDL levels with lung function and CT imaging in COPD patients. Prior to reaching 66 mg/dL, an elevation in HDL was significantly associated with impaired lung function, more severe gas trapping and emphysema.Keywords: COPD, high-density lipoprotein, lung function, computed tomography imaging

Xin Qiu,1,2,&ast; Shuang Shen,1,&ast; Donghong Lu,2 Nizhen Jiang,3 Yifei Feng,3 Jindu Li,1 Chenglei Yang,1 Bangde Xiang1,4,5 1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 3Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 4Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning, People’s Republic of China; 5Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bangde Xiang; Chenglei Yang, Email xiangbangde@gxmu.edu.cn; chenglei2017yang@163.comBackground: Hepatocellular carcinoma (HCC) presents a significant global health challenge due to its poor prognosis and high recurrence rates post-surgery. This study examines the predictive efficacy of the Advanced Lung Cancer Inflammation Index (ALI) in assessing the post-hepatectomy prognosis of patients with HCC.Methods: A cohort comprising 1654 HCC patients who underwent hepatectomy at Guangxi Medical University Cancer Hospital from 2013 to 2019 was enrolled. Patients were stratified into two groups according to the median ALI level, and then subjected to propensity score matching (PSM) in a 1:1 ratio. Kaplan-Meier survival curves, the traditional Cox proportional hazards (CPH) model, and machine learning (ML) models were employed to analyze and evaluate ALI’s prognostic significance. Furthermore, ALI’s prognostic value in digestive system tumors was validated via analysis of the National Health and Nutrition Examination Survey (NHANES) database.Results: After applying PSM, a final cohort of 1284 patients, categorized into high and low ALI groups, revealed a significantly reduced survival time in the low ALI cohort. Univariate and multivariate Cox analyses identified ALI, BCLC stage, CK19, Hepatitis B virus (HBV) DNA, lymph node metastasis, and microvascular invasion (MVI) as independent predictors of prognosis. Both traditional CPH and ML models incorporating ALI demonstrated excellent predictive accuracy, validated through calibration curves, time-dependent ROC curves, and decision curve analysis. Furthermore, the prognostic value of ALI in digestive tumors was confirmed in the NHANES database.Conclusion: The ALI exhibits potential as a prognostic predictor in patients with HCC following hepatectomy, providing valuable insights into postoperative survival.Keywords: advanced lung cancer inflammatory index, ALI, hepatocellular carcinoma, HCC, prognosis, Cox regression, machine learning, ML

Yi Zhu,1,2,&ast; Meiling Chen,3,&ast; Chuangzan Yang,1,2 Geng Lu,1,2 Sa Huang,1,2 Meili Chen,3 Yufei Wang,4 Junfeng Ban1– 3 1Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2The Innovation Team for Integrating Pharmacy with Entrepreneurship, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 3Guangdong Laboratory Animals Monitoring Institute, Guangdong Provincial Key Laboratory of Laboratory Animals, Guangzhou, People’s Republic of China; 4Analytical and Testing Center of Guangzhou University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yufei Wang; Junfeng Ban, Email yufei_wang@gzhu.edu.cn; banjunfeng@163.comPurpose: Oral drug administration is the most common and convenient route, offering good patient compliance but drug solubility limits oral applications. Celecoxib, an insoluble drug, requires continuous high-dose oral administration, which may increase cardiovascular risk. The nanostructured lipid carriers prepared from drugs and lipid excipients can effectively improve drug bioavailability, reduce drug dosage, and lower the risk of adverse reactions.Methods: In this study, we prepared hyaluronic acid-modified celecoxib nanostructured lipid carriers (HA-NLCs) to improve the bioavailability of celecoxib and reduce or prevent adverse drug reactions. Meanwhile, we successfully constructed a set of FDA-compliant biological sample test methods to investigate the pharmacokinetics of HA-NLCs in rats.Results: The pharmacokinetic analysis confirmed that HA-NLCs significantly enhanced drug absorption, resulting in an AUC0-t 1.54 times higher than the reference formulation (Celebrex®). Moreover, compared with unmodified nanostructured lipid carriers (CXB-NLCs), HA-NLCs enhance the retention time and improve the drug’s half-life in vivo.Conclusion: HA-NLCs significantly increased the bioavailability of celecoxib. The addition of hyaluronic acid prolonged the drug’s in vivo duration of action and reduced the risk of cardiovascular adverse effects associated with the frequent administration of oral celecoxib. Keywords: nanostructured lipid carriers, celecoxib, HPLC-MS/MS, pharmacokinetics

Li-Ping Ou,&ast; Yong-Jian Liu,&ast; Shi-Tong Qiu,&ast; Chen Yang, Ji-Xin Tang, Xiao-Yu Li, Hua-Feng Liu, Zhen-Nan Ye Institute of Nephrology, and Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, and Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen-Nan Ye; Hua-Feng Liu, Email yezhennan12@mails.ucas.ac.cn; liuhf@gdmu.edu.cnAbstract: Metabolic reprogramming contributes to the progression and prognosis of various kidney diseases. Glutamine is the most abundant free amino acid in the body and participates in more metabolic processes than other amino acids. Altered glutamine metabolism is a prominent feature in different kidney diseases. Glutaminolysis converts glutamine into the TCA cycle metabolite, alpha-ketoglutarate, via a cascade of enzymatic reactions. This metabolic pathway plays pivotal roles in inflammation, maladaptive repair, cell survival and proliferation, redox homeostasis, and immune regulation. Given the crucial role of glutaminolysis in bioenergetics and anaplerotic fluxes in kidney pathogenesis, studies on this cascade could provide a better understanding of kidney diseases, thus inspiring the development of potential methods for targeted therapy. Emerging evidence has shown that targeting glutaminolysis is a promising therapeutic strategy for ameliorating kidney disease. In this narrative review, equation including keywords related to glutamine, glutaminolysis and kidney are subjected to an exhaustive search on Pubmed database, we identified all relevant articles published before 1 April, 2024. Afterwards, we summarize the regulation of glutaminolysis in major kidney diseases and its underlying molecular mechanisms. Furthermore, we highlight therapeutic strategies targeting glutaminolysis and their potential clinical applications.Keywords: glutamine, glutaminolysis, kidney diseases, therapeutic target

Yu-Kai Li,1,&ast; Song Wu,2,&ast; Yu-Shan Wu,3,&ast; Wei-Hu Zhang,4,&ast; Yan Wang,5,&ast; Yue-Hua Li,1,&ast; Qiang Kang,1,&ast; Song-Quan Huang,1,&ast; Kai Zheng,1 Gai-Ming Jiang,1 Qing-Bo Wang,1 Yu-Bo Liang,1 Jin Li,1 Yawhan Lakang,1 Chen Yang,1 Jing Li,1 Jia-Ping Wang,4 Xiang Kui,5 Yang Ke1,6,7 1Department of Hepato-Biliary-Pancreatic, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 2Preventive Medicine Division, School of Life Science, Anhui University of Chinese Medicine, Hefei, AH, 230012, People’s Republic of China; 3The Second Clinical Medical College, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 4Department of Radiology, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 5Department of Pathology, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 6Department of Surgical Education and Research, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 7Yunnan Yunke Bio-Technology Institution, Kunming, YN, 650201, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Kui, Department of Pathology, the Second Affiliated Hospital, Kunming Medical University, No. 374 Kunrui Road, Wuhua District, Kunming, YN, 650101, People’s Republic of China, Tel +8613708729335, Email kuixiang@foxmail.com Yang Ke, Department of Hepato-Biliary-Pancreatic, the Second Affiliated Hospital, Kunming Medical University, No. 374 Kunrui Road, Wuhua District, Kunming, YN, 650101, People’s Republic of China, Tel +8615808875159, Email keyang1218@126.comBackground: The dominant artery blood supply is a characteristic of hepatocellular carcinoma (HCC). However, it is not known whether the blood supply can predict the post-hepatectomy prognosis of patients with HCC. This retrospective study investigated the prognostic value of the portal venous and arterial blood supply estimated on triphasic liver CT (as a portal venous coefficient, PVC, and hepatic arterial coefficient, HAC, respectively) in patients with HCC following hepatectomy.Methods: HCC patients who were tested by triphasic liver CT 2 weeks before hepatectomy and received R0 hepatectomy at the Second Affiliated Hospital, Kunming Medical University between January 1, 2016 and December 31, 2020, were retrospectively screened. Their PVC and HAC, and other variables were analyzed for the prediction of overall survival (OS) and recurrence-free survival (RFS) using the least absolute shrinkage and selection operator and Cox proportional hazard regression models.Results: Four hundred and nineteen patients (53.2 ± 10.6 years of age and 370 men) were evaluated. A shorter OS was independently associated with higher blood albumin and total bilirubin grade [hazard ratio (HR) 2.020, 95% confidence interval (CI) 1.534– 2.660], higher Barcelona Clinic Liver Cancer (BCLC) stage (HR 1.514, 95% CI 1.290– 1.777), PVC ≤ 0.386 (HR 1.628, 95% CI 1.149– 2.305), and HAC > 0.029 (HR 1.969, 95% CI 1.380– 2.809). A shorter RFS was independently associated with male (HR 1.652, 95% CI 1.005– 2.716), higher serum α-fetoprotein ≥ 400 ng/mL (HR 1.672, 95% CI 1.236– 2.263), higher BCLC stage (HR 1.516, 95% CI 1.300– 1.768), tumor PVC ≤ 0.386 (HR 1.641, 95% CI 1.198– 2.249), and tumor HAC > 0.029 (HR 1.455, 95% CI 1.060– 1.997).Conclusion: Tumor PVC or HAC before hepatectomy is valuable for independently predicting postoperative survival of HCC patients. Keywords: blood supply, computed tomography, hepatectomy, hepatocellular carcinoma, recurrence, survival

Hang Jin,1,2,&ast; Zhongqiang Yan,3,&ast; Xin Ge,4,&ast; Qi Wang,2 Hui Wang,2 Xinying Du,2 Hongbo Liu,2 Chaojie Yang,2 Ying Xiang,2 Sai Tian,2 Shaofu Qiu,1,2 Yu Zhou5 1School of Public Health, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Infectious Disease Control and Prevention, Center for Disease Control and Prevention of Chinese PLA, Beijing, People’s Republic of China; 3Department of Disease Prevention and Control, The Second Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 4School of Public Health, Anhui Medical University, Hefei, People’s Republic of China; 5Department of Clinical Laboratory, National Clinical Research Center for Geriatric Diseases, The Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaofu Qiu, Center for Disease Control and Prevention of Chinese PLA, Beijing, People’s Republic of China, Email qiushf0613@hotmail.com Yu Zhou, Department of Clinical Laboratory, National Clinical Research Center for Geriatric Diseases, The Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China, Email zhouy427@163.comPurpose: This study conducted an phenotypic and whole-genome sequencing analysis with Klebsiella aerogenes to elucidate its clinical epidemiological characteristics, antimicrobial resistance (AMR) phenotype, biofilm formation ability and hemolytic activity testing, AMR genes and phylogenetic relationships, so as to provide a further understanding of the intra-hospital strain transmission.Methods: Samples were collected from a hospital in Beijing between 2020 and 2022. All strains underwent bacterial identification, antimicrobial susceptibility testing (AST) using the VITEK-2 compact system. Biofilm formation ability and hemolytic activity were tested. Second-generation sequencing was applied to all strains, with those carrying the blaKPC gene were selected for third-generation sequencing. Whole-genome analysis identified resistance genes, plasmid types, MLST typing, and phylogenetic relationships. Plasmids were assembled to detect plasmid structures and AMR gene location.Results: Among the 42 K. aerogenes isolates, 21 were carbapenem-resistant K. aerogenes (CRKA). All strains exhibited strong biofilm formation and no hemolytic activity. Most were sourced from sputum (83.3%). CRKA demonstrated extensive resistance to antibiotics, particularly β-lactamase inhibitors and Cefotetan. This resistance pattern was closely associated with the presence of an IncFII(pHN7A8) plasmid, which carried multiple resistance genes, including blaKPC-2, blaCTX-M-65, blaTEM-1, rmtB and a large number of mobile elements. The majority of CRKA strains clustered within the same branch of the phylogenetic tree, exhibiting minimal single nucleotide polymorphism (0– 13 SNPs) differences, and they shared the same sequence type (ST292), resistance genes, and plasmids, originating from different departments, suggesting clonal transmission among the hospital.Conclusion: Our research reveals that the clonal transmission of CRKA occurs across various departments within the hospital. The widespread resistance observed in CRKA, attributed to the presence of blaKPC and ESBLs genes, underscores the need for heightened vigilance to prevent the further dissemination of CRKA within the hospital and, potentially, throughout the wider community.Keywords: Klebsiella aerogenes, carbapenem resistance, blaKPC-2, clonal transmission

