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Ziyan Zhong,1,* Jian Liu,2,* Yan Luo,1 Mei Wu,1 Feng Qiu,1 Hongqing Zhao,1 Yang Liu,1 Yajing Wang,3 Hongping Long,2 Lei Zhao,4 Yuhong Wang,1 Yuanshan Han,2 Pan Meng1 1Science & Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 2The First Hospital, Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China; 3Office of Science & Technology, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 4School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuanshan Han, The First Hospital, Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China, Email 121983755@qq.com Pan Meng, Science & Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China, Email 004181@hnucm.edu.cnBackground: Depression, a leading cause of disability worldwide, is characterized by dysfunction of immature neurons, resulting in dysregulated calcium homeostasis and impaired structural plasticity. Jujuboside A (JuA), a biologically active compound derived from Semen Ziziphi Spinosae, has demonstrated anti-anxiety and anti-insomnia properties. Recent studies suggest that JuA may be a promising antidepressant, but its underlying mechanisms remain unclear.Methods: Sprague-Dawley rats were subjected to chronic unpredictable mild stress (CUMS) to induce a depression model. JuA (12.5 mg/kg, 25 mg/kg, 50 mg/kg) was administered orally for 4 weeks. Emotional and cognitive function were assessed. Monoamine neurotransmitter levels were measured using enzyme-linked immunosorbent assay (ELISA). The number of immature neurons and calcium homeostasis were evaluated by immunofluorescence. Western blotting and immunofluorescence were employed to detect the expression of Sonic hedgehog (Shh) signaling proteins. Additionally, lentiviral vector expressing Shh shRNA (LV-Shh-RNAi) were infused intracerebrally to investigate the role of Shh in JuA’s antidepressant effects.Results: JuA significantly ameliorated depressive-like behavior and cognitive dysfunction in CUMS rats, increased monoamine neurotransmitter levels in serum and hippocampal tissue, reduced the number of BrdU/DCX (bromodeoxyuridine/doublecortin)-positive immature neurons, and attenuated calcium ion (Ca2+) concentration and Ca2+/calmodulin-dependent protein kinase II (CaMKII) levels in immature neurons. JuA also markedly elevated synaptic density and prominence complexity, upregulated Shh, Gli family zinc finger 1 and 2 (Gli1/2), synaptophysin (Syn) and postsynaptic density protein-95 (PSD-95) expression in the ventral dentate gyrus (vDG). However, knockdown of Shh in the vDG counteracted JuA’s therapeutic effects.Conclusion: These findings collectively suggest that JuA improves depressive-like behavior in CUMS rats by modulating calcium homeostasis and synaptic structural plasticity in immature neurons through the Shh signaling pathway.Keywords: Jujuboside A, Sonic hedgehog, Immature neuron, Calcium homeostasis, Depression

Yongkang Zhang,* Jiarui Liu,* Yuzhen Wang, Yuan Zong, Kangli Yin, Fang Cao, Xinyu Liang, Yemin Cao Diagnosis and Treatment Center of Vascular Disease, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yemin Cao; Yongkang Zhang, Diagnosis and Treatment Center of Vascular Disease, Shanghai TCM-Integrated Hospital, No. 230 Baoding Road, Hongkou District, Shanghai, People’s Republic of China, Tel +8613361831119 ; +8613761921568, Email caoyemin@shutcm.edu.cn; zhangyongkang_tcm@163.comPurpose: Peripheral arterial disease (PAD) is a chronic ischemic disease caused by atherosclerosis of the lower extremities, with early clinical symptoms manifesting mainly as intermittent claudication. Current treatment of PAD is based on the control of cardiovascular risk factors. However, even vasoactive drugs are not ideal for improving ischemic symptoms in the lower limbs of PAD patients. Ruanjian Qingmai granules, derived from the classic formula of the late Professor Jiuyi Xi, a famous traditional Chinese medicine doctor in Shanghai, have good clinical efficacy in the treatment of the pattern of blood vessel stasis and obstruction of PAD and have been used by more than 600,000 PAD patients over the past three decades. This study aims to evaluate the efficacy and safety of Ruanjian Qingmai granules in patients with symptomatic PAD.Patients and methods: A prospective, center-randomized, double-blind, placebo-controlled clinical trial will be conducted at 9 grade A tertiary hospitals in Shanghai. It is anticipated that 250 patients with early symptomatic PAD will be recruited and randomized to the control and intervention groups (1:1 ratio of central randomization). Subjects will be treated with Ruanjian Qingmai granules or placebo at 6 g twice daily for 16 weeks. The primary efficacy indicators are the pain-free walking distance and maximum walking distance. The secondary efficacy indicators are the ankle-brachial index, walking impairment questionnaire, quality of life score, and Chinese medicine syndrome score.Conclusion: Positive results from this study will demonstrate the efficacy and safety of Ruanjian Qingmai granules in improving ischemic symptoms in patients with symptomatic PAD.Clinical Registration: This study has been registered with the Chinese Clinical Trials Registry (ChiCTR2200056109, Date: 02/01/2022, https://www.chictr.org.cn/showproj.html?proj=150982).Keywords: peripheral arterial disease, Ruanjian Qingmai granules, intermittent claudication, efficacy, randomized controlled trial, protocol

Xinyang Nie,1– 3,* Jian Liu,1,2,* Daohan Wang,1,2,* Chuan Li,1,2 Yuxin Teng,1,2 Zhufeng Li,1,2 Yangpu Jia,1,2 Peiyao Wang,1,2 Jingyu Deng,2,3 Weidong Li,1,2 Li Lu1,2 1Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Lu; Weidong Li, Department of General surgery, Tianjin Medical University General Hospital, 154, Anshan Road, Heping District, Tianjin, 300052, People’s Republic of China, Email luli_1989@126.com; tjmughgs_lwd@163.comBackground: Cisplatin (DDP) resistance in gastric cancer (GC) is likely to come from gastric cancer stem cells (GCSC). It is a new idea to study the mechanism of the DDP-resistance in GCSC from miRNA.Materials and Methods: CD44+ GCSCs and CD44- control cells were constructed based on the HGC27 gastric cancer cell line. DDP sensitivities in CD44+ and CD44- cells were detected via CCK-8 assay. The differential expression of miR-21-5p in these cell lines was detected by RT‒qPCR. The expression levels of downstream TGF-β 2, SMAD2 and SMAD3 were determined through RT‒PCR and Western blotting. A luciferase assay was used to detect the relationship between miR-21-5p and TGFB2, and the TCGA database, clinical data from our centre, and vivo experiment were used for validation. Finally, we knocked down miR-21-5p to detect changes in cisplatin resistance in GCSCs and to verify changes in the levels of downstream pathways in GCSCs.Results: CD44+ GCSCs induced cisplatin resistance compared with CD44- cells. miR-21-5p was highly expressed in GCSCs, and the TGF-β 2/SMAD pathway was also highly expressed. TGFB2 was proven to be a downstream target gene of miR-21-5p and had a positive relationship with it in phenotype. After knockdown of miR-21-5p, the TGF-β 2/SMAD pathway was also inhibited, and the resistance of GCSCs to cisplatin was specifically decreased.Conclusion: MiR-21-5p promotes cisplatin resistance in gastric cancer stem cells by regulating the TGF-β 2/SMAD signalling pathway.Keywords: miR-21-5p, cisplatin resistance, GCSCs, TGF-β 2 pathway