Yi Zhang,1 Dang Liu,2 Bin Qiao,3 Yuanli Luo,3 Liang Zhang,3 Yang Cao,3 Haitao Ran,3,&ast; Chao Yang4,&ast; 1Department of Ultrasound, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Radiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Chongqing Key Laboratory of Ultrasound Molecular Imaging & Department of Ultrasound, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Radiology, Jiulongpo District People’s Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haitao Ran, Chongqing Key Laboratory of Ultrasound Molecular Imaging & Department of Ultrasound, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China, Tel +86 13512373563, Email ranhaitao@cqmu.edu.cn Chao Yang, Department of Radiology, Jiulongpo District People’s Hospital, Chongqing, People’s Republic of China, Tel +86 13883095836, Email ychaof737@163.comPurpose: To address the problem of suboptimal reactive oxygen species (ROS) production in Radiation therapy (RT) which was resulted from exacerbated tumor hypoxia and the heterogeneous distribution of radiation sensitizers.Materials and Methods: In this work, a novel nanomedicine, designated as PLGA@IR780-Bi-DTPA (PIBD), was engineered by loading the radiation sensitizer Bi-DTPA and the photothermal agent IR780 onto poly(lactic-co-glycolic acid) (PLGA). This design leverages the tumor-targeting ability of IR780 to ensure selective accumulation of the nanoparticles in tumor cells, particularly within the mitochondria. The effect of the photothermal therapy-enhanced radiation therapy was also examined to assess the alleviation of hypoxia and the enhancement of radiation sensitivity.Results: The PIBD nanoparticles exhibited strong capacity in mitochondrial targeting and selective tumor accumulation. Upon activation by 808 nm laser irradiation, the nanoparticles effectively alleviated local hypoxia by photothermal effect enhanced blood supplying to improve oxygen content, thereby enhancing the ROS production for effective RT. Comparative studies revealed that PIBD-induced RT significantly outperformed conventional RT in treating hypoxic tumors.Conclusion: This design of tumor-targeting photothermal therapy-enhanced radiation therapy nanomedicine would advance the development of targeted drug delivery system for effective RT regardless of hypoxic microenvironment.Keywords: Bi-DTPA, IR780, radiotherapy, tumor microenvironment hypoxia, photothermal therapy

Hyun Ji Cha,1,&ast; Chang-Hyun Han,2,3,&ast; Ju Hyun Jeon,1 Jeong Kyo Jeong,1 In Chul Jung,4 Changsop Yang,2 Byoung-Kab Kang,2 Min Ji Kim,5 Young Eun Choi,5 Young Il Kim1 1Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea; 2Korean Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 3Korean Convergence Medicine, University of Science & Technology (UST), Campus of Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 4Department of Oriental Neuropsychiatry, College of Korean Medicine, Daejeon University, Daejeon, Republic of Korea; 5Clinical Research Coordinating Team, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Young Il Kim, Tel +82-42-470-9137, Email omdkim01@dju.krPurpose: Pharmacopuncture therapy has been used in the conservative treatment of rotator cuff disease adjuvant to acupuncture treatment. Despite the increasing utilization of pharmacopuncture therapy, there is still a lack of high-quality research to support its effectiveness. This pilot study aimed to assess the feasibility of pharmacopuncture therapy adjuvant to acupuncture treatment for rotator cuff disease.Patients and Methods: This was a parallel-grouped, pragmatic randomized controlled, pilot study. Forty patients were randomly allocated to either the experimental or the control group. All patients received acupuncture treatment for four weeks, and pharmacopuncture was additionally administered to the experimental group. After eight treatments were delivered over four weeks, follow-up assessments were performed. The primary outcome was the mean change in the visual analog scale (VAS) score for shoulder pain from baseline to visit 8. Secondary outcomes included shoulder pain and disability index (SPADI) at visits 4, 8, and 9, shoulder range of motion (ROM) at visits 4, 8, and 9, EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) at visits 8 and 9, patient global impression of change (PGIC) at visits 8 and 9, and mean rescue medication consumption at visits 8 and 9.Results: Both groups showed that each treatment effectively improved rotator cuff disease in most assessments. Particularly, the group that received acupuncture plus pharmacopuncture required fewer rescue medications than the group that received acupuncture alone. However, there was little statistically significant difference between the two groups. There were no serious adverse events experienced by patients in this study.Conclusion: Although there was little statistical difference between the two groups, the combination of acupuncture and pharmacopuncture for rotator cuff disease was associated with a reduction in the rescue medicine dosage compared with acupuncture alone. Also, it confirmed the safety of pharmacopuncture therapy. This pilot study would help design future research on the effectiveness of pharmacopuncture in rotator cuff disease.Keywords: rotator cuff disease, pharmacopuncture, acupuncture, pragmatic trial, randomized controlled trial

Yan Zhang,1,&ast; Qixing Wu,2,&ast; Mingming Han,2 Chengwei Yang,2 Fang Kang,2 Juan Li,2 Chengwen Hu,1 Xia Chen1 1Department of Nursing, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xia Chen; Chengwen Hu, Email chenxiaahslyy@163.com; huchengwen318@126.comObjective: Frailty, representing the physiological reserve and tolerance of the body, serves as a crucial evaluation index of the overall status of the older adults. This study aimed to investigate the prevalence of preoperative frailty and its impact on postoperative outcomes among older adults with lumbar degenerative disease in China.Patients and Methods: In this prospective study, a total of 280 patients aged 60 and above, diagnosed with lumbar degenerative disease and scheduled for surgical intervention were enrolled. The prevalence of frailty pre-surgery was evaluated using the Tilburg Frailty Indicator (TFI) and the modified Frailty Index 11 (mFI-11). The primary outcome was postoperative complication within 30 days post-surgery. The secondary outcomes were the length of hospital stay, hospital costs, reoperation within 30 days post-surgery and unplanned readmission within 30 days post-discharge. Both univariable and multivariable logistic regression were employed to screen and identify the risk factors predisposing patients to postoperative complications.Results: A total of 272 older adults were included in the study ultimately. The frailty detection rates of TFI and mFI-11 were 15.8% (43/272) and 10.7% (29/272) respectively. Thirty-four patients (12.5%) encountered complications. Significantly elevated rates of complications, prolonged hospital stays, increased hospital costs, and heightened readmission rates were observed in the frail group compared to the non-frail group (P< 0.05). Univariable analysis showed that the potential factors related to complications are TFI, mFI-11 and albumin. Multivariable logistic regression revealed that TFI was an independent risk factor for postoperative complications (OR=5.371, 95% CI: 2.338– 12.341, P < 0.001).Conclusion: Frailty was an independent predictor of postoperative complications in older adults undergoing lumbar fusion surgery. Frailty assessment should be performed in such patients to improve preoperative risk stratification and optimize perioperative management strategies.Keywords: lumbar degenerative disease, older adults, frailty, postoperative outcome

Chengzhang Yang,1,2,&ast; Weifang Liu,2,3,&ast; Zijia Tong,1,&ast; Fang Lei,3,4 Lijin Lin,2,3 Xuewei Huang,3,5 Xingyuan Zhang,3,6 Tao Sun,2,3 Gang Wu,1 Huajing Shan,1 Shaoze Chen,1 Hongliang Li2,3 1Department of Cardiology, Huanggang Central Hospital, Huanggang, People’s Republic of China; 2Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Institute of Model Animal, Wuhan University, Wuhan, People’s Republic of China; 4Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 5Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 6School of Basic Medical Science, Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongliang Li, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China, Tel/Fax +86-27-68759302, Email lihl@whu.edu.cn Shaoze Chen, Department of Cardiology, Huanggang Central Hospital, Huanggang, People’s Republic of China, Tel/Fax +86-713-8381191, Email chenshaoze@hgyy.org.cnAim: The evidence on the association between insulin resistance (IR) and the prevalence or incidence of cardiac dysfunction has been controversial, and the relationship between pre-diabetic IR and cardiac function is lacking. Large sample studies in the Chinese general population are urgently needed to explore the association between IR and the risk of left ventricular hypertrophy (LVH) and decreased left ventricular diastolic function with preserved ejection fraction (LVDFpEF).Methods: Based on a National Health Check-up database in China, we conducted a multicenter cross-sectional retrospective study in 344,420 individuals. Furthermore, at a single center, we performed two retrospective longitudinal studies encompassing 8270 and 5827 individuals to investigate the association between IR and the development of new-onset LVH and LVDFpEF, respectively. The median follow-up duration exceeded 2.5 years. The triglyceride and glucose (TyG) index, known for its high sensitivity in detecting IR, serves as a reliable alternative marker of IR. The logistic and cox proportional hazard regression models were used to determine the relationships.Results: In the cross-sectional study, IR showed a positive association with the prevalence of LVH and decreased LVDFpEF after adjusting for confounders. In the longitudinal cohort, IR was also correlated with the new onset of LVH and decreased LVDFpEF, with hazard ratios (HR) of 1.986 (95% CI: 1.307, 3.017) and 1.386 (95% CI: 1.167, 1.647) in the fourth quartile of TyG levels compared to the lowest quartile, respectively, after adjusting for confounders. The subgroup analysis in non-hypertensive or non-diabetic people and the sensitivity analysis in the population with homeostasis model assessment of insulin resistance (HOMA-IR) further verified the above-mentioned results.Conclusion: IR was associated with LVH and decreased LVDFpEF. Effective management of IR may prevent or delay the development of adverse LVH and decreased LVDFpEF.Keywords: insulin resistance, triglyceride and glucose index, left ventricular hypertrophy, left ventricular diastolic function