Jing He,1,&ast; Nan Lin,2,&ast; Ting Jin,2 Ming Lin,1 Zuowei Huang,1 Shuxian Li,1 Jinling Liu,1 Lin Su,1 Xian Ye,2 Lei Wu,1 Zhenghong Song,2 Hongzhen Xu,2 Zhimin Chen1 1Department of Pulmonology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of China; 2Nursing Department, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhimin Chen, Department of Pulmonology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, 310052, People’s Republic of China, Email zmchen@zju.edu.cn Hongzhen Xu, Master of nursing, Nursing Department, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, 310052, People’s Republic of China, Email 6184020@zju.edu.cnBackground: Allergic conditions, identified as a significant global health challenge, are profoundly influenced by indoor allergens, especially house dust mites (HDM). Yet the relationship between mite sensitized components and respiratory allergies and asthma control remains poorly understood.Methods: A cohort of 96 children, either with allergic rhinitis (AR) or rhinitis with asthma syndrome (ARAS), was assessed. Protein microarray technology was deployed to quantify sIgE responses to the allergenic components of Der p and Der f.Results: The study cohort comprised 18 AR and 78 ARAS patients; with 43 mild and 53 moderate-to-severe AR; with 28 uncontrolled, 21 partially controlled, and 29 well-controlled asthma. Sensitization prevalence for HDM components was highest with Der p (97.9%), Der f 2 (97.9%), Der p 2 (94.8%), Der f 1(94.8%), Der p 1 (93.8%), Der p 23 (57.3%). Notably, sIgE concentrations for Der f and Der f 2 were significantly greater in the ARAS compared to AR (P < 0.05). While sIgE levels varied between mild and moderate-to-severe AR, the differences were not statistically significant (P > 0.05). However, Der p 23 sIgE levels demonstrated a significant fluctuation across the asthma control strata (P < 0.05), with the well-controlled group exhibiting the lowest readings.Conclusion: The sIgE levels to HDM allergens were higher in ARAS group compared to AR group, especially Der f and Der f 2, indicating an association between sIgE reactivity and the diagnosis of asthma. Reduced Der p 23 sIgE levels were indicative of enhanced asthma control.Keywords: house dust mite, allergic rhinitis, asthma, molecular sensitization, children

Yuhao Wei,1 Renwei Li,1 Yusha Wang,1,2 Jiali Fu,3 Jifeng Liu,4,5 Xuelei Ma1 1Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, West China School of Pharmacy, Sichuan University, Chengdu, People’s Republic of China; 4Department of Otolaryngology Head and Neck Surgery/Deep Underground Space Medical Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 5State Key Laboratory of Intelligent Construction and Healthy Operation and Maintenance of Deep Underground Engineering, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Xuelei Ma; Jifeng Liu, Email drmaxuelei@gmail.com; liujifeng777@wchscu.cnAbstract: Immunotherapy is a promising cancer treatment because of its ability to sustainably enhance the natural immune response. However, the effects of multiple immunotherapies, including ICIs, are limited by resistance to these agents, immune-related adverse events, and a lack of reasonable therapeutic targets available at the right time and place. The tumor microenvironment (TME), which features tumor-associated macrophages (TAMs), plays a significant role in resistance owing to its hypoxic microenvironment and lack of blood vessels, resulting in cancer immune evasion. To enhance immunotherapy, photodynamic therapy (PDT) can increase innate and adaptive immune responses through immunogenic cell death (ICD) and improve the TME. Traditional photosensitizers (PSs) also include novel nanomedicines to precisely target tumor cells or TAMs. Here, we reviewed and summarized current strategies and possible influencing factors for nanomedicines for cancer photoimmunotherapy.Keywords: cancer, tumor-associated macrophages, photodynamic therapy, nanomedicines, immunotherapy

Shuping Song,1,&ast; Jieqiong Liu,2,3,&ast; Wei Su,1 Haitao Yu,4 Binbin Feng,1 Yinshan Wu,1 Feng Guo,1 Zhenwei Yu2 1Intensive Care Unit, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3Department of Pharmacy, The 903rd Hospital of PLA Joint Logistic Support Force, Hangzhou, People’s Republic of China; 4Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Guo; Zhenwei Yu, Email 3408003@zju.edu.cn; yzw_srrsh@zju.edu.cnBackground: Tigecycline is considered one of the last resorts for treating infections caused by multidrug-resistant bacteria. Continuous renal replacement therapy (CRRT) is widely used in critically ill patients, especially those with acute kidney injury or severe infections. However, pharmacokinetic data for tigecycline in patients receiving CRRT are limited.Methods: This was a single-center prospective clinical study with intensive sampling that included critically ill patients who received tigecycline and CRRT. A population pharmacokinetic (PPK) model was developed and evaluated by goodness-of-fit plots, bootstrap analysis, visual predictive checks, and numerical predictive checks. Pharmacokinetic/pharmacodynamic target attainment and cumulative fraction of response analyses were performed to explore the potential need for dose adjustments of tigecycline in CRRT.Results: In total, 21 patients with 167 concentrations were included. A two-compartment model adequately described the tigecycline concentration–time points, but no covariates were found to adequately explain the viability in the pharmacokinetic parameters of tigecycline. The typical values of CL, Q, V1 and V2 were 4.42 L/h, 34.8 L/h, 30.9 L and 98.7 L, respectively. For most infections, the standard regimen of 50 mg/12 h was deemed appropriate, expect for skin and soft skin tissue infections and community-acquired pneumonia caused by Acinetobacter baumannii and Klebsiella pneumoniae, which required a dosage regimen of 100 mg/12 h or higher.Conclusion: A tigecycline PPK model describing critically ill patients undergoing CRRT was successfully developed. The optimized dosage regimens for various infections are recommended.Keywords: tigecycline, population pharmacokinetics, critically ill, continuous renal replacement therapy

Xinchen Wang,1,&ast; Haiwei Bu,1,2,&ast; Chen Wei,1 Jingyi Liu,1– 3 Yuewen Qi,3,4 Weichao Shan,1– 3 Ying Zhang,1– 3 Lixian Sun1– 3 1Department of Cardiology, The Affiliated Hospital of Chengde Medical University, Chengde, People’s Republic of China; 2The Cardiovascular Research Institute of Chengde, Chengde, People’s Republic of China; 3Hebei Key Laboratory of Panvascular Diseases, Chengde, People’s Republic of China; 4Central Laboratory of The Affiliated Hospital of Chengde Medical University, Chengde, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lixian Sun, Department of Cardiology, The Affiliated Hospital of Chengde Medical University, Chengde, China, No. 36, Nanyingzi Street, Shuangqiao District, Chengde, Hebei Province, People’s Republic of China, Tel +86 0314 227 9016, Fax +86 0314 227 4895, Email lixiansun01@126.comPurpose: To elucidate the predictive values of adipocytokines in patients with acute coronary syndrome (ACS).Patients and Methods: Overall, 297 patients with ACS were consecutively enrolled in this prospective cohort study between June 2015 and July 2017 and completed follow-up with a median follow-up time of 6.5 years. For consistency, the last visit date was June 20, 2023. Serum levels of retinol-binding protein-4 (RBP4), interleukin-1β (IL-1β), monocyte chemoattractant protein 1(MCP-1), adrenomedullin (ADM), netrin 1 (NTN 1), and omentin were measured using enzyme-linked immunosorbent assay. Follow-up data were collected during clinical visits or through telephone interviews at 1, 3, 6, 12 months, and annually. The primary endpoint was defined as major adverse cardiovascular events (MACEs), including all-cause mortality, rehospitalization for percutaneous coronary intervention, and severe angina requiring rehospitalization.Results: All biomarkers displayed a good diagnostic ability of MACEs. The Kaplan–Meier curve showed that the cumulative survival rates of high level of RBP4, IL-1β, and MCP-1 and low level of the ADM, NTN1, and omentin had lower cumulative survival rates (Log rank tests: all p< 0.05). After adjustment in the Cox hazard proportional model, the results were RBP4 ≥ 6.87 ng/mL, hazard ratio (HR)=2.512, p=0.003; IL-1β≥ 58.95 pg/mL, HR=3.809, p< 0.001; MCP-1 ≥ 401.75 pg/mL, HR=4.047, p< 0.001; ADM≤ 120.01 ng/mL, HR=3.930, p=0.008; NTN1 ≤ 63.7 pg/mL, HR=3.345, p=0.007; omentin ≤ 4.54 ng/mL, HR=2.830, p=0.004. P-values for interaction were > 0.05 in the sex, age, and dyslipidemia subgroups.Conclusion: Pro-inflammation adipocytokines RBP4, IL-1β, and MCP-1 increased and anti-inflammation biomarkers ADM, NTN1, and omentin decreased were independently associated with a higher risk of MACEs in patients with ACS.Keywords: acute coronary syndrome, adipocytokines, prognosis