Qiuyue Zhang,1– 5,&ast; Qi Zhang,6,&ast; Zhiyu Duan,2– 5,7 Pu Chen,2– 5 Jing-jing Chen,2– 5 Ming-xv Li,8 Jing-jie Zhang,9 Yan-hong Huo,10 Wu-xing Zhang,11 Chen Yang,12 Yu Zhang,12 Xiangmei Chen,2– 5 Guangyan Cai2– 5 1Chinese PLA Medical School, Beijing, People’s Republic of China; 2Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3National Key Laboratory of Kidney Diseases, Beijing, People’s Republic of China; 4National Clinical Research Center for Kidney Diseases, Beijing, People’s Republic of China; 5Beijing Key Laboratory of Kidney Diseases Research, Beijing, People’s Republic of China; 6Department of Nephrology, Capital Medical University Electric Power Teaching Hospital, Beijing, People’s Republic of China; 7Department of Nephrology, Fourth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 8Department of Nephrology, Sixth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 9Department of Nephrology, Third Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 10Department of Nephrology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 11Department of Nephrology, Eighth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 12School of Medicine, Nankai University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangyan Cai, Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Hospital 28 Fuxing Road, Beijing, 100853, People’s Republic of China, Email caiguangyan@sina.comPurpose: The International IgA Nephropathy Prediction Tool (IIgAN-PT) can predict the risk of End-stage renal disease (ESRD) or estimated glomerular filtration rate (eGFR) decline ≥ 50% for adult IgAN patients. Considering the differential progression between older adult and adult patients, this study aims to externally validate its performance in the older adult cohort.Patients and Methods: We analyzed 165 IgAN patients aged 60 and above from six medical centers, categorizing them by their predicted risk. The primary outcome was a ≥ 50% reduction in estimated glomerular filtration rate (eGFR) or kidney failure. Evaluation of both models involved concordance statistics (C-statistics), time-dependent receiver operating characteristic (ROC) curves, Kaplan–Meier survival curves, and calibration plots. Comparative reclassification was conducted using net reclassification improvement (NRI) and integrated discrimination improvement (IDI).Results: The study included 165 Chinese patients (median age 64, 60% male), with a median follow-up of 5.1 years. Of these, 21% reached the primary outcome. Both models with or without race demonstrated good discrimination (C-statistics 0.788 and 0.790, respectively). Survival curves for risk groups were well-separated. The full model without race more accurately predicted 5-year risks, whereas the full model with race tended to overestimate risks after 3 years. No significant reclassification improvement was noted in the full model without race (NRI 0.09, 95% CI: − 0.27 to 0.34; IDI 0.003, 95% CI: − 0.009 to 0.019).Conclusion: : Both models exhibited excellent discrimination among older adult IgAN patients. The full model without race demonstrated superior calibration in predicting the 5-year risk.Keywords: IgAN Progression, statistical validation, risk analysis, progression risk, prediction models, older adults

Fang Liu,1,&ast; XuYong Yang,2,&ast; Zhaohui He,1 Chenghong OuYang,1 Xiaogang Yang,1 Chunli Yang1 1Department of Intensive Care Unit, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, People’s Republic of China; 2Department of Pediatrics, Gaoxin Hospital of The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaogang Yang; Chunli Yang, Department of intensive care unit, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, People’s Republic of China, Email JXSRMICU@163.com; 434533590@qq.comBackground: In addition to the well-known Whipple’s disease (WD), Tropheryma Whipplei (TW) can also lead to acute pneumonia. There is no unified consensus on the susceptible population, pathogenesis, clinical manifestations, diagnostic criteria, and treatment options for TW pneumonia.Clinical Presentation and Intervention: This is an elderly patient with multiple injuries caused by falling from a building, and was transferred to intensive care unit (ICU) for mechanical ventilation and empirical anti-infection treatment due to severe pneumonia, and then the results of targeted next-generation sequencing (tNGS) in patient’s bronchoalveolar lavage fluid (BALF) suggested TW and human metapneumovirus (HMPV) infection, and after switching to anti-infective therapy for TW, the patient was successfully extubated and transferred out of the ICU.Conclusion: This is the first case of using tNGS to diagnose severe pneumonia caused by TW and HMPV. We hope that our study can serve as a reference for the diagnosis and treatment of related cases in the future.Keywords: Tropheryma Whipplei, bronchoalveolar lavage fluid, targeted next-generation sequencing, human metapneumovirus

Chen Yang,1,2,&ast; Wangjun Dong,2,&ast; Jianbo Luo,2 Mengzhao Ma,2 Yeyue Gao,2 Lijie Ni,2 Huixing Liu,2 Chengjun Cha,2 Yangli Xiao,2 Shaoqiang Huang1 1Department of Anesthesia, Obstetrics & Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Anesthesia, Yongping County People’s Hospital, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaoqiang Huang, Department of Anesthesia, Obstetrics & Gynecology Hospital, Fudan University, 128&num; Shenyang Road, Shanghai, 200090, People’s Republic of China, Email Drhuangsq@163.comObjective: Alterations in altitude can lead to an augmented requirement for local anesthesia among patients. Nevertheless, the necessity for an elevated dosage of local anesthetic for parturients at moderately high altitudes during spinal anesthesia for cesarean section remains uninvestigated. This up-down sequential study endeavors to determine the ED50 dose of bupivacaine required for spinal anesthesia during cesarean sections at moderately high-altitude.Methods: Thirty singleton parturients at moderately high altitude underwent elective cesarean section under combined spinal-epidural anesthesia. The up-and-down sequential method was employed, starting with an initial dose of 12mg (1.6mL) of 0.75% hyperbaric bupivacaine for the first participant. The dose for the next case was adjusted up or down by 0.75mg based on the effectiveness of the previous participant. Effectiveness was defined as the bilateral sensory block reaching T6 within 15 minutes after spinal anesthesia injection, without the need for additional epidural anesthesia before fetal delivery. The ED50 dose and 95% confidence interval were calculated using the Dixon sequential method and isotonic regression, respectively. The incidence of maternal hypotension, nausea, and vomiting during the study period was also recorded.Results: The ED50 of hyperbaric bupivacaine for spinal anesthesia in cesarean section was calculated as 8.23 mg (95% CI, 6.52– 9.32 mg) using the Dixon up-and-down method. Further validation using isotonic regression yielded a value of 8.39 mg (95% CI, 7.48– 9.30 mg), confirming the accuracy and sensitivity of the conclusion. During the operation, only 6 parturients experienced hypotension, and no adverse reactions such as nausea, vomiting, and shivering were observed.Conclusion: The ED50 dose of 0.75% hyperbaric bupivacaine for spinal anesthesia during cesarean section at moderately high altitude is 8.23 mg, which exceeds the ED50 dose typically required by parturients at low altitude. Comprehensive investigations are warranted to ascertain the ED90 or ED95 dose of local anesthetics for cesarean section at moderately high altitudes, thereby offering enhanced guidance for clinical practice.Keywords: bupivacaine, high altitude, spinal anesthesia, ED50 dose

Wei Liao,1,2,&ast; Jiaxuan Lu,3,&ast; Yuyuan Xu,4,&ast; Chulin Yang,1,5 Hongjie Chen,4 Shaohang Cai,4 Lili Liu,1,6 Shuwei Chen1,5 1State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 2Department of Intensive Care Unit, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 3Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 4Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 5Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 6Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaohang Cai, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Email shaohangcai@foxmail.com Shuwei Chen, Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, Dongfeng East Road, Guangzhou, 510060, People’s Republic of China, Email chenshuw@sysucc.org.cnBackground: To compare and analyze the presence of CD4+ and CD8 + lymphocyte infiltrates in Oral squamous cell carcinoma (OSCC) tissue versus adjacent tissue and their clinical significance.Methods: We enrolled a total of 152 patients diagnosed with OSCC, all of whom had confirmed diagnoses through pathological reports. Clinical and demographics data were extracted from medical records. Tissue microarrays were constructed and immunohistochemical staining for CD4 and CD8 was performed.Findings: The average number of infiltrating CD4+ T cells in OSCC tumor tissue was 1026.22± 1163.36 cells/mm2, which did not significantly differ from the count in adjacent tissue, which was 1163.36± 1013.23 cells/mm2. However, the number of CD8+ T cell infiltration in tumor tissue was significantly higher than in adjacent tissue (655.25± 705.70 vs 504.56± 659.26 cells/mm2, p = 0.026). We observed that, among patients who consumed alcohol, the CD4+ T cell infiltration in tumor tissue being significantly lower than that in adjacent tissue (P=0.036). Moreover, the CD8+ T cell infiltration in cancer tissue was significantly higher than in adjacent tissue for T1-2 patients (p=0.005). Patients with higher CD8+ T cell in tumor tissue exhibited significantly improved overall survival (p = 0.043). Multivariate analyses revealed that alcohol consumption had a significant impact on the number of CD4+T lymphocytes in tumor tissue (OR = 0.403, P = 0.033) while T stage was the independent factor affecting CD8+ T lymphocyte infiltration in tumor tissue (OR = 0.459, P = 0.031).Interpretation: OSCC patients with a higher number of CD8+ T lymphocyte infiltration in tumor tissue exhibited an improved prognosis.Keywords: microenvironment, OSCC, CD8 T cells, CD4 T cells, prognosis

Chenhua Yang,1 Fengling Huang,2 Huiqin Fang,3 Yunhua Zang1 1General Medicine, Bao’an Authentic TCM Therapy Hospital, Shenzhen, Guangdong, People’s Republic of China; 2College of Traditional Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 3The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Yunhua Zang, Bao’an Authentic TCM Therapy Hospital, No. 99, Lai’an Road, Xixiang Street, Bao’an District, Shenzhen, Guangdong, 518101, People’s Republic of China, Email 2209162836@qq.comPurpose: This study aimed to investigate the intervention mechanism of Jiawei Shengjiangsan (JWSJS) on kidney injury in diabetic nephropathy mice.Methods: Thirty 8-week-old db/db mice were randomly divided into five groups: model group, Perindopril group, and JWSJS low-, medium-, and high-dose groups (n=6 per group) based on body weight. Additionally, a blank control group was established consisting of 6 db/m mice aged 8 weeks. The blank and model groups received daily intragastric administration of 7g/kg/d pure water. The remaining groups were assigned to JWSJS low (3.5g/kg/d), medium (7g/kg/d), high (14g/kg/d) dosage groups, and perindopril positive control group (0.48mg/kg/d) for 12 weeks. Post-experiment, serum creatinine (SCr) and blood urea nitrogen (BUN) were analyzed using an automatic biochemical analyzer. Enzyme-linked immunosorbent assay (ELISA) measured 24-hour urinary albumin, neutrophil gelatinase-associated lipocalin (NGAL), TNF-α, IL-1β, VCAM-1, MCP-1, and HbA1c. Western blot assessed the protein expressions of p-PI3K, p-Akt, and p-NF-κB p65, while pathological kidney changes were observed.Results: Compared to the blank group, the model group exhibited increased SCr, BUN, 24-hour urinary albumin, serum NGAL, TNF-α, IL-1β, VCAM-1, MCP-1, HbA1c, p-PI3K, and p-Akt, alongside increased p-NF-κB p65 expression, indicating significant kidney pathology. After treatment, the JWSJS group showed decreased SCr, BUN, 24-hour urinary microalbumin, NGAL, HbA1c, TNF-α, IL-1β, VCAM-1, MCP-1 levels, increased p-PI3K and p-Akt expression (P< 0.05), and reduced p-NF-κB p65 content (P< 0.05). Histopathological analysis revealed that JWSJS ameliorated renal tubular epithelial cell damage, glomerular capillary and basement membrane injuries, and facilitated the repair of damaged podocytes in diabetic nephropathy mice.Conclusion: JWSJS demonstrated efficacy in reducing renal inflammation in diabetic nephropathy mice, with its mechanism likely associated with the inhibition of the PI3K/Akt/NF-κB signaling pathway.Keywords: Jiawei Shengjiangsan, diabetic nephropathy, PI3K/Akt/NF-κB signaling pathway, db/db mice, inflammation

Abstract Automated coronary angiography assessment requires precise vessel segmentation, a task complicated by uneven contrast filling and background noise. Our research introduces an ensemble U-Net model, SE-RegUNet, designed to accurately segment coronary vessels using 100 labeled angiographies from angiographic images. SE-RegUNet incorporates RegNet encoders and squeeze-and-excitation blocks to enhance feature extraction. A dual-phase image preprocessing strategy further improves the model's performance, employing unsharp masking and contrast-limited adaptive histogram equalization. Following fivefold cross-validation and Ranger21 optimization, the SE-RegUNet 4GF model emerged as the most effective, evidenced by performance metrics such as a Dice score of 0.72 and an accuracy of 0.97. Its potential for real-world application is highlighted by its ability to process images at 41.6 frames per second. External validation on the DCA1 dataset demonstrated the model's consistent robustness, achieving a Dice score of 0.76 and an accuracy of 0.97. The SE-RegUNet 4GF model's precision in segmenting blood vessels in coronary angiographies showcases its remarkable efficiency and accuracy. However, further development and clinical testing are necessary before it can be routinely implemented in medical practice.