Wei Qiang,1,&ast; Mengyi Li,1,2,&ast; Sucai Song,1,3 Ruiqing Dong,1 Tongxin Zhang,1 Xuna Kou,1 Yuan Wu,1 Zhaoxu Wang,1,4 Jiayue Liu,1 Juan Liu,1 Yi Wang,1 Xiaoyan Wu,1 Bingyin Shi,1 Hui Guo1 1Department of Endocrinology and Metabolism, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Endocrinology, Xi’an People’s Hospital, Xi’an, Shaanxi, 710100, People’s Republic of China; 3Department of Endocrinology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 4Department of Endocrinology, Luohe Central Hospital, Luohe, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Guo, Department of Endocrinology and Metabolism, The First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Street, Xi’an, People’s Republic of China, Tel +86-13709292996, Fax +86-029-85323974, Email 13709292996@139.comIntroduction: The long-acting insulin analogue insulin degludec (IDeg) is increasingly recommended for type two diabetes (T2DM), yet clinical experience in China remains limited. This retrospective study aimed to delineate the initiation strategy for IDeg in Chinese hospitalized patients with T2DM.Methods: We retrospectively analyzed 217 Chinese hospitalized patients with T2DM who initiated IDeg from December 2018 to June 2020, calculating the initial dose and examining correlations between clinical characteristics and glucose profiles.Results: The initial IDeg doses ranged from 0.15 to 0.18 IU/kg·d, showing no association with clinical characteristics. During titration, mean blood glucose levels (MEAN) correlated positively with diabetes duration, age, and Glycosylated Hemoglobin (HbA1c), and negatively with body mass index (BMI), triglycerides (TG), and low-density lipoprotein (LDL). The coefficient of variation (CV) in glucose levels correlated positively with HbA1c and negatively with BMI and TG. The mean amplitude of glycemic excursions (MAGE) mirrored these trends, with additional negative correlations to estimated glomerular filtration rate (eGFR) and serum albumin (ALB). Notably, glycemic variability parameters did not correlate with the presence of diabetic ketoacidosis (DKA) at admission. Hypoglycemia was observed in 21 patients, with differences in MEAN and CV during titration being the only significant findings.Conclusion: The initial IDeg dosing was inadequate and not tailored to clinical features, and there were weak correlations between diabetes duration, age, BMI, eGFR, LDL, and ALB levels and glucose profile post-initiation.Keywords: T2DM, insulin degludec, glucose variability, insulin initiation

Jingjing Liu, Gaosheng Zhou, Zewen Tong, Xiaoting Wang, Dawei Liu Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Dawei Liu, Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, 1&num; Shuai Fu Yuan, Dong Cheng District, Beijing, 100730, People’s Republic of China, Tel +86-10-69152305, Email daweiliu05@163.comBackground: Metabolic changing is the significant host stress response during sepsis, but there is increasing evidence that uncontrolled metabolic reprogramming is a contributing factor to sepsis. Nevertheless, its association with outcome in patients with sepsis has been poorly investigated. As the key enzyme of metabolic reprogramming, the clinical value of PDK1 and LDH in patients with sepsis will be investigated in this study.Methods: We collected serum from 167 ICU patients within 24 hours of admission for a single-center prospective observational study. The levels of PDK1 and LDH were detected by enzyme-linked adsorption method. Pearson or Spearman coefficient for correlation analysis between PDK1, LDH and clinical indicators. Areas under the ROC curves for evaluation of mortality prediction. Kaplan–Meier survival curve analysis was performed, and Cox proportional hazards model was performed to determine the risk factors for 28-day mortality.Results: The PDK1/LDH in the septic shock group was statistically different between both the sepsis group and ICU control group, and had good correlation with ScvO2 and lactate. In predicting 28-day mortality in patients with sepsis, the best AUC was observed for PDK1/LDH, and was higher than the AUC for PDK1, lactate, and SOFA. Additionally, patients with lower PDK1/LDH had markerablely higher 28-day mortality. The multivariate Cox proportional hazards model revealed that PDK1/LDH < 0.1808 were the independent risk factors for 28-day mortality in sepsis.Conclusion: The level of PDK1/LDH at admission was markedly decreased in patients with septic shock, which can serve as a novel independent prognostic biomarker for predicting mortality.Keywords: sepsis, septic shock, PDK1/LDH, metabolic reprogramming, mortality

Yang Xu,1,&ast; Yue Wu,1,&ast; Jianhong Liu,2 Lili Xiao,1 Ying Zhang1 1Department of Gastroenterology, Daqing Oilfield General Hospital, Daqing, Heilongjiang, 163000, People’s Republic of China; 2Department of Breast and Thyroid Surgery, Daqing Oilfield General Hospital, Daqing, Heilongjiang, 163000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Zhang, Email zhangying750114@163.comBackground: The study explored the prognostic value of caudal-type homeobox transcription factor 2 (CDX2) in stage II and III gastric cancer.Methods: This study evaluated the expression level of CDX2 in gastric cancer in a hospital cohort (n=197) using immunohistochemistry. According to a semiquantitative score used to determine CDX2 expression, the cases were divided into a low CDX2 group (116 cases) and a high CDX2 group (81 cases). The RNA-seq expression data from 291 patients with stage II and III gastric cancer from The Cancer Genome Atlas (TCGA) cohort were used to verify the immunohistochemistry results. Based on the median CDX2 expression value, the TCGA patients were divided into a low CDX2 group (145 cases) and a high CDX2 group (146 cases). The relationships among CDX2 expression and clinicopathological features were determined using the Chi-square test. Cox proportional hazards regression models were applied to estimate the independent prognostic factors. The probability of survival was determined using the Kaplan-Meier method and Log rank tests.Results: Based on the Cox multivariate analysis, CDX2 was the independent prognostic factor in the hospital and TCGA cohorts. In the hospital cohort, CDX2 expression was associated with an improved DFS (hazard ratio [HR] = 0.4076, 95% CI, 0.2675– 0.6210, P = 0.0001) and OS (HR = 0.4183, 95% CI, 0.2744– 0.6375, P = 0.0002). In the TCGA cohort, CDX2 expression also was associated with an improved DFS (HR = 0.5948, 95% CI, 0.4153– 0.8521, P = 0.0054) and OS (HR = 0.5976, 95% CI, 0.4172– 0.8561, P = 0.0058). Furthermore, the CDX2 expression level was correlated with an improved DFS (P = 0.0025) and OS (P = 0.0015) using the Kaplan-Meier Plotter database for gastric cancer.Conclusion: CDX2 is a potential prognostic biomarker for stage II and III gastric cancer. In addition, CDX2 positive cancer patients are more likely to have resectable tumors and exhibit better survival rates.Keywords: gastric cancer, CDX2, immunoreactivity, chemotherapy, prognostic marker

Panpan Fan,1,&ast; Pan Fu,2,3,&ast; Jing Liu,1,&ast; Chuanqing Wang,2,3 Xiaolei Zhang,1 Yixue Wang,1 Yingying Zhang,1 Ting Zhu,1 Caiyan Zhang,1 Guoping Lu,1 Gangfeng Yan,1 Members and affiliations of China Paediatric Intensive care Unit Pathogen Surveillance Network (CHIPS)Panpan Fan,1 Pan Fu,2 Jing Liu,1 Xiaolei Zhang,1 Yixue Wang,1 Yingying Zhang,1 Ting Zhu,1 Caiyan Zhang,1 Chuanqing Wang,2 Guoping Lu,1 Gangfeng Yan,1 Hong Ren,3 Juanzhen Li,3 Yucai Zhang,4 Yiping Zhou,4 Chengmei Zhang,5 Zhenjie Chen,5 Mingming Zhou,5 Zhengjiang Bai,6 Saihu Hang,6 Lili Hang,6 Hehe Chen,7 Yao Zheng,7 Qunying Chen,7 Pengwei Zhu,8 Yong Li,8 Yan Xu,8 BiZhen Zhu,9 Huixuan Shi,9 Shaoxian Hong,10 Yukun Huang,10 Meilian Huang,10 Danqun Jing,11 Wenjia Tong,11 ChengYu Zhang,11 Weiguo Yang,12 Weike Mang,12 Qing meng,12 Yibing Cheng,13 Qunqun Zhang,13 Kaijie Gao,13 Huiming Xu,14 Yuxia Li,14 Hanghai Ding,14 Xiulan Lu,15 Jiaotian Huang,15 Jianlong Liu,15 Yourong Zhu,16 Yuanyuan Chen,16 Shufang Xiao,17 Juan He,17 Li Jiang,17 Jianli Chen,18 Yi Lin,18 Jia Lei18 1Department of Pediatric Intensive Care Unit, Children’s Hospital of Fudan University, National Center for Children’s Health, Shanghai, People’s Republic of China; 2Lab of Microbiology, Department of Clinical Laboratory, Children’s Hospital of Fudan University, National Center for Children’s Health, Shanghai, People’s Republic of China; 3Nosocomial Infection Control Department, Children’s Hospital of Fudan University, National Center for Children’s Health, Shanghai, People’s Republic of China; 1Department of Pediatric Intensive Care Unit, Children’s Hospital of Fudan University, National Center for Children’s Health, Shanghai, People’s Republic of China; 2Clinical Microbiology Laboratory, Department of Nosocomial Infection Control, Children’s Hospital of Fudan University, National Center for Children’s Health, Shanghai, People’s Republic of China; 3Department of Pediatric Intensive Care Unit, Shanghai Children’s Medical Center affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Pediatric Intensive Care Unit, Shanghai Children’s Hospital affiliated to Shanghai Jiaotong University, Shanghai, People’s Republic of China; 5Department of Pediatric Intensive Care Unit, Children’s Hospital Affiliated to Zhejiang University Medical School, Hangzhou, People’s Republic of China; 6Department of Pediatric Intensive Care Unit, Children’s Hospital of Soochow University, Suzhou, People’s Republic of China; 7Department of Pediatric Intensive Care Unit, Ningbo Women and Children’s Hospital, Ningbo, People’s Republic of China; 8Department of Pediatric Intensive Care Unit, Wuxi Children’s Hospital, Wuxi, People’s Republic of China; 9Department of Pediatric Intensive Care Unit, The First Affiliated Hospital of Xiamen University, Xiamen, People’s Republic of China; 10Department of Pediatric Intensive Care Unit, Xiamen Children’s Hospital, Xiamen, People’s Republic of China; 11Department of Pediatric Intensive Care Unit, Anhui Children’s Hospital, Hefei, People’s Republic of China; 12Department of Pediatric Intensive Care Unit, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 13Department of Pediatric Intensive Care Unit, Henan Children’s Hospital, Zhengzhou, People’s Republic of China; 14Department of Pediatric Intensive Care Unit, Kaifeng Children’s Hospital, Kaifeng, People’s Republic of China; 15Department of Pediatric Intensive Care Unit, Hunan Children’s Hospital, Changsha, People’s Republic of China; 16Department of Pediatric Intensive Care Unit, Jiangxi Provincial Children’s Hospital, Nanchang, Kunming, People’s Republic of China; 17Department of Pediatric Intensive Care Unit, Kunming Children’s Hospital, People’s Republic of China; 18Department of Pediatric Intensive Care Unit, Guiyang Children’s Hospital, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoping Lu; Gangfeng Yan, Email 13788904150@163.com; gangfeng_yan@fudan.edu.cnObjective: To investigate the characteristics and drug resistance patterns of Klebsiella pneumoniae (K. pneumoniae) infection in pediatric intensive care unit (PICU).Methods: K. pneumoniae strains from 17 domestic PICUs were analyzed for overall condition and drug resistance using WHO-NET software.Results: From 2016 to 2022, there was a linear increase in the detection rate of K. pneumoniae (P< 0.05), with a total of 2591 (9.7%) strains detected. The primary sites of K. pneumoniae detection were the respiratory tract (71.1%), blood (8.6%), and urinary tract (7.1%). K. pneumoniae’s resistance to penicillin drugs exceeded 90%, and are over 50% to cephalosporins. Resistance to cefoperazone-sulbactam decreased from 51.7% to 25.7%, and ranged from 9.1% to 20.8% for ceftolozane-tazobactam. Carbapenem-resistant K. pneumoniae strains constituted 32.3%. Resistance to imipenem and meropenem have decreased to 33.8% and 40.2%, while increased to 35.2% for ertapenem. Levofloxacin and amikacin resistance rates have decreased to 25.7% and 9.1%, but remain high at 63.8% for moxifloxacin and 44.6% for ciprofloxacin. K. pneumoniae demonstrated the lowest resistance rates to polymyxin B (0.9%), tigecycline (2.2%), and polymyxin E (3.1%). No strain of K. pneumoniae was resistant to both polymyxin B and meropenem. However, some strains showed co-resistance to meropenem with other antibiotics, including tigecycline (2%), imipenem (16%), amikacin (27%), colistin (37%), and levofloxacin (41%).Conclusion: The rates of isolation and drug resistance of K. pneumoniae in PICU have significantly increased over 7 years. Careful antibiotic use, infection control strategies, and appropriate antibiotic combinations are crucial in addressing this problem.Keywords: pediatric intensive care unit, Klebsiella pneumoniae, bacterial drug resistance

Jiale Xu,&ast; Musen Xu,&ast; Xin Gao, Jiahang Liu, Jingchao Sun, Ruiqi Ling, Xuchen Zhao, Xifeng Fu, Shaojian Mo, Yanzhang Tian Department of Biliary and Pancreatic Surgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanzhang Tian, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, No. 99, Longcheng Street, Xiaodian District, Taiyuan, Shanxi Province, People’s Republic of China, Phone/Fax +86-13903512030, Email tyz2030@163.comObjective: To analyze the influence of diabetes mellitus on the clinical outcomes of moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP).Methods: This retrospective study included patients diagnosed with MSAP and SAP at Shanxi Bethune Hospital from January 1, 2017, to December 31, 2021. Clinical data were collected, including patient demographics, 24-hour laboratory indicators, and inflammation indices. Propensity score matching (PSM) was used to compare outcomes before and after matching. Patients were randomized into training and validation sets (7:3) to develop and validate a clinical prediction model for infected pancreatic necrosis (IPN).Results: Among 421 patients, 79 had diabetes at admission. Before PSM, diabetic patients had higher incidences of peripancreatic fluid (71% vs 47%, p< 0.001) and IPN (48% vs 10%, p< 0.001), higher surgical intervention rates (24% vs 12%, p=0.008), and significant differences in abdominocentesis (22% vs 11%, p=0.014). After PSM, 174 patients were matched, and the diabetes group still showed higher incidences of peripancreatic fluid (69% vs 47%, p=0.008), IPN (48% vs 11%, p< 0.001), and surgical intervention rates (27% vs 13%, p=0.037). Diabetes, modified CT severity index (MCTSI), serum calcium, and HDL-c were identified as independent risk factors for IPN. The prediction model demonstrated good predictive value.Conclusion: In MSAP and SAP patients, diabetes mellitus can exert an influence on their clinical outcome and is an independent risk factor for IPN. The alignment diagram and web calculator constructed on the basis of diabetes mellitus, modified CT severity index (MCTSI), serum calcium and high-density lipoprotein cholesterol (HDL-c) have good predictive value and clinical guidance for the occurrence of IPN in MSAP and SAP.Keywords: acute pancreatitis, diabetes, propensity score matching, predictive model

Mengyi Shen,1,&ast; Leyu Zhou,1,&ast; Xiaoli Fan,1 Ruiqi Wu,1 Shuyun Liu,2 Qiaoyu Deng,1 Yanyi Zheng,1 Jingping Liu,2 Li Yang1 1Department of Gastroenterology and Hepatology and Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2NHC Key Laboratory of Transplant Engineering and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Yang; Jingping Liu, Email yangli_hx@scu.edu.cn; liujingping@scu.edu.cnBackground: Autoimmune hepatitis (AIH) is a serious liver disease characterized by immune disorders, particularly effector T-cell overactivation. This study aimed to explore the therapeutic effect and underlying mechanism of mesenchymal stem cell-derived extracellular vesicle (MSC-EV) treatment on CD4+ T-cell overactivation and liver injury in AIH.Methods: The metabolic changes of CD4+ T cells were assayed in human AIH and mouse hepatitis models. The liver protective effect of MSC-EVs was evaluated by transaminase levels, liver histopathology and inflammation. The effect of MSC-EVs on the metabolic state of CD4+ T cells was also explored.Results: Enhanced glycolysis (eg, ~1.5-fold increase in hexokinase 2 levels) was detected in the CD4+ T cells of AIH patient samples and mouse hepatitis models, whereas the inhibition of glycolysis decreased CD4+ T-cell activation (~1.8-fold decrease in CD69 levels) and AIH liver injury (~6-fold decrease in aminotransferase levels). MSC-EV treatment reduced CD4+ T-cell activation (~1.5-fold decrease in CD69 levels) and cytokine release (~5-fold decrease in IFN-γ levels) by reducing glycolysis (~3-fold decrease) while enhancing mitochondrial oxidative phosphorylation (~2-fold increase in maximal respiration) in such cells. The degree of liver damage in AIH mice was ameliorated after MSC-EV treatment (~5-fold decrease in aminotransferase levels). MSC-EVs carried abundant mitochondrial proteins and might transfer them to metabolically reprogram CD4+ T cells, whereas disrupting mitochondrial transfer impaired the therapeutic potency of MSC-EVs in activated CD4+ T cells.Conclusion: Disordered glucose metabolism promotes CD4+ T-cell activation and associated inflammatory liver injury in AIH models, which can be reversed by MSC-EV therapy, and this effect is at least partially dependent on EV-mediated mitochondrial protein transfer between cells. This study highlights that MSC-EV therapy may represent a new avenue for treating autoimmune diseases such as AIH.Keywords: autoimmune hepatitis, extracellular vesicles, metabolic reprogramming, mitochondria, inflammation