Chaoping Yang,1,&ast; Jing Xie,2,&ast; Qianjun Chen,2 Qiongyin Yuan,3 Jianping Shang,4 Haibo Wu,5 Youhua Yang,6 Mingfang Wang,7 Xiaolan Shu,8 Jing Yue,9 Danna Tu,10 Ying Lin,1,&ast; Ronghao Zheng,4,&ast; Xiaolin Wu4 1Nursing Department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 3Obstetrical department, Huanggang Maternal and Child Health Hospital, Hubei, People’s Republic of China; 4Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5School of Health and Nursing, Wuchang University of Technology, Wuhan, People’s Republic of China; 6Department of Basic Medical Sciences, School of Medicine, Jianghan University, Wuhan, People’s Republic of China; 7Department of Pediatric Gastroenterology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 8Department of Pediatric Intensive Care Unit (PICU), Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 9Emergency Department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 10Department of Pediatric Cardiology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ronghao Zheng, Department of Pediatric Nephrology, Rheumatology, and Immunology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, 745 Wu Luo Road, Hongshan District, Wuhan, Hubei Province, 430070, People’s Republic of China, Email hytwo2001@126.com Ying Lin, Nursing department, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China, Email 523933025@qq.comPurpose: The knowledge, attitude, and practices (KAP) concerning antibiotics by healthcare students have the potential impact on controlling antibiotic abuse and antimicrobial resistance (AMR) growth. This study aims to evaluate the levels and explore the associated factors with KAP on antibiotic use and AMR in Chinese nursing students.Methods: A cross-sectional survey using a self-administered questionnaire consisting of demographics and selected features and KAP on antibiotic use and AMR was conducted to measure KAP levels among nursing students at various universities in Hubei Province, China. The logistic regression analyses were performed to analyze the potential factors associated with the KAP.Results: The survey eventually included a total of 1959 nursing students. The mean scores for KAP were 57.89 ± 26.32, 55.00 ± 12.50, and 71.88 ± 15.63, respectively. Regarding knowledge, 54.3% of participants were unaware that antibiotic was ineffective against viral infections. Regarding attitude, 36% of participants agreed that current antibiotic abuse existed; 96.2% of participants thought it necessary to set up a special course on antibiotics. Regarding practice, only 48.4% of participants usually purchased antibiotics with a prescription. Multivariable analyses indicated that lack of discussion on AMR in school courses was an independent risk factor against KAP, respectively. The main knowledge sources of antibiotic being outside the classroom was an independent risk factor related to knowledge and practice. The average score > 80 points was an independent protective factor related to knowledge and practice.Conclusion: The KAP level on antibiotic use and AMR among Hubei nursing students was general and required further strengthening. Nursing students with risk factors should be prioritized in educational interventions. The findings of our study pointed out some directions for tailored interventions to improve the training on antibiotics.Keywords: antibiotic use, antimicrobial resistance, knowledge, attitude, practice, nursing students

Chunyan Yang,&ast; Hao Tian,&ast; Guixing Xu, Qin Luo, Mingsheng Sun, Fanrong Liang Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fanrong Liang, Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, No. 37 Shi’er Qiao Road, Chengdu, Sichuan, 610075, People’s Republic of China, Email acuresearch@126.comPurpose: The effect of acupuncture as adjunctive therapy for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) was controversial. Thus, we aimed to evaluate the effects of acupuncture for treating AECOPD.Methods: Eight databases were searched from database inception to July 30, 2023. All RCTs compared acupuncture plus conventional western medicine with conventional western medicine alone were included. Outcomes were quality of life, lung function, blood oxygen condition, exercise capacity, daily symptoms, duration of hospitalization, and adverse events. The statistical analyses were conducted using Stata 17.0, and methodological quality was measured by the Cochrane bias risk assessment tool. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence.Results: Twelve studies including 915 patients were included. Compared with conventional western medicine alone, acupuncture combined with conventional western therapy significantly improved quality of life (CAT: MD: − 3.25; 95% CI: − 3.73 to − 2.78, P< 0.001) and arterial blood gas (PaCO2: MD: − 1.85; 95% CI: − 2.74 to − 0.95, P< 0.001; PaO2: MD: 5.15; 95% CI: 1.22 to 9.07, P = 0.01). And for lung function, statistical benefits were found in FEV1/FVC (MD: 4.66; 95% CI: 2.21 to 7.12, P< 0.001), but no difference was seen for FEV1% (MD: 1.83; 95% CI: − 0.17 to 3.83, P = 0.073). There was no significant improvement in exercise capacity (6MWD: MD: 96.69; 95% CI: − 0.60 to 193.98, P = 0.051), hospitalization duration (MD: − 5.70; 95% CI: − 11.97 to 0.58, P = 0.075), and dyspnea (mMRC: MD: − 0.19; 95% CI: − 0.61 to 0.63, P = 0.376) between two groups. Overall bias for CAT and mMRC was in “high” risk, FEV1%, FEV1/FVC, PaCO2, and PaO2 was in “some concern” and 1 RCT assessing hospitalization duration was in “low” risk. And the overall assessments were either moderate, low or very low certainty. Seven trials performed safety assessment of acupuncture, and no serious adverse events were reported.Conclusion: Acupuncture might have auxiliary effects on AECOPD. However, the quality of the evidence is limited, and more high-quality RCTs are needed to be performed in the future.Keywords: acute exacerbation of chronic obstructive pulmonary disease, acupuncture, systematic review, meta-analysis

Yiling Lin,1,2 Yingneng Zhang,1,2 Xia Cai,3 Huashen He,2 Chuangzan Yang,2 Junfeng Ban,1,2,4 Bohong Guo1 1School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2The Innovation Team for Integrating Pharmacy with Entrepreneurship, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 3Guangdong Institute for Drug Control, Guangzhou, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaCorrespondence: Junfeng Ban; Bohong Guo, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 51006, People’s Republic of China, Tel +86 20 39352309, Email banjunfeng@163.com; bohong-g@163.comBackground: Delayed wound healing in skin injuries has become a significant problem in clinics, seriously affecting and even threatening life and health. Recently, research interest has increased in developing wound dressings containing bioactive compounds capable of improving outcomes for complex healing needs.Methods: In this study, Puerarin-loaded nanoparticles (Pue-NPs) were prepared using the cell-penetrating peptide-poly (lactic-co-glycolic acid) (CPP-PLGA) as a drug carrier by the emulsified solvent evaporation method. Then, they were added into poly (acrylic acid) to obtain a self-assembled nanocomposite hydrogels (SANHs) drug delivery system using the co-polymerization method. The particle size, zeta potential, and micromorphology of Pue-NPs were measured; the appearance, mechanical properties, adhesive strength, and biological activity of SANHs were performed. Finally, the potential of SANHs for wound healing was further evaluated in streptozotocin-induced diabetic mice.Results: Pue-NPs were regularly spherical, with an average particle size of 134.57 ± 1.42 nm and a zeta potential of 2.14 ± 0.78 mV. SANHs was colorless and transparent with a honeycomb-like porous structure and had an excellent swelling ratio (917%), water vapor transmission rate (3077 g·m− 2·day− 1), mechanical properties (Young’s modulus of 18 kPa, elongation at break of 307%), and adhesive strength (15.5 kPa). SANHs exhibited sustained release of Pue over 48h, with a cumulative release of 55.60 ± 6.01%. In vitro tests revealed that the SANHs presented a 92.22% antibacterial rate against Escherichia coli after 4h, and a 61.91% scavenging rate of 1.1-diphenyl-2-trinitrophenylhydrazine (DPPH) radical. In vivo experiments showed that SANHs accelerated wound repair by reducing the inflammatory response at the wound site, promoting angiogenesis, and facilitating epidermal regeneration and collagen deposition.Conclusion: In conclusion, we successfully prepared SANHs. Our results show that SANHs have excellent performance and improves wound healing in diabetic mice model, indicating that it can be used to develop an effective strategy for the treatment of diabetic wounds. Keywords: Puerarin-loaded nanoparticles, nanocomposite hydrogel, drug delivery, wound healing

Peng Xu,1 Meng Li,1,2 Qi Jiang,3 Chongguang Yang,4 Xiangxiang Liu,1 Howard Takiff,5 Qian Gao1,2 1National Clinical Research Center for Infectious Diseases, Shenzhen Clinical Research Center for Tuberculosis, Shenzhen Third People’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Science, Shanghai Medical College, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, People’s Republic of China; 3Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, People’s Republic of China; 4School of Public Health (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen, People’s Republic of China; 5Laboratorio de Genética Molecular, CMBC, IVIC, Caracas, VenezuelaCorrespondence: Qian Gao, National Clinical Research Center for Infectious Diseases, Shenzhen Clinical Research Center for Tuberculosis, Shenzhen Third People’s Hospital, No. 29 Bulan Road, Longgang District, Shenzhen, Guangdong, People’s Republic of China, Tel +86-21-5423-7195, Fax +86-21-5423-7971, Email qiangao@fudan.edu.cnObjective: Drug resistance is the critical determinant for appropriate tuberculosis (TB) treatment regimens and an important indicator of the local TB burden. We aimed to investigate and compare trends in TB drug resistance in the urban Songjiang District of Shanghai from 2011 to 2020, and the rural Wusheng County of Sichuan Province from 2009 to 2020, to assess the effectiveness of local TB control and treatment programs.Methods: Whole-genome sequencing data of Mycobacterium tuberculosis were used to predict drug-resistance profiles and identify genomic clusters. Clustered, retreated cases of drug-resistant TB with identical resistance mutations, as well as all new resistant cases, were defined as transmitted resistance. The Cochran-Armitage trend test was used to identify trends in the proportions. Differences between groups were tested using the Wilcoxon rank sum or chi-square tests.Results: The annual proportions of rifampicin-resistant (RR), isoniazid-resistant (INH-R) and multidrug-resistant (MDR) TB cases did not change significantly in Songjiang. In Wusheng, however, the percentage of total TB cases that were RR decreased from 13.2% in 2009 to 3.7% in 2020, the INH-R cases decreased from 16.5% to 7.3%, and the MDR cases decreased from 10.7% to 3.7%. In retreated cases, the percentage of drug resistance decreased in both Songjiang and Wusheng, suggesting improved treatment programs. Transmitted resistance accounted for more than two thirds of drug-resistant cases over the entire study periods, and in recent years this proportion has increased significantly in Songjiang.Conclusion: In both urban Songjiang and rural Wusheng, drug-resistant TB is mostly the result of transmission of drug resistant strains and the percentage of transmitted resistance will likely increase with on-going improvements in the TB treatment programs. Reducing the prevalence of drug resistance depends principally upon decreasing transmission through the prompt diagnosis and effective treatment of drug-resistant TB cases.Keywords: tuberculosis, trends of drug resistance, whole-genome sequencing, urban and rural China