Yun Zhu,1,&ast; Lingyan Li,2,&ast; Wenxiao Wang,3,&ast; Xiaodan Liu,1 Meng Xue Zhang,1 Xiumin Chen,4 Xiaofeng Hou,5 Weimei Wang,6 Tuo Min,7 Jinmei Liu,8 Lecui Liu,9 Chengjun Liu,10 Zhong Jiang,11 Yanping Wang,12 Dayun Chang,13 Hua Pan1 1Department of Pediatric Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 2Department of Pediatrics, Zibo Maternal and Child Health Hospital, Zibo, Shandong, People’s Republic of China; 3Department of Pediatrics, Yantai Yuhuangding Hospital, Yantai, Shandong, People’s Republic of China; 4Department of Pediatrics, Qingzhou People’s Hospital, Weifang, Shandong, People’s Republic of China; 5Department of Pediatrics, Laizhou City People’s Hospital, Laizhou, Shandong, People’s Republic of China; 6Department of Pediatrics, Haiyang People’s Hospital, Haiyang, Shandong, People’s Republic of China; 7Department of Pediatrics, Jining First People’s Hospital, Jining, Shandong, People’s Republic of China; 8Department of Pediatrics, West Coast New District Hospital of Chinese Medicine, Huangdao, Shandong, People’s Republic of China; 9Department of Neonatology, People’s Hospital of Wulian, Wulian, Shandong, People’s Republic of China; 10Department of Pediatrics, Linyi Central Hospital, Linyi, Shandong, People’s Republic of China; 11Department of Pediatrics, Rehabilitation University Qingdao Central Hospital, Qingdao, Shandong, People’s Republic of China; 12Department of Pediatrics, Qingdao Traditional Chinese Medicine Hospital, Qingdao, Shandong, People’s Republic of China; 13Department of Pediatrics, Weihai Municipal Hospital, Weihai, Shangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Pan, Department of Pediatric Intensive Care Unit, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, Shandong, 266003, People’s Republic of China, Tel +8618366205226, Email panhua1881@163.comIntroduction: The Omicron variant is the present predominant COVID-19 strain worldwide. Accurate mortality prediction can facilitate risk stratification and targeted therapies. The study aimed to evaluate the feasibility of the difference in hematocrit and albumin (HCT-ALB) levels, alone or combined with the pediatric Sequential Organ Failure Assessment (pSOFA) score and lactate level, to predict the in-hospital mortality of COVID-19 Omicron variant-infected pediatric patients.Methods: A multicenter retrospective cohort study was performed for children with COVID-19 Omicron variant infection between December 2021 and January 2022. The demographics, clinical characteristics, hospital admission laboratory test results, and treatments were recorded. The in-hospital mortality was documented. The associations between HCT-ALB levels and mortality, and between HCT-ALB+pSOFA+lactate and mortality were analyzed.Results: A total of 119 children were included. The median age was 1.6 (interquartile range: 0.5– 6.2) years old. There were 70 boys and 49 girls. The mortality rate was 14.3% (17/119). The univariate and multivariate Cox regression analysis revealed that HCT-ALB was associated to in-hospital mortality (hazard ratio: 1.500, 95% confidence interval: 1.235– 1.822, p< 0.001). The receiver operating characteristic curve analysis revealed that HCT-ALB can be used to accurately predict in-hospital mortality at a cut-off value of − 0.7 (area under the curve: 0.888, sensitivity: 0.882, specificity: 0.225, Youden index: 0.657, p< 0.001). These patients were assigned into three groups based on the HCT-ALB level, pSOFA score, and lactate level (low-, medium-, and high-risk groups). The Kaplan-Meier analysis revealed that the mortality increased in the high-risk group, when compared to the medium-risk group (p< 0.01). The latter group had a higher mortality, when compared to the low-risk group (p< 0.01).Conclusion: The HCT-ALB level can be applied to predict the in-hospital mortality of children infected with the COVID-19 Omicron variant. Its combination with other variables can improve prediction performance.Keywords: COVID-19, omicron variant, hematocrit, albumin, mortality

Wenlu Li,1,2,&ast; Yaolin Gong,1,2,&ast; Jing Zhang,1,2 Jiong Liu,1,2 Jiali Li,1,2 Shaozhi Fu,3 Wen Xiu Ren,1,2 Jian Shu1,2 1Department of Radiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Xiu Ren; Jian Shu, Department of Radiology, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping St, Jiangyang District, Luzhou, Sichuan, 646000, People’s Republic of China, Email xrenwenxiux@swmu.edu.cn; shujiannc@swmu.edu.cnIntroduction: Targeting, imaging, and treating tumors represent major clinical challenges. Developing effective theranostic agents to address these issues is an urgent need.Methods: We introduce an “all-in-one” tumor-targeted theranostic platform using CuFeSe2-based composite nanoparticles (CuFeSe2@PA) for magnetic resonance (MR) and computed tomography (CT) dual model imaging-guided hyperthermia tumor ablation. Plerixafor (AMD3100) is bonded to the surface of CuFeSe2 as a targeting unit. Due to the robust interaction between AMD3100 and the overexpressed Chemokine CXC type receptor 4 (CXCR4) on the membrane of 4T1 cancer cells, CuFeSe2@PA specifically recognizes 4T1 cancer cells, enriching the tumor region.Results: CuFeSe2@PA serves as a contrast agent for T2-weighted MR imaging (relaxivity value of 1.61 mM− 1 s− 1) and CT imaging. Moreover, it effectively suppresses tumor growth through photothermal therapy (PTT) owing to its high photothermal conversion capability and stability, with minimized side effects demonstrated both in vitro and in vivo.Discussion: CuFeSe2@PA nanoparticles show potential as dual-mode imaging contrast agents for MR and CT and provide an effective means of tumor treatment through photothermal therapy. The surface modification with Plerixafor enhances the targeting ability of the nanoparticles, performing more significant efficacy and biocompatibility in the 4T1 cancer cell model. The study demonstrates that CuFeSe2@PA is a promising multifunctional theranostic platform with clinical application potential. Keywords: tumor targeting, photothermal therapy, dual model imaging, theranostic platform, chemokine cxc type receptor 4