Yoona Oh,1,2,&ast; Chang-Hyun Han,3,4,&ast; Yeonhak Kim,1 Jihun Kim,1 Changsop Yang,3 Young Eun Choi,5 Byoung-Kab Kang,3 Kun Hyung Kim,1,2 Gi Young Yang,1,2 Byung Ryul Lee,1,2 Eunseok Kim1,2 1Department of Acupuncture and Moxibustion Medicine, Pusan National University Korean Medicine Hospital, Yangsan, Republic of Korea; 2Division of Clinical Medicine, School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea; 3KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 4Korean Convergence Medicine, University of Science & Technology (UST), Campus of Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 5Clinical Research Coordinating Team, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Eunseok Kim, Division of Clinical Medicine, School of Korean Medicine, Pusan National University, 49, Busandaehak-ro, Mulgeum-eup, Yangsan-si, Gyeongnam, 50612, Republic of Korea, Tel +82 55 360 5950, Fax +82 55 360 5890, Email eskim@pusan.ac.krPurpose: Pharmacopuncture therapy (PPT) combines medicinal extracts with acupuncture and is widely used as an adjunct in clinical practice. This study assessed the safety and feasibility of PPT in addition to conventional Korean Medicine treatment (CKMT), including electroacupuncture, cupping and infra-red, for lumbar spinal stenosis (LSS).Patients and Methods: Forty patients diagnosed with LSS were randomly assigned to undergo PPT with CKMT (experimental group) or CKMT alone (control group) at a 1:1 ratio, receiving 10 sessions of each intervention over five weeks. The primary clinical outcome was measured using the 100-mm Visual Analog Scale (VAS) for buttock and leg pain five weeks post-treatment. Secondary outcomes included clinically important difference (CID), Zurich Claudication Questionnaire, self-reported walking capacity, Modified–Modified Schober test, EuroQol 5-dimension 5-level questionnaire, and the patient’s global impression of change. The adverse events were assessed at each visit. The analysis of covariance was conducted to compare between two groups.Results: Intervention completion rates were 95% and 100% in the experimental and control groups, respectively. No statistically significant differences were found between groups regarding the primary outcome (adjusted mean difference: 8.0; 95% confidence interval: − 1.4– 17.4). The mean difference in the 100-mm VAS for low back pain at week 5 (adjusted mean difference: 12.9; 95% confidence interval: 2.4– 23.4) and the proportion of patients who reached the minimum CID was higher in the experimental group than in the control group. However, no significant differences were observed with other secondary outcomes. One patient in the experimental group experienced a systemic skin rash that resolved the same day, whereas the adverse events in the other group were mild and transient.Conclusion: This trial demonstrated the feasibility of add-on effects and the safety of pharmacopuncture in patients with LSS. Further studies are warranted to evaluate the add-on effects of PPT in treating LSS.Trial Registration: Clinical Research Information Service (CRIS), KCT0007229; registered on April 26, 2022.Keywords: lumbar spinal stenosis, pharmacopuncture therapy, add-on effect, conventional Korean medicine treatment, pragmatic randomized pilot trial

Xiaoqun Xu,1,&ast; Xinyu Zhu,2,&ast; Hanxin Wang,3 Xiao Liu,3 Chao Yang,3 Libin Liu,1 Tielong Chen,4 Long Cai,1 Houyong Zhu4 1Centre of Laboratory Medicine, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Houyong Zhu, Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, No. 453 Stadium Road, Hangzhou, 310007, People’s Republic of China, Email houyongzhu@foxmail.com Long Cai, Department of Clinical Laboratory, Hangzhou Red Cross Hospital, NO. 208 East Huancheng Road, Hangzhou, 310003, People’s Republic of China, Email cailong317@hotmail.comAim: The purpose of this study was to investigate the role of neutrophil-lymphocyte ratio (NLR), C-reactive protein-albumin ratio (CAR), and platelet-lymphocyte ratio (PLR) in the prognosis of patients with coronary artery disease (CAD) complicated with coronavirus disease 2019 (COVID-19).Methods: This study included 265 patients. A receiver operating characteristic (ROC) curve analysis was performed to preliminarily evaluate the predictive ability of NLR, CAR, and PLR for all-cause death. The primary outcome was all-cause death during hospitalization, while the secondary outcomes were cardiovascular death and respiratory failure death. The Cox proportional hazard model with adjusted covariates was used to analyze the cumulative risk of outcomes. We also conducted subgroup analyses based on the acute and chronic characteristics of CAD. Propensity score matching (PSM) was used to further evaluate the robustness of the primary outcome.Results: The ROC curve analysis results showed that the area under curve (AUC) values were 0.686 (95% CI 0.592– 0.781, P< 0.001) for NLR, 0.749 (95% CI 0.667– 0.832, P< 0.001) for CAR, and 0.571 (95% CI 0.455– 0.687, P=0.232) for PLR. The Cox proportional hazard model showed that trends in NLR and PLR did not affect the risk of all-cause death (P=0.096 and P=0.544 for trend, respectively), but a higher CAR level corresponded to a higher risk of all-cause death (P< 0.001 for trend). Similarly, The trends of NLR and PLR did not affect the risk of cardiovascular death and respiratory failure death, while a higher CAR level corresponded to a higher risk of cardiovascular death and respiratory failure death. The results of subgroup analyses and PSM were consistent with the total cohort.Conclusion: In patients with CAD complicated with COVID-19, a higher CAR level corresponded to a higher risk of all-cause death, cardiovascular death, and respiratory failure death, while trends in NLR and PLR did not.Keywords: coronary artery disease, coronavirus disease 2019, neutrophil-lymphocyte ratio, C-reactive protein-albumin ratio, platelet-lymphocyte ratio

Dunling Xia,1 Zongqing Lu,1 Shuai Li,1 Pu Fang,1 Chun Yang,2 Xiaoyan He,3 Qinghai You,1 Gengyun Sun1 1Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Emergency Intensive Care Unit, the First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3School of Life Sciences, Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Qinghai You; Gengyun Sun, Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Sanli’an Street, Shushan District, Hefei, Anhui Province, 230032, People’s Republic of China, Tel +86 551 6292 2913, Fax +86 551 6292 2752, Email amormor@126.com; sungengy@126.comIntroduction: Acute lung injury (ALI) and its most severe form acute respiratory distress syndrome (ARDS) are commonly occurring devastating conditions that seriously threaten the respiratory system in critically ill patients. The current treatments improve oxygenation in patients with ALI/ARDS in the short term, but do not relieve the clinical mortality of patients with ARDS.Purpose: To develop the novel drug delivery systems that can enhance the therapeutic efficacy of ALI/ARDS and impede adverse effects of drugs.Methods: Based on the key pathophysiological process of ARDS that is the disruption of the pulmonary endothelial barrier, bilirubin (Br) and atorvastatin (As) were encapsulated into an intelligent reactive oxygen species (ROS)-responsive nanocarrier DSPE-TK-PEG (DPTP) to form nanoparticles (BA@DPTP) in which the thioketal bonds could be triggered by high ROS levels in the ALI tissues.Results: BA@DPTP could accumulate in inflammatory pulmonary sites through passive targeting strategy and intelligently release Br and As only in the inflammatory tissue via ROS-responsive bond, thereby enhancing the drugs effectiveness and markedly reducing side effects. BA@DPTP effectively inhibited NF-κB signaling and NLRP3/caspase-1/GSDMD-dependent pyroptosis in mouse pulmonary microvascular endothelial cells. BA@DPTP not only protected mice with lipopolysaccharide-induced ALI and retained the integrity of the pulmonary structure, but also reduced ALI-related mortality.Conclusion: This study combined existing drugs with nano-targeting strategies to develop a novel drug-targeting platform for the efficient treatment of ALI/ARDS.Keywords: acute lung injury, acute respiratory distress syndrome, reactive oxygen species-responsiveness, nanoparticles, bilirubin, atorvastatin

Lina Guo,1 Jaclene A Zauszniewski,2 Gege Zhang,1 Xiaoyu Lei,1 Mengyu Zhang,1 Miao Wei,1 Keke Ma,1 Caixia Yang,1 Yanjin Liu,3 Yuanli Guo1 1Department of Neurology, National Advanced Stroke Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, USA; 3Department of Nursing, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Yuanli Guo, Email gylzd@163.comObjective: To explore distinct longitudinal trajectories of resourcefulness among initial ischemic stroke patients from diagnosis to 12 months, and to identify whether sociodemographic factors, disease-related factors, self-efficacy, family function, and social support can predict patterns in the trajectories of resourcefulness.Methods: A prospective longitudinal study was conducted. Initial ischemic stroke patients who met inclusion and exclusion criteria were followed up when still in hospital (Preparing for discharge, Baseline, T1), at 1 month (T2), at 3 months (T3), at 6 months (T4), at 9 months (T5) and 12 months (T6) (± 1 week) after discharge. General information, National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), General Self-Efficacy Scale (GSES), General Family Functioning Subscale (FAD-GF), and Social Support Rate Scale (SSRS) were used in T1. The Resourcefulness Scale© was evaluated at 6 time points. Growth mixture modeling was used to identify trajectory patterns of resourcefulness. Logistic regression was used to identify predictors of resourcefulness trajectories.Results: Three longitudinal trajectories of resourcefulness were identified and named as the high-stable class (38.9%, n=71), fluctuation class (41.2%, n=75), and low-stable class (19.9%, n=36), respectively. Dwelling areas (x2= 6.805, P= 0.009), education (x2= 44.865, P= 0.000), monthly income (x2= 13.063, P= 0.001), NIHSS scores (x2= 44.730, P= 0.000), mRS scores (x2= 51.788, P= 0.000), Hcy (x2= 9.345, P= 0.002), GSES (x2= 56.933, P= 0.000), FAD-GF (x2= 41.305, P= 0.000) and SSRS (x2=52.373, P= 0.000) were found to be statistically significant for distinguishing between different resourcefulness trajectory patterns. Lower education (OR=0.404), higher NIHSS(OR=6.672) scores, and higher mRS(OR=21.418) scores were found to be risk factors for lower resourcefulness, whereas higher education(OR=0.404), GSES(OR=0.276), FAD-GF(OR=0.344), and SSRS(OR=0.358) scores were identified as protective factors enhancing resourcefulness.Conclusion: This study obtained three patterns of trajectories and identified their predictive factors in initial ischemic stroke. The findings will assist health care professionals in identifying subgroups of patients and when they may be at risk of low resourcefulness and provide timely targeted intervention to promote resourcefulness.Keywords: initial ischemic stroke, resourcefulness, longitudinal study, social ecology theory, predictive factors, nursing care

Xiaoxue Yang,1– 3 Lewei Liu,1– 3 Yinghan Tian,1– 3 Cheng Yang,1– 3 Chen Ling,1– 3 Huanzhong Liu2,3 1Department of Psychiatry, School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 3Anhui Psychiatric Center, Anhui Medical University, Hefei, Anhui Province, People’s Republic of ChinaCorrespondence: Huanzhong Liu, Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China, Tel +86-551-82324616, Fax +86-551-82324252, Email huanzhongliu@ahmu.edu.cnPurpose: Insomnia is related to alexithymia in adults, but the relationship between insomnia and alexithymia in adolescents with major depressive disorder remains unclear. This study aimed to investigate the sex differences and the association between insomnia and alexithymia in adolescents with major depressive disorder.Patients and Methods: From October 2020 to April 2022, adolescent patients with major depressive disorder were recruited from psychiatric departments of seven hospitals in Anhui Province, China. Their general demographic and clinical information were collected. The 20-item Toronto Alexithymia Scale, the Center for Epidemiologic Studies of Depression Scale, and the Insomnia Severity Index Scale were used to assess their alexithymia, depression, and insomnia symptoms, respectively. The analysis of variance (ANOVA), Student’s t-test and Mann–Whitney U-test were used for continuous variables and chi-square tests for categorical variables. Pearson’s correlation analysis and Spearman correlation analysis were used to examine the correlation between ISI and demographic and clinical variables. Multiple binary logistic regression analyses with the “Enter” method were carried out to explore the correlations of insomnia.Results: The prevalence of insomnia in female adolescent patients was similar to that of male patients (χ2=1.84, p = 0.175). Compared with those without insomnia, patients with insomnia had worse family relationships (F = 7.71, p = 0.021), perceived heavier academic stress (F = 6.32, p = 0.012), more likely to take sedative-hypnotics (F = 5.51, p = 0.019), had higher levels of depression (F = 81.57, p < 0.001) and alexithymia (F = 28.57, p < 0.001). Correlation analysis showed that alexithymia was significantly associated with insomnia in adolescent patients (r = 0.360, p < 0.01). Binary logistic regression analyses showed that, alexithymia was significantly associated with insomnia in female patients (OR = 1.050, p < 0.05) but not male patients.Conclusion: In female adolescent patients, alexithymia is a risk factor of insomnia, which is of great importance in the understanding of the psychopathological mechanisms, treatments and psychological interventions of insomnia in adolescents with major depressive disorder.Keywords: adolescents, major depressive disorder, insomnia, alexithymia