Chang-Sheng Ma,1,2,&ast; Ya-Ping Ma,1,3,&ast; Bo Han,1,2,&ast; Wan-Li Duan,1 Shu-Chen Meng,1 Min Bai,1 Hao Dong,1 Li-Ying Zhang,1 Meng-Yuan Duan,1,2 Jing Liu,1 Ai-Jun Deng,2 Mao-Tao He1,2 1Department of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Ophthalmology, Affiliated Hospital of Shandong Second Medical University, Weifang, People’s Republic of China; 3Department of Pathology, The 942Hospital of the People’s Liberation Army Joint Logistic Support Force, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mao-Tao He, Department of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China, Tel +86-18209617186, Fax +86-0536-3081201, Email hemaotao@sdsmu.edu.cn Ai-Jun Deng, Department of Ophthalmology, Affiliated Hospital of Shandong Second Medical University, Weifang, People’s Republic of China, Email dengaijun@hotmail.comPurpose: Ischemic stroke is a refractory disease wherein the reperfusion injury caused by sudden restoration of blood supply is the main cause of increased mortality and disability. However, current therapeutic strategies for the inflammatory response induced by cerebral ischemia-reperfusion (I/R) injury are unsatisfactory. This study aimed to develop a functional nanoparticle (MM/ANPs) comprising apelin-13 (APNs) encapsulated in macrophage membranes (MM) modified with distearoyl phosphatidylethanolamine-polyethylene glycol-RVG29 (DSPE-PEG-RVG29) to achieve targeted therapy against ischemic stroke.Methods: MM were extracted from RAW264.7. PLGA was dissolved in dichloromethane, while Apelin-13 was dissolved in water, and CY5.5 was dissolved in dichloromethane. The precipitate was washed twice with ultrapure water and then resuspended in 10 mL to obtain an aqueous solution of PLGA nanoparticles. Subsequently, the cell membrane was evenly dispersed homogeneously and mixed with PLGA-COOH at a mass ratio of 1:1 for the hybrid ultrasound. DSPE-PEG-RVG29 was added and incubated for 1 h to obtain MM/ANPs.Results: In this study, we developed a functional nanoparticle delivery system (MM/ANPs) that utilizes macrophage membranes coated with DSPE-PEG-RVG29 peptide to efficiently deliver Apelin-13 to inflammatory areas using ischemic stroke therapy. MM/ANPs effectively cross the blood-brain barrier and selectively accumulate in ischemic and inflamed areas. In a mouse I/R injury model, these nanoparticles significantly improved neurological scores and reduced infarct volume. Apelin-13 is gradually released from the MM/ANPs, inhibiting NLRP3 inflammasome assembly by enhancing sirtuin 3 (SIRT3) activity, which suppresses the inflammatory response and pyroptosis. The positive regulation of SIRT3 further inhibits the NLRP3-mediated inflammation, showing the clinical potential of these nanoparticles for ischemic stroke treatment. The biocompatibility and safety of MM/ANPs were confirmed through in vitro cytotoxicity tests, blood-brain barrier permeability tests, biosafety evaluations, and blood compatibility studies.Conclusion: MM/ANPs offer a highly promising approach to achieve ischemic stroke-targeted therapy inhibiting NLRP3 inflammasome-mediated pyroptosis. Keywords: apelin-13, cerebral ischemia-reperfusion injury, macrophage membrane, ischemic stroke therapy, pyroptosis

Lu Xu,1,&ast; Jing Liu,2,&ast; Suli Li,1 Xingchen Lu,1 Wenjie Gu,1 Shunhua Zhu,1 Meng Wang,1 Xiaojin Wu,3 Qingli Huang1 1Public Experimental Research Center of Xuzhou Medical University, Xuzhou, Jiangsu Province, 221004, People’s Republic of China; 2Department of Neurology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou No. 1 People’s Hospital, Xuzhou, Jiangsu Province, 221100, People’s Republic of China; 3Department of radiotherapy, the affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou No. 1 People’s Hospital, Xuzhou, Jiangsu Province, 221100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaojin Wu; Qingli Huang, Email xiaojinwu@xzhmu.edu.cn; qlhuang@xzhmu.edu.cnPurpose: Developing novel multimodal nanomaterials-based anticancer agents to meet complex clinical demands is an urgent challenge. This study presents a novel uniform hollow S-doped NiCuFe Prussian blue analogue (NiCuFe-S) with satisfactory size and properties as anticancer agents for efficient cervical cancer therapy using a simple and environmentally friendly procedure.Methods: The formation mechanism and the reason for enhanced performance of NiCuFe-S were characterized and discussed by diverse spectroscopic and microscopic methods. Moreover, to demonstrate the anti-cancer ability of NiCuFe-S, in vitro and in vivo experiments were carried out.Results: Compared to the non-doped NiCuFe, the NiCuFe-S exhibited significantly enhanced photothermal and catalytic activity attributed to the electronic bandgap-narrowing effect and the increased electron circuit paths resulting from S doping. The hollow structure of NiCuFe-S facilitated the loading of small-molecule drugs, such as doxorubicin (DOX), transforming it into a multimodal nanoplatform for cervical cancer treatment. In vitro and in vivo experiments proved the potential of the NiCuFe-S nanotheranostic agent for chemodynamic therapy (CDT), photothermal therapy (PTT), and chemotherapy for cervical cancer.Conclusion: This research not only overcomes inherent limitations but also significantly broadens the applications of Prussian blue analogues in biomedicine.Keywords: nanomaterials, Prussian blue analogue, catalytic, photothermal therapy, anticancer

Siyuan Chen,1,2 Jia Liu,1,2 Zhili Feng,1,2 Liubo Zhou,1,2 Yuexiang Cai,1,2 Qiancheng Jing1,2 1Department 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; 2Institute 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: Exosomes carry various types of transcripts and serve as promising biomarkers for inflammatory diseases. However, the role of serum exosomal microRNAs (miRNAs) in chronic rhinosinusitis with nasal polyps (CRSwNP) is poorly clarified.Methods: A prospective exploratory cohort of 10 CRSwNP patients was conducted, and the serum exosome samples were subjected to miRNA sequencing. Two independent prospective cohorts, consisting of 40 and 54 patients respectively, were recruited from different medical centers for validation. These cohorts were monitored for over two years, with postoperative recurrence serving as the primary outcome measure. The top 3 differentially exosomal miRNAs were validated in the serum samples, and their predictive values for recurrence were assessed.Results: Eight CRSwNP patients completed the follow-up, comprising 4 non-recurrent cases and 4 recurrent cases. Distinctive profiles of serum exosomal miRNAs were identified between the two groups. In the first validation cohort, reverse transcription-polymerase chain reaction results indicated elevated serum exosomal miR-3174 and miR-6750-5p expressions, along with reduced miR-192-3p levels in the recurrence group compared to the non-recurrence group. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival analysis demonstrated significant correlations between expressions of exosomal miR-3174 and miR-192-3p and the risk of postoperative recurrence. These findings were further validated in the second cohort, confirming the elevation of both miRNAs in the recurrence group and their associations with recurrence risk. Additionally, serum exosomal miR-3174 levels increased in recurrent cases compared to their baseline levels.Conclusion: Circulating exosomal microRNA signatures may influence the risk of postoperative recurrence in CRSwNP patients. Serum exosomal elevated exosomal miR-3174 and decreased miR-192-3p were correlated with CRSwNP recurrence risk.Keywords: exosome, chronic rhinosinusitis with nasal polyps, biomarker, recurrence

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

Wenguang Lai,1,&ast; Xiaoli Zhao,2,&ast; Zhiyong Gao,1 Haozhang Huang,3,4 Donghui Huang,1 Yang Zhou,3,4 Guoxiao Liang,3,4 Shiqun Chen,3,4 Jin Liu,3 Yong Liu3 1Department of Pharmacy, Heyuan People’s Hospital; Guangdong Provincial People’s Hospital, Heyuan Hospital, Heyuan, 517001, People’s Republic of China; 2Department of Cardiology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 3Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Liu; Jin Liu, Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China, Tel +86 02083827812-10528, Fax +86 02083851483, Email liuyong@gdph.org.cn; ljaw397017568@163.comPurpose: Heart failure with preserved ejection fraction (HFpEF) is inherently a complex inflammatory syndrome, and heightened inflammation is strongly associated with an increased risk of death. However, the association of systemic inflammation levels with total and cardiovascular death among patients with HFpEF remains unknown. We aimed to investigate the prognostic impact of systemic inflammation on all-cause and cardiovascular death among patients with HFpEF.Patients and Methods: Patients with HFpEF were included in this study. Systemic inflammation response index (SIRI) is defined as the multiplication of neutrophil and monocyte divided by lymphocyte count, and patients were divided into four groups based on SIRI quartiles. Cox regression models and competing risk models were used to examine the relationships between SIRI and total and cardiovascular‑specific mortality, respectively.Results: 9,986 patients with HFpEF were included in five tertiary hospitals. During a median follow-up period of 4.4 years, a total of 2004 patients died, of which 965 were cardiovascular deaths. After fully adjusting for confounders, elevated SIRI level was significantly related to the increased risk of all-cause death (Q2, Q3, Q4: adjusted hazard ratio (aHR) [95 confidence interval (CI)%] =1.17[1.01– 1.35], 1.31[1.13– 1.52], 1.51[1.30– 1.76], respectively; P for trend < 0.001). The elevated quartile of SIRI showed higher risks of cardiovascular death, but there was no statistically significant increased risk of cardiovascular death across the lower SIRI quartile (model 3: Q2, Q3, Q4: aHR [95CI%] =1.22[0.99– 1.51], 1.50[1.20– 1.86], 1.73[1.37– 2.18], respectively; P for trend < 0.001).Conclusion: Elevated systemic inflammation level on admission was correlated with an increased risk of all-cause and cardiovascular death among patients with HFpEF. The SIRI may serve as a promising marker of risk stratification for patients with HFpEF.Keywords: heart failure with preserved ejection fraction, systemic inflammatory response index, all-cause death, cardiovascular death

Jia Liu, Fan Zhang Department of Geriatrics, Peking University Third Hospital, Beijing, People’s Republic of ChinaCorrespondence: Fan Zhang, Department of Geriatrics, Peking University Third Hospital, 49 North Garden Road, Beijing, 100191, People’s Republic of China, Email zhangfan_puh3@yeah.netBackground: Emerging evidence suggests a link between muscle health and the autonomic nervous system, but research is scarce. This study examines the connection between long-term heart rate variability (HRV) measured autonomic function and sarcopenia in the elderly, focusing on muscle mass and strength.Patients and Methods: This retrospective cross-sectional study comprised 132 elderly hospitalized patients. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria, involving reduced muscle mass and strength. HRV was assessed using standard deviation of NN intervals (SDNN), with values below 100 milliseconds indicating reduced HRV. Multivariate logistic regression and Pearson’s correlation analyses were conducted to explore the associations between sarcopenia, muscle metrics, and HRV parameters.Results: Among elderly hospitalized patients, 45.45% had reduced HRV, with sarcopenia patients showing a fivefold higher risk (OR: 5.042; p = 0.034). Grip strength and SARC-CalF scores were independent factors associated with reduced HRV. Moderate correlations were noted between grip strength and HRV indices, particularly with SDNN (r = 0.393, p = 0.001) and the triangular index (r = 0.385, p < 0.001), while a weaker correlation was found with very low frequency power (VLF) (r = 0.283, p = 0.006). No significant correlations were identified between HRV and muscle mass. Regression analyses revealed significant independent associations between HRV parameters and the decline in muscle strength and the onset of sarcopenia.Conclusion: Reduced HRV is closely linked to sarcopenia and diminished muscle strength in the elderly, with the triangular index and SDNN as key indicators, highlighting HRV’s potential in muscle health assessment.Keywords: muscle strength, SDNN, triangular index, muscle mass

Ling Duan,1 Wenhui Guo,1 Shuo Yin,1 Shoubo Yang,1 Jie Liu,2 Yunyun Duan,3 Gehong Dong,4 Wenbin Li,1 Feng Chen1 1Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 2Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 3Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 4Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of ChinaCorrespondence: Wenbin Li; Feng Chen, Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, No. 119 West Nansihuan Road, Beijing, 100070, People’s Republic of China, Tel +86-10-59975034, Email liwenbin@ccmu.edu.cn; chenfeng406@sina.comPurpose: To investigate the prognostic significance of pan-immune-inflammation value (PIV) and PILE score (based on PIV, lactate dehydrogenase (LDH), and Eastern Cooperative Oncology Group Performance Status (ECOG PS)) in patients with primary central nervous system lymphoma (PCNSL).Patients and Methods: A total of 109 patients were enrolled. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The PILE score was incorporated based on PIV, LDH levels, and ECOG PS. The Kaplan–Meier curves and Cox hazards regression models were applied for survival analyses. The relationship between PIV, PILE, and therapeutic response was examined.Results: Baseline high PIV was significantly associated with worse overall survival (OS) in univariate (HR 3.990, 95% CI 1.778– 8.954, p < 0.001) and multivariate (HR 3.047, 95% CI 1.175– 7.897, p = 0.022) analyses. High PIV was also associated with worse progression-free survival (PFS) in univariate (HR 2.121, 95% CI 1.075– 4.186, p = 0.030) but not significant in multivariate analyses. PIV outperformed other systemic inflammation parameters. The patients in the high PILE group (PILE score 2– 3) had worse OS (p = 0.008) and PFS (p < 0.001) compared to the low PILE group (PILE score 0– 1). PILE was independently associated with therapeutic response to initial treatment (OR 0.17, 95% CI 0.05– 0.46; p < 0.001).Conclusion: High PIV and PILE were correlated with worse clinical outcomes in PCNSL patients, indicating that PIV and PILE might be a powerful predictor of prognosis and a potential predictive indicator for therapeutic response in PCNSL.Keywords: primary central nervous system lymphoma, pan-immune inflammation value, PILE score, prognosis

Ming Wei,1 Xi Chen,1 Jun Liu,1 Tianmeng Li,1 Peng Wang,1 Shuai Wang,1 Jing Wang,2,3 Li Gu1 1Department of Infectious Diseases and Clinical Microbiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Jing Wang, Beijing Anding Hospital, Capital Medical University, 5 Ankang Hutong Road, Xicheng District, Beijing, 100088, People’s Republic of China, Email kycwangjing@mail.ccmu.edu.cn Li Gu, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, People’s Republic of China, Email didcm2006@mail.ccmu.edu.cnPurpose: Carbapenem-resistant Enterobacterales (CRE) infection is an urgent threat to human health. This study aimed to develop and validate a novel multiplex real-time PCR (multi-qPCR) assay for the detection of the blaKPC, blaNDM, blaIMP, blaOXA-48-like, and blaVIM genes in CRE isolates and clinical samples, as well as to compare it with three phenotypic methods.Methods: The reliability and limit of detection (LOD) of the multi-qPCR assay were evaluated. PCR and DNA sequencing were used as the reference methods to identify carbapenemase genes in CRE isolates and clinical samples. The accuracy of the multi-qPCR assay, modified carbapenem inactivation and EDTA-modified carbapenem inactivation method (mCIMandeCIM), carbapenemase inhibitor-based combined disk test (CDT), and colloidal gold-based immunochromatographic test was compared with the reference methods with 182 isolates of CRE. Furthermore, 112 clinical samples were collected to validate the efficacy of this multi-qPCR assay.Results: The standard deviations (CVs) of intra-assay and inter-assay of the multi-qPCR assay were ≤ 0.53% and ≤ 2.04% for detecting the five major carbapenemase genes, respectively; while the LOD ranged from 2× 102 copies/mL to 8× 102 copies/mL. PCR and DNA sequencing confirmed 168 out of 182 CRE isolates producing carbapenemase(s): KPC (n = 93), NDM (n = 46), IMP (n = 8), OXA-48-like (n = 14), VIM (n = 1), KPC&NDM (n = 5), and KPC&NDM&IMP (n = 1). The accuracy of mCIMandeCIM, CDT, Colloidal Gold, and the multi-qPCR assay was 96.2%, 89.6%, 100%, and 100% respectively for detecting carbapenemase(s) producers. Moreover, the sensitivity and specificity of the multi-qPCR assay were all 100% for the detection of each carbapenemase gene in clinical samples, compared with PCR and sequencing.Conclusion: For clinical isolate detection, the multi-qPCR assay is comparable to Colloidal Gold, and superior to mCIMandeCIM and CDT; while for clinical samples detection, it also shows excellent performance. Therefore, the multi-qPCR assay has great potential for clinical diagnosis.Keywords: carbapenem-resistant Enterobacterales, carbapenemases detection, multiplex real-time PCR assay, mCIM/eCIM, combined disk test, immunochromatographic test

Jing Liu, Ping Yang, Meng Hu Department of Hematology, First Affiliated Hospital of Henan University of Science and Technology, Henan, 471000, People’s Republic of ChinaCorrespondence: Meng Hu, Department of Hematology, First Affiliated Hospital of Henan University of Science and Technology, Henan, 471000, People’s Republic of China, Email 3259294525@qq.comAbstract: In this report, the patient was a 57-year-old woman who had been diagnosed with aplastic anemia for 3 years. This patient underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Twenty-four months after allo-HSCT, the patient experienced cognitive dysfunction, memory loss, and involuntary movements. Various central nervous system (CNS) complications may occur after allo-HSCT, which can lead to severe clinical problems. Diagnosis is often difficult because of the absence of distinctive clinical symptoms. In addition, different neurological disorders may show similar symptoms. Although antibodies in the CSF or serum have become well recognized in several CNS disorders, cases of autoimmune CNS disorders after allo-HSCT have rarely been reported. Here, we report the case of a patient who developed encephalitis associated with antibodies against glial fibrillary acidic protein (GFAP) after allo-HSCT. To the best of our knowledge, this is the first report of the involvement of antibodies against GFAP in post-transplantation encephalitis. Of course, all processes met the ethical and patient consents were obtained.Keywords: glial fibrillary acidic protein, autoimmune encephalitis, allo-HSCT