Yinhui Zeng,1,&ast; Jinyuan Li,1,&ast; Yueqiang Wen,2,&ast; Haiqing Xiao,1 Chao Yang,1 Qingxiang Zeng,1 Wenlong Liu1 1Department of Otolaryngology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, People’s Republic of China; 2Department of Nephrology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenlong Liu, Department of Otolaryngology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623, People’s Republic of China, Email lwl20103@163.comPurpose: Eosinophils have pivotal roles in the development of allergic rhinitis (AR) through the release of cytotoxic substances. Apolipoprotein A-I (Apo-AI) exhibits a strong inhibitory effect on eosinophil infiltration in allergic diseases. Nevertheless, the precise impact of Apolipoprotein A-I on eosinophils remains uncertain.Methods: Our study recruited a total of 15 AR children and 15 controls. The correlation between Apo-AI expression and the counts of blood eosinophils was examined. Flow cytometry was employed to assess the role of Apo-AI in eosinophil apoptosis and adhesion. The Transwell system was performed to conduct the migration assay. An animal model using AR mice was established to test the effect of Apo-AI on eosinophils.Results: Serum Apo-AI were negatively related to eosinophils counts and eosinophil chemotactic protein levels in AR. Apo-AI exerts a pro-apoptotic effect while also impeding the processes of adhesion, migration, and activation of eosinophils. The apoptosis triggered by Apo-AI was facilitated through the phosphoinositide 3-kinase (PI3K) pathway. The chemotaxis and activation of eosinophils, which are influenced by Apolipoprotein A-I, are regulated through the PI3K and MAPK signaling pathways. Apo-AI treated mice presented with decreased blood and nasal eosinophilic inflammation as well as down-regulated eosinophil related cytokines.Conclusion: Our findings provide confirmation that Apo-AI exhibits inhibitory effects on the function of eosinophils in allergic rhinitis. This suggests that Apo-AI holds potential as a therapeutic target for future treatment strategies.Keywords: apolipoprotein A-I, eosinophils, allergic rhinitis, apoptosis, adhesion, migration, activation

Li Bao,1,2 Bowen Wu,3 Chunjing Yang,1,2 Xiqiao Xu,1,2 Zhengyuan Shi,1,2 Dechun Jiang1,2 1Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Bio-Characteristic Profiling for Evaluation of Rational Drug Use, Beijing, People’s Republic of China; 3Institute for TCM-X, MOE Key Laboratory of Bioinformatics, Bioinformatics Division, BNRIST, Department of Automation, Tsinghua University, Beijing, People’s Republic of ChinaCorrespondence: Zhengyuan Shi; Dechun Jiang, Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi-Road, Haidian District, Beijing, 10038, People’s Republic of China, Tel +86-10-63926405 ; +86-10-63926723, Email shizhengyuan2980@bjsjth.cn; jdc@bjsjth.cnPurpose: Amino acids are the important metabolites in the body and play a crucial role in biological processes. The purpose of this study is to provide a profile of amino acids change in the serum of T2DM patients and identify potential biomarkers.Patients and Methods: In this study, we quantitatively determined the serum amino acid profiles of 30 T2DM patients and 30 healthy volunteers. T test and multivariate statistical analysis were used to identify candidate biomarkers with GraphPad Prism 9.5 software and MetaboAnalyst 5.0 on-line platform.Results: Thirty-four amino acids were quantified, and 19 amino acid levels differed significantly between T2DM and Healthy groups. Screened by the specific screening criteria (VIP> 1.0; P< 0.05; FC> 1.5, or FC< 0.67) in MetaboAnalyst 5.0 platform, 8 amino acids were identified as potential biomarkers. Pearson rank correlation test showed 14 differential amino acids were significantly correlated with T2DM-related physiological parameters.Conclusion: The results of this study provide theoretical basis for the subsequent development of dietary supplements for the prevention or treatment of T2DM and its complications.Keywords: diabetes mellitus type 2, T2DM, targeted metabolomics, amino acids, biomarker

Chunmei Yang,1,2 Tingwan Du,1 Yueying Zhao,1 Youhui Qian,1 Jiashi Tang,1 Xiaohong Li,2,&ast; Ling Ma1,3,&ast; 1Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Health Management Center, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Environmental Health Effects and Risk Assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohong Li; Ling Ma, Email 1848922774@qq.com; xjml@swmu.edu.cnPurpose: To construct and validate a precise and personalized predictive model for non-alcoholic fatty liver disease (NAFLD) to enhance NAFLD screening and healthcare administration.Patients and Methods: A total of 730 participants’ clinical information and outcome measurements were gathered and randomly divided into training and validation sets in a ratio of 3:7. Using the least absolute shrinkage and selection operator (LASSO) regression and multiple logistic regression, a nomogram was established to select risk predictor variables. The NAFLD prediction model was validated through the receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA).Results: After random grouping, the cohort comprised 517 in the training set and 213 in the validation set. The prediction model employed nine of the 20 selected variables, namely gender, hypertension, waist circumference, body mass index, blood platelet, triglycerides, high-density lipoprotein cholesterol, plasma glucose, and alanine aminotransferase. ROC curve analysis yielded an area under the curve values of 0.877 (95% Confidence Interval [CI]: 0.848– 0.907) for the training set and 0.871 (95% CI: 0.825– 0.917) for the validation set. Optimal critical values were determined as 0.472 (0.786, 0.825) in the training set and 0.457 (0.743, 0.839) in the validation set. Calibration curves for both sets showed proximity to the ideal diagonal, with P-values of 0.972 and 0.370 for the training and validation sets, respectively (P > 0.05). DCA indicated favorable clinical applicability of the model.Conclusion: We constructed a nomogram model that could complement traditional NAFLD detection methods, aiding in individualized risk assessment for NAFLD.Keywords: non-alcoholic fatty liver disease, nomogram, prediction model, LASSO

Na Yong,1 Yu-Ling Ren,2 Chun-Yuan Wang,3 Cong Yang4 1Mental Health Center, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China; 2Gao Ping Middle School, Nanchong, Sichuan, 637000, People’s Republic of China; 3Bai ta Middle School, Nanchong, Sichuan, 637000, People’s Republic of China; 4Long Men Middle School, Nanchong, Sichuan, 637000, People’s Republic of ChinaCorrespondence: Na Yong, Mental Health Center, The Affiliated Hospital of North Sichuan Medical College, No. 1 Maoyuan South Road, Shunqing District, Nanchong, Sichuan, 637000, People’s Republic of China, Email nayong5000@163.comBackground: Many middle school students are depressed due to pressure from family, study, life, and communication. With the increasing depression of middle school students, professional psychological counseling institutions have also become more numerous. Therefore, students need to be guided to correctly recognize difficulties and seek professional psychological assistance.Aim: We aimed to investigate the depression status of middle school students in the city and analyze their attitude towards professional psychological help-seeking.Methods: A total of 2485 students from two classes of each grade from six middle schools in the city were randomly selected as the research objects. They were subjected to answer the general questionnaire and professional psychological help-seeking attitude questionnaire to analyze their depression status, psychological help-seeking status, and attitude towards professional psychological help-seeking.Results: 2485 questionnaires were distributed, and 2205 valid questionnaires were returned. A total of 791 (35.9%) of students had depressive symptoms. The detection rate and depression scores in girls were significantly higher than in boys, and the detection rate in junior high school students in the city was notably higher than in high school students and students from rural areas (P< 0.05). Only 31 (3.9%) middle school students with depressive symptoms have sought professional psychological help. The scores of self-cognition, stigma tolerance, interpersonal openness, and trust scores of middle school students with depressive symptoms in help-seeking attitude were significantly lower than those of normal students, while self-stigma scores were significantly higher in those with depressive symptoms (P< 0.001).Conclusion: Middle school students in the city with depression have a poor attitude towards professional psychological help-seeking. Educators should positively and correctly guide depressed middle school students to seek professional psychological assistance when they need help.Keywords: city, depression status, middle school students, professional psychological help-seeking, attitude

Caixia Yang,1,2,&ast; Yuan Ding,1,2,&ast; Zhengwei Mao,3 Weilin Wang1,2 1Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 3MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengwei Mao, Department of Polymer Science and Engineering, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou, Zhejiang, 310058, People’s Republic of China, Tel +86057187783820, Fax +86057187068001, Email zwmao@zju.edu.cn Weilin Wang, Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, Zhejiang, 310009, People’s Republic of China, Email wam@zju.edu.cnAbstract: The overall cancer incidence and death toll have been increasing worldwide. However, the conventional therapies have some obvious limitations, such as non-specific targeting, systemic toxic effects, especially the multidrug resistance (MDR) of tumors, in which, autophagy plays a vital role. Therefore, there is an urgent need for new treatments to reduce adverse reactions, improve the treatment efficacy and expand their therapeutic indications more effectively and accurately. Combination therapy based on autophagy regulators is a very feasible and important method to overcome tumor resistance and sensitize anti-tumor drugs. However, the less improved efficacy, more systemic toxicity and other problems limit its clinical application. Nanotechnology provides a good way to overcome this limitation. Co-delivery of autophagy regulators combined with anti-tumor drugs through nanoplatforms provides a good therapeutic strategy for the treatment of tumors, especially drug-resistant tumors. Notably, the nanomaterials with autophagy regulatory properties have broad therapeutic prospects as carrier platforms, especially in adjuvant therapy. However, further research is still necessary to overcome the difficulties such as the safety, biocompatibility, and side effects of nanomedicine. In addition, clinical research is also indispensable to confirm its application in tumor treatment.Keywords: autophagy, tumor resistance, nanotechnology, combination therapy, co-delivery

Chunkun Yang,1,&ast; Qinwei Zhu,2,&ast; Yanbo Chen,3,&ast; Kui Ji,2 Shuanghong Li,2 Qian Wu,1 Qingquan Pan,2 Jun Li1 1Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Department of Emergency, Weifang Hospital of Traditional Chinese Medicine, Weifang, Shandong, People’s Republic of China; 3Department of Arrhythmia, Weifang People’s Hospital, Weifang, Shandong, People’s Republic of China&ast;These authors contributed equally to this workThese authors contributed equally to this workCorrespondence: Jun Li, Email gamyylj@163.comAbstract: Cardiovascular diseases (CVDs) are the most common cause of death worldwide and has been the focus of research in the medical community. Curcumin is a polyphenolic compound extracted from the root of turmeric. Curcumin has been shown to have a variety of pharmacological properties over the past decades. Curcumin can significantly protect cardiomyocyte injury after ischemia and hypoxia, inhibit myocardial hypertrophy and fibrosis, improve ventricular remodeling, reduce drug-induced myocardial injury, improve diabetic cardiomyopathy(DCM), alleviate vascular endothelial dysfunction, inhibit foam cell formation, and reduce vascular smooth muscle cells(VSMCs) proliferation. Clinical studies have shown that curcumin has a protective effect on blood vessels. Toxicological studies have shown that curcumin is safe. But high doses of curcumin also have some side effects, such as liver damage and defects in embryonic heart development. This article reviews the mechanism of curcumin intervention on CVDs in recent years, in order to provide reference for the development of new drugs in the future.Keywords: curcumin, intima, endothelial cells, vascular smooth muscle cell, cardiovascular diseases, inflammation, apoptosis

Hongcai Yang,&ast; Tianhao Cong,&ast; Yingen Luo, Chao Yang, Jinrui Ren, Xiao Li Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao Li, Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Tel +86-13910309111, Fax +86-028-88092354, Email simonlixiao@gmail.comObjective: To investigated the association between sarcopenia and the prognosis and adverse events of hepatocellular carcinoma (HCC) patients undergoing interventional therapy combined with immunotherapy and targeted therapy.Methods: Between January 2019 and December 2022, patients with unresectable HCC who received interventional therapy combined with immunotherapy and targeted therapy were included in this study. Total skeletal muscle area at the L3 level was normalized for height in m2 as the skeletal muscle index (SMI). All patients were divided into low and high SMI group according to the median SMI.Results: Ninety-six consecutive patients were included eventually, with 49 patients in the high-SMI group and 47 patients in the low-SMI group. In the low-SMI group, the median overall survival (OS) was 459.00 days (95% CI, 334.76– 583.24 days), and the 3-, 6-, and 12-month OS rates were 100%, 89.4% and 68.1%, respectively. In the high-SMI group, the median OS was not reached, and the 3-, 6-, and 12-month OS rates were 100%, 98% and 79.5%, respectively (p< 0.05). SMI and Barcelona Clinic Liver Cancer (BCLC) C stage were independent prognostic factors for OS (p< 0.05). In the low-SMI group, 26 patients had treatment-related adverse events (TRAEs), resulting in dose adjustment or treatment suspension for 10 patients. In the high-SMI group, 33 patients had TRAEs, and 18 patients received dose adjustment or treatment suspension; the between-group difference was nonsignificant (p> 0.05).Conclusion: SMI is associated with the prognosis of HCC patients receiving interventional therapy combined with immunotherapy and targeted therapy, and sarcopenia is an independent risk factor for OS. However, sarcopenia does not seem to predict the occurrence of adverse events.Keywords: hepatocellular carcinoma, sarcopenia, immune checkpoint inhibitors, tyrosine kinase inhibitors, transarterial chemoembolization

Tianhao Cong,1 Chao Yang,1 Qi Cao,2 Jinrui Ren,1 Yingen Luo,1 Pei Yuan,2 Bo Zheng,2 Yu Liu,1 Hongcai Yang,1 Wendi Kang,1 Aixin Ou,1 Xiao Li1 1Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Xiao Li, Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Tel +86-13910309111, Fax +86-028-88092354, Email simonlixiao@gmail.comPurpose: Transarterial chemoembolization (TACE) represents a significant therapeutic modality for hepatocellular carcinoma (HCC). We aimed to develop a gene signature to accurately predict patient TACE response and explore the underlying mechanisms.Methods: Three independent datasets were utilized, including GSE104580, GSE14520 and external validation from the Cancer Hospital Chinese Academy of Medical Sciences. GSE104580 was randomly partitioned into a training set and a validation set, whereas GSE14520 was categorized into a resection group and a TACE group. Logistic regression was used to develop a TACE effectiveness model. Immunohistochemistry is utilized to confirm the protein expression trends of the signature genes. Immune infiltration and functional enrichment analyses were conducted to investigate the potential underlying mechanisms.Results: A 2-gene signature consisting of glycine N-methyltransferase (GNMT) and matrix metalloproteinase-12 (MMP12) was constructed, and based on this, all the patients were assigned TACE effectiveness scores and categorized into high effectiveness (HE) and low effectiveness (LE) groups. The HE group exhibited a better prognosis than the LE group in the various cohorts (p < 0.05). In the external validation set, immunohistochemistry confirmed the expression of the signature genes exhibiting an upregulated trend of GNMT in the HE group and MMP12 in the LE group, the LE group also exhibited a poorer prognosis [for overall survival (OS), HE group: 881 days vs LE group: 273 days (p < 0.05), and for progression-free survival (PFS), HE group: 458 days vs LE group: 136 days (p < 0.05)]. Multivariate analysis in all the datasets identified LE status as an independent risk factor for OS, disease-free survival (DFS) and PFS. The infiltration level of M0 macrophages and activated mast cells in the LE group was significantly higher than in the HE group. The hypoxia signaling pathway and glycolysis pathway were significantly enriched in the LE group.Conclusion: The loss of GNMT and the overexpression of MMP12 may be critical factors influencing TACE efficacy.Keywords: hepatocellular carcinoma, transarterial chemoembolization, immune infiltration, mast cell, glucose metabolism, hypoxic microenvironment

Chunmei Yang,1,&ast; Xiaoling Che,1,&ast; Yu Zhang,2 Didi Gu,1 Guidong Dai,1 Jian Shu,1 Lu Yang1 1Department of Radiology, The Affiliated Hospital of Southwest Medical University, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan Province, People’s Republic of China; 2Department of Radiology, The First People’s Hospital of Yibin, Yibin, 644000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Shu; Lu Yang, Department of Radiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, People’s Republic of China, Tel +86 0830-18980253083 ; +86 0830-2504762, Email shujiannc@163.com; yanglu@swmu.edu.cnBackground: Development of versatile nanoplatform still remains a great challenge due to multistep synthesis and complicated compositions. Therefore, it is significant to develop a facile method to synthesize a nanocomposite to achieve multimodal imaging and even imaging-guided cancer therapeutics.Methods and Results: In our study, hyaluronic acid-functionalized iron (II) tungstate nanoparticles (HA-FeWO4 NPs) were successfully synthesized as a versatile nanoplatform by a facile one-pot hydrothermal procedure. The formed multifunctional HA-FeWO4 NPs were investigated via a series of characterization techniques, which demonstrated good biocompatibility, excellent dispersion, low cytotoxicity, active tumor-targeting ability and high photothermal efficiency. Furthermore, tumor was clearly visualized by HA-FeWO4 NPs with multimodal imaging of infrared thermal imaging, magnetic resonance imaging, computed tomography imaging in 4T1 tumor bearing mice. More importantly, HA-FeWO4 could achieve multimodal imaging-guided photothermal therapy of 4T1 tumors.Conclusion: The constructed HA-FeWO4 NPs have great potential as ideal nanotheranostic agents for multimodal imaging and even imaging-guided cancer theranostics in biological systems.Keywords: theranostics, multimodal imaging, photothermal therapy, diagnostic imaging, nanomedicine

Yuan-Yuan Song,1,&ast; Ling Xu,2,&ast; Dan Liu,3 Mei Feng,2 Cui Yang,2 Yan Jiang,4 Ying Wu2 1Department of Critical Care Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 4Department of Nursing/Evidence-Based Nursing Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Wu, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, No. 37, Guoxue Alley, Chengdu, Sichuan Province, People’s Republic of China, Email wuying0917@wchscu.cnPurpose: China lifted its strict zero-Covid approach on December 7, 2022. This study aimed to investigate depression and anxiety symptoms and their associations among Chinese residents after the change in public policy.Methods: A cross-sectional sample of 925 Chinese residents (726 females and 199 males) was recruited using convenience and snowball sampling approach between 16 and 25 December 2022. Participants completed online questionnaires on basic information, depression, anxiety, COVID-19 related perceptions, and protective behaviors change.Results: Mild and moderate-to-severe depression symptoms were reported by 35.6% and 19.1% of participants, respectively. Nearly 40% of participants reported mild anxiety and 18.7% reported moderate-to-severe anxiety. Results from multinomial logistic regression analysis indicated that male gender, younger age, the presence of chronic disease, poorer self-rated mental health status, perceived impact, and worry were risk factors for both depression and anxiety, while higher education and protective behaviors change were protective factors. Besides, living with or caring for children (4– 6 years), family members or other housemates currently with influenza-like symptoms, and perceived severity were also risk factors for depression.Conclusion: Our findings provided initial evidence that Chinese residents may face heightened depression and anxiety during the early stage after the policy was released. Furthermore, we identified some vulnerable populations in need of prioritizing mental health assistance and some potentially modifiable factors associated with depression and anxiety, which provides an important guide for developing timely and effective psychological interventions and preparing for future pandemics.Keywords: COVID-19, public policy, depression, anxiety, COVID-19 related perceptions, protective behaviors change

Xiaodong Wang,1,2,&ast; Uet Yu,2,&ast; Chao Ding,2,3 Huiying Ye,2 Chunjing Wang,2 Chunlan Yang,2 Yue Li,2 Xiaohui Zhou,2 Qian Zhang,2 Sixi Liu,2 Feiqiu Wen1,2 1Department of Pediatrics, First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2Department of Hematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 3Discipline of Pediatrics, China Medical University, Shenyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feiqiu Wen, Department of Pediatrics, First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China, Email fwen62@163.com Sixi Liu, Department of Hematology and Oncology, Shenzhen Children’s Hospital, 7019 Yitian Road, Futian, Shenzhen, 518038, People’s Republic of China, Email tiger647@126.comBackground: The COVID-19 pandemic presents challenges for healthcare systems globally, especially in vulnerable populations such as pediatric hematopoietic stem cell transplant (HSCT) recipients. This study examines the clinical characteristics and outcomes of COVID-19 infection in pediatric HSCT recipients within one year post-HSCT.Methods: Retrospective analysis was conducted on data from 247 pediatric patients. None of them had received SARS-CoV-2 vaccination or had prior infection. SARS-CoV-2 infection was confirmed using RT-PCR testing. COVID-19 disease severity was categorized according to established guidelines. Demographic, clinical, laboratory, imaging and treatment data were collected.Results: The median age of the cohort was 7± 3.7 years, with thalassemia major as the predominant underlying disease. Allogeneic HSCT was performed in the majority of cases, with haploidentical donors being the most common source of grafts. Nearly half of the patients developed COVID-19, with significantly higher infection rates observed in recipients over 100 days compared to recipients within 100 days post-HSCT (40.1% vs 21.7%, p< 0.05, Fisher’s Exact test). Fever (n=107, 43.2%) and cough (n=88, 35.6%) were the most common symptoms. While most patients had mild disease and did not require specific anti-viral treatment, a significant proportion required hospitalization (n=34, 13.8%). Various treatments were employed hospitalized patients, including Paxlovid (n=19, 55.9%), methylprednisolone (n=7, 20.6%), IL-6 antibody (n=2, 5.9%), mesenchymal stem cells (n=3, 8.8%), and exosomes nebulization therapy (n=2, 5.9%). Despite multidisciplinary approaches, one patient died from severe respiratory failure. However, overall survival of all patients remained high (99.53%; CI 96.72– 99.93%), indicating favorable outcomes in pediatric HSCT recipients with COVID-19.Conclusion: This study provides insights into clinical features, therapeutic measures, and outcomes of pediatric HSCT recipients following COVID-19 infection in a large HSCT center in China. These findings contribute to our understanding of COVID-19 in this population and inform strategies to mitigate the impact the pandemic’s impact on their care.Keywords: COVID-19, SARS-CoV2, hematopoietic stem cell transplantation, pediatrics

Chenkai Yang,1,&ast; Xiangqian Cao,1,&ast; Lei He,2,3,&ast; Cong Wu,2,&ast; Mengxin Zhao,2 Fei Duan,2 Zhiwen Qiu,2 Xiaodong Zhu,2 Yilin Yan,1 Shengzhou Li,1 Wei Li,2 Bing Shen1 1Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Nanomedicine & Shanghai Key Laboratory of Cell Engineering, Naval Medical University, Shanghai, People’s Republic of China; 3School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li, Department of Nanomedicine & Shanghai Key Laboratory of Cell Engineering, Naval Medical University, 800 Xiangyin Road, Yangpu District, Shanghai, 200433, People’s Republic of China, Tel +86 21 81871644, Fax +86 21 81870801, Email liwei_dds@163.com Bing Shen, Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 85 Wujin Road, Hongkou District, Shanghai, 200080, People’s Republic of China, Tel/Fax +86 18017181979, Email urodrshenbing@shsmu.edu.cnIntroduction: Insufficient tumor permeability and inadequate nanoparticle retention continue to be significant limitations in the efficacy of anti-tumor drug therapy. Numerous studies have focused on enhancing tumor perfusion by improvement of tumor-induced endothelial leakage, often known as the enhanced permeability and retention (EPR) effect. However, these approaches have produced suboptimal therapeutic outcomes and have been associated with significant side effects. Therefore, in this study, we prepared tumor cell membrane-coated gold nanorods (GNR@TM) to enhance drug delivery in tumors through homogeneous targeting of tumor cell membranes and in situ real-time photo-controlled therapy.Methods: Here, we fabricated GNR@TM, and characterized it using various techniques including Ultraviolet-Visible (UV-Vis) spectrophotometer, particle size analysis, potential measurement, and transmission electron microscopy (TEM). The cellular uptake and cytotoxicity of GNR@TM were analyzed by flow cytometry, confocal laser scanning microscopy (CLSM), TEM, CCK8 assay and live/dead staining. Tissue drug distribution was determined by inductively coupled plasma mass spectrometry (ICP-MS) and immunofluorescence staining. Furthermore, to evaluate the therapeutic effect, mice bearing MB49 tumors were intravenously administered with GNR@TM. Subsequently, near-infrared (NIR) laser therapy was performed, and the mice’s tumor growth and body weight were monitored.Results: The tumor cell membrane coating endowed GNR@TM with extended circulation time in vivo and homotypic targeting to tumor, thereby enhancing the accumulation of GNR@TM within tumors. Upon 780 nm laser, GNR@TM exhibited excellent photothermal conversion capability, leading to increased tumor vascular leakage. This magnification of the EPR effect induced by NIR laser further increased the accumulation of GNR@TM at the tumor site, demonstrating strong antitumor effects in vivo.Conclusion: In this study, we successfully developed a NIR-triggered nanomedicine that increased drug accumulation in tumor through photo-controlled therapy and homotypic targeting of the tumor cell membrane. GNR@TM has been demonstrated effective suppression of tumor growth, excellent biocompatibility, and significant potential for clinical applications. Keywords: intratumor drug accumulation, photo-controlled therapy, homotypic targeting, tumor cell membrane, gold nanorods

Identifying biomarkers in non-small cell lung cancer (NSCLC) can improve diagnosis and patient stratification. We evaluated plasmas and sera for interleukins (IL)-11, IL-6, IL-8, IL-17A, and IL-33 as biomarkers in primary NSCLC patients undergoing surgical treatment against normal volunteers. Exhaled-breath condensates (EBCs), a potential source without invasive procedures, were explored in normal individuals. Due to separate recruitment criteria and intrinsic cohort differences, the NSCLC and control cohorts were not well matched for age (median age: 65 vs. 40 years; p < 0.0001) and smoking status (p = 0.0058). Interleukins were first assessed through conventional ELISA. IL-11 was elevated in NSCLC plasma compared to controls (49.71 ± 16.90 vs. 27.67 ± 14.06 pg/mL, respectively, p < 0.0001) but undetectable in sera and EBCs by conventional ELISA. Therefore, high-sensitivity PCR-based IL-11 ELISA was repeated, albeit with concentration discrepancies. IL11 gene and protein upregulation by RT-qPCR and immunohistochemistry, respectively, were validated in NSCLC tumors. The lack of detection sensitivity across IL-6, IL-8, IL-17A, and IL-33 suggests the need for further, precise assays. Surprisingly, biomarker concentrations can be dissimilar across paired plasmas and sera. Our results identified a need to optimize detection limits for biomarker detection and caution against over-reliance on just one form of blood sample for biomarker assessment.

Jing Zhou, Chunsong Yang, Qichen Xv, Liyun Wang, Liangjun Shen, Qingwei Lv Department of Neurosurgery, Shengzhou People’s Hospital (the First Affiliated Hospital of Zhejiang University Shengzhou Branch), Shengzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Chunsong Yang, Department of Neurosurgery, Shengzhou People’s Hospital (the First Affiliated Hospital of Zhejiang University Shengzhou Branch), Shengzhou, Zhejiang, People’s Republic of China, Email ycs821005@163.comBackground: Translocator protein (TSPO) is a biomarker of neuroinflammation and brain injury. This study aimed to ascertain the potential of serum TSPO as a predictor of cognitive impairment after acute intracerebral hemorrhage (ICH).Methods: In this prospective observational cohort study, 276 patients with supratentorial ICH were randomly assigned to two groups (184 patients in the study group and 92 in the validation group) in a 2:1 ratio. Serum TSPO levels were gauged at admission, and cognitive status was assessed using the Montreal Cognitive Assessment Scale (MoCA) post-stroke 3 months. A MoCA score of < 26 was considered indicative of cognitive impairment.Results: Serum TSPO levels were inversely correlated with MoCA scores (ρ=− 0.592; P< 0.001). Multivariate linear regression analysis showed that serum TSPO levels were independently associated with MoCA scores (β, − 0.934; 95% confidence interval (CI), − 1.412--0.455; VIF, 1.473; P< 0.001). Serum TSPO levels were substantially higher in patients with cognitive impairment than in the remaining patients (median, 2.7 versus 1.6 ng/mL; P< 0.001). Serum TSPO levels were linearly correlated with the risk of cognitive impairment under a restricted cubic spline (P=0.325) and independently predicted cognitive impairment (odds ratio, 1.589; 95% CI, 1.139– 2.216; P=0.016). Subgroup analysis showed that the relationship between serum TSPO levels and cognitive impairment was not markedly influenced by other parameters, such as age, sex, drinking, smoking, hypertension, diabetes mellitus, body mass index, and dyslipidemia (all P for interaction > 0.05). The model, which contained serum TSPO, National Institutes of Health Stroke Scale scores and hematoma volume, performed well under the receiver operating characteristic curve, calibration curve and decision curve, and using the Hosmer–Lemeshow test. This model was validated in the validation group.Conclusion: Serum TSPO level upon admission after ICH was independently associated with cognitive impairment, substantializing serum TSPO as a reliable predictor of post-ICH cognitive impairment.Keywords: translocator protein, intracerebral hemorrhage, cognitive impairment, biomarkers

Dongmei Guo,1 Yue Huang,2 Kun Wang,2 Chenguang Yang,2 Lili Ma,2 Yu Zhang,2 Haiyang Yu,2 Manhua Cui,1 Zhaohui Tang2 1Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin Province, 130041, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of ChinaCorrespondence: Manhua Cui, Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, 218 Ziqiang Road, Changchun, Jilin Province, 130041, People’s Republic of China, Email cuimanhua@126.com Yue Huang, Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of China, Tel/Fax +86 431 85262116, Email huangyue@ciac.ac.cnPurpose: Cervical cancer (CC) is a highly vascularized tumor with abundant abnormal blood vessel, which could be targeted by therapeutic strategies. Poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) have shown great potential as nano vascular disrupting agents (VDAs) in the realm of synergistic cancer therapy.Methods: In this study, we investigated the nanocharacteristics of CB-NPs, focusing on active pharmaceutical ingredients (API), as well as lyophilized samples combining API with protective agents (PAs). The in vivo efficacy of final sample (API + PAs) was evaluated.Results: The assembled sphere of API with complex core and thin-shell structure was confirmed. PAs were found to significantly influence in vivo efficacy. Collaborative efforts between API and PAs, namely mannitol and lactose, resulted in the most promising lyophilized sample, ie, the final sample (FS2) for CC therapy. Impressively, FS2 demonstrated an exceptional 100% cure rate on the CC U14-bearing mice model.Conclusion: FS2 has provided significant insights for cervical cancer therapy. It is also crucial to develop a comprehensive evaluation strategy for the formulation of nanomedicine, which has the potential to serve as a guideline for future clinical trials. Keywords: combretastatin A4, BLZ945, glutamic acid, nano character, cervical cancer

Junjie Chen,1,&ast; Xiwen Liao,1,2 Yining Wu,1,&ast; Shenjian Ou,1 Wei Qin,1 Chengkun Yang,1,2 Yufeng Tan,1 Quan Lao,1 Minhao Peng,1 Tao Peng,1,2 Xinping Ye1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China; 2Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, Nanning, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinping Ye; Tao Peng, Tel +86-771-5356528, Fax +86-771-5350031, Email yexinping@gxmu.edu.cn; pengtaogmu@163.comAbstract: Hepatocellular carcinoma (HCC) recurrence, which encompasses both true recurrence resulting from cancer spread and de novo tumors developing within the same cancer-prone liver, presents a complication in approximately 70% of cases within a 5-year timeframe. The efficacy of neoadjuvant therapy for recurrence after hepatectomy for hepatocellular carcinoma is still unclear. We report a case of recurrent massive advanced hepatocellular carcinoma with pathological complete remission was treated by continuous hepatic arterial infusion chemotherapy (HAIC) and sequential transcatheter arterial embolization (TAE) combined with secondary operation. One month after resection, the patient recurred (massive type 141mm× 76mm). After 4 times of HAIC sequential TAE conversion therapy, the tumor shrank significantly (70mm× 29mm), alpha-fetoprotein(AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels decreased significantly, residual liver volume[left half liver accounted for 39.85% of standard liver volume(left half liver + right anterior lobe) accounted for 80.17% of standard liver volume] and Indocyanine green 15-minute retention(ICG R15 8.0%) complies with surgical requirement.The second operation was performed, and the tumor was completely resected after hepatic blood flow occlusion Requirement. The postoperative pathological results showed complete remission (PCR) of the tumor, and no recurrence was found during the follow-up of 16 months. In this case, HAIC sequential TAE conversion therapy has good short-term effect on patients with postoperative recurrence of hepatocellular carcinoma, tumor burden is significantly reduced, the second surgery pathology achieves complete remission, safety and tolerance, it is worthy of study and promotion.Keywords: hepatocellular carcinoma, recurrence after resection, two-stage hepatectomy, complete remission, sequential therapy

Yandan Zhou,1 Zhili Feng,2,3 Jie Wen,2,3 Chi Yang,2,3 Qiancheng Jing2,3 1Changsha Aier Eye Hospital, Aier Eye Hospital Group, Changsha, Hunan, People’s Republic of China; 2Department of Otolaryngology Head and Neck Surgery, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of China; 3Institute of Otolaryngology Head and Neck Surgery, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Qiancheng Jing, Department of Otolaryngology-Head and Neck Surgery, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of China, Email 2022050001@usc.edu.cnBackground: Allergic rhinitis (AR) is a common allergic disease, and SLIT has shown effectiveness as a treatment method. This study focuses on the evaluation of serum TAM receptor tyrosine kinases (TYRO3, AXL, and MER) levels as potential indicators of disease severity and predictive markers for sublingual immunotherapy (SLIT) responsiveness in AR patients.Methods: A total of 160 AR subjects, including 40 mild AR (MAR) and 120 moderate-severe AR (MSAR) patients, and 40 healthy controls (HC) were recruited. Serum concentrations of TYRO3, AXL, and MER were measured and their relationships with disease severity were examined. In the MSAR group, 102 patients underwent SLIT, and the early efficacy was evaluated. The correlations between the baseline serum concentrations of TYRO3, AXL, and MER and the early responsiveness of SLIT were analyzed.Results: Serum concentrations of TYRO3, AXL, and MER were significantly reduced in AR patients, particularly in those MSAR subjects. Correlation analysis results indicated that serum TYRO3 and MER levels were negatively correlated with the visual analog scale (VAS) and the total nasal symptom score (TNSS). After one year of follow-up, 80 AR patients completed the treatment and were divided into effective and ineffective groups. Serum baseline levels of TYRO3 and MER were found to be lower in the effective group compared to the ineffective group. Additionally, there was a significant increase in serum TYRO3 and MER levels compared to baseline levels. Receiver operating characteristic (ROC) analysis revealed that circulating TYRO3 and MER had potential values for reflecting AR severity and predicting early SLIT responsiveness.Conclusion: Serum TYRO3 and MER concentrations were decreased in AR patients and negatively associated with disease severity. Circulating TYRO3 and MER seem to be promising indicators for monitoring the efficacy of SLIT in AR patients.Keywords: allergic rhinitis, sublingual immunotherapy, TAM receptor tyrosine kinases, TYRO3, AXL, MER