Xiangdong Gongye,1,2,&ast; Peng Xia,1,2,&ast; Tianyin Ma,1,2,&ast; Yibo Chai,1,2 Zhang Chen,1,2 Yimin Zhu,1,2 Chengming Qu,1,2 Jie Liu,1,2 Wing Wa Guo,1,2 Minghe Zhang,1,2 Yingyi Liu,1,2 Ming Tian,1,2 Yufeng Yuan1– 3 1Department of Hepatobiliary & Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Hubei, People’s Republic of China; 3Taikang Center for Life and Medical Sciences of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming Tian; Yufeng Yuan, Email dr.med.mingtian@whu.edu.cn; yuanyf1971@whu.edu.cnBackground: The liver’s regenerative capacity allows it to repair itself after injury. Extracellular vesicles and particles (EVPs) in the liver’s interstitial space are crucial for signal transduction, metabolism, and immune regulation. Understanding the role and mechanism of liver-derived EVPs in regeneration is significant, particularly after partial hepatectomy, where the mechanisms remain unclear.Methods: A 70% hepatectomy model was established in mice, and EVPs were isolated and characterized using electron microscopy, nanocharacterization, and Western blot analysis. Combined metabolomic and transcriptomic analyses revealed β-sitosterol enrichment in EVPs and activation of the Hedgehog signaling pathway during regeneration. The role of β-sitosterol in EVPs on the Hedgehog pathway and its targets were identified using qRT-PCR, Western blot analysis. The regulation of carnitine synthesis by this pathway was determined using a dual luciferase assay. The effect of a β-sitosterol diet on liver regeneration was verified in mice.Results: After 70% hepatectomy, the liver successfully regenerated without liver failure or death. At 24 hours post-surgery, tissue staining showed transient regeneration-associated steatosis (TRAS), with increased Ki67 positivity at 48 hours. EVPs displayed a spherical lipid bilayer structure with particle sizes of 70– 130 nm. CD9, CD63, and CD81 in liver-derived EVPs were confirmed. Transcriptomic and metabolomic analyses showed EVPs supplementation significantly promoted carnitine synthesis and fatty acid oxidation. Tissue staining confirmed accelerated TRAS resolution and enhanced liver regeneration with EVP supplementation. Mass spectrometry identified β-sitosterol in EVPs, which binds to Smo protein, activating the Hedgehog pathway. This led to the nuclear transport of Gli3, stimulating Setd5 transcription and inducing carnitine synthesis, thereby accelerating fatty acid oxidation. Mice with increased β-sitosterol intake showed faster TRAS resolution and liver regeneration compared to controls.Conclusion: Liver-derived EVPs promote regeneration after partial hepatectomy. β-sitosterol from EVPs accelerates fatty acid oxidation and promotes liver regeneration by activating Hedgehog signaling pathway. Keywords: liver regeneration, extracellular vesicles and particles, β-sitosterol, carnitine synthesis, hedgehog signaling pathway

Ting Sun,1,2,&ast; Jingfang Liu,3,&ast; Hui Wang,3,&ast; Bing Xiang Yang,3– 5 Zhongchun Liu,3 Jie Liu,6 Zhiying Wan,3 Yinglin Li,1 Xiangying Xie,1 Xiaofen Li,3 Xuan Gong,3 Zhongxiang Cai1 1Department of Nursing, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Health Science Center, Yangtze University, Jingzhou, People’s Republic of China; 3Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 4School of Nursing, Wuhan University, Wuhan, People’s Republic of China; 5Population and Health Research Center, Wuhan University, Wuhan, People’s Republic of China; 6Anesthesiology, Virginia Commonwealth University Health System, Richmond, VA, USA&ast;These authors contributed equally to this workCorrespondence: Zhongxiang Cai, Department of Nursing, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, Hubei Province, 430060, People’s Republic of China, Email tg20201228@163.com Xuan Gong, Department of Psychiatry, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, Hubei Province, 430060, People’s Republic of China, Email 12048387@qq.comBackground: Non-suicidal self-injury (NSSI) is a significant social issue, especially among adolescents with major depressive disorder (MDD). This study aimed to construct a risk prediction model using machine learning (ML) algorithms, such as XGBoost and random forest, to identify interventions for healthcare professionals working with adolescents with MDD.Methods: This study investigated 488 adolescents with MDD. Adolescents was randomly divided into 75% training set and 25% test set to testify the predictive value of risk prediction model. The prediction model was constructed using XGBoost and random forest algorithms. We evaluated the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, recall, F Score of the two models for comparing the performance of the two models.Results: There were 161 (33.00%) participants having NSSI. Compared without NSSI, there were statistically significant differences in gender (P=0.035), age (P=0.036), depressive symptoms (P=0.042), sleep quality (P=0.030), dysfunctional attitudes (P=0.048), childhood trauma (P=0.046), interpersonal problems (P=0.047), psychoticism (P) (P=0.049), neuroticism (N) (P=0.044), punishing and Severe (F2) (P=0.045) and Overly-intervening and Protecting (M2) (P=0.047) with NSSI. The AUC values for random forest and XGBoost were 0.780 and 0.807, respectively. The top five most important risk predictors identified by both machine learning methods were dysfunctional attitude, childhood trauma, depressive symptoms, F2 and M2.Conclusion: The study demonstrates the suitability of prediction models for predicting NSSI behavior in Chinese adolescents with MDD based on ML. This model improves the assessment of NSSI in adolescents with MDD by health care professionals working. This provides a foundation for focused prevention and interventions by health care professionals working with these adolescents.Keywords: non-suicidal self-injury, adolescents, major depressive disorder, risk prediction model

Hui Huang,1– 3,&ast; Qing Ye,1– 4,&ast; Yulan Xu,1– 3,&ast; Baoming Tao,1– 3 Junlan Liu,1– 3 Tian Xie,1– 3 Lingfeng Zha1– 3 1Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4School of Nursing, Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tian Xie; Lingfeng Zha, Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People’s Republic of China, Tel +86-15972150162 ; +86-15827177185, Email xietian@hust.edu.cn; zhalf@hust.edu.cnPurpose: We investigated the risk factors and characteristic clinical features of peripartum cardiomyopathy (PPCM) to lay the groundwork for early identification, screening, diagnosis, and intervention in high-risk pregnant women.Patients and methods: A retrospective case-control study was conducted to analyze data from 44 patients with PPCM and 226 normal pregnant women from a Chinese population.Results: Significant differences were found between the groups in terms of various factors such as age, body mass index (BMI), heart rate, and medical history. Logistic regression models identified abnormal electrocardiography (OR=18.852), upper respiratory tract infection (OR=41.822), gestational hypertension (OR=18.188), and cesarean section (OR=8.394) as risk factors for PPCM. Common clinical features observed in patients with PPCM included cough, wheezing, and chest tightness (68.18%), left heart enlargement (56.82%) and valvular insufficiency (81.82%). Additionally, cardiotropic virus was detected in a subset of patients (43.18%) and NT-proBNP was elevated ≥ 400 pg/mL (81.82%).Conclusion: In the Chinese population, the presence of abnormal electrocardiograms during pregnancy, history of upper respiratory tract infection, gestational hypertension, and maternal choice of cesarean section suggest the possibility of PPCM development. Factors such as advanced age, family history of cardiovascular disease, gestational diabetes mellitus, eclampsia, anemia, and hypoproteinemia should be considered. Clinically, patients present with cough, wheezing, chest tightness, enlarged left heart, valvular insufficiency and NT-proBNP elevated ≥ 400 pg/mL. This study could serve as a valuable reference for medical practitioners for the early identification and screening of patients with PPCM.Keywords: peripartum cardiomyopathy, risk factors, clinical features, early identification

Yong-Yao Wu,1,&ast; Jun-Yuan Li,1,&ast; Qiao-Jing Xia,1 Yi-Yi Gao,1 Chao Zhang,1 Peng-Jie Xu,1 Jiang Liu,1 Hao-Jie Zhang,1 Ri-Zhen Yu2 1Department of Nephrology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang Province, 315099, People’s Republic of China; 2Urology & Nephrology Center, Department of Nephrology, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang Province, 310014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao-Jie Zhang, Department of Nephrology, Ningbo Medical Center Lihuili Hospital, No. 1111 Jiangnan Road, Yinzhou District, Ningbo City, Zhejiang Province, 315099, People’s Republic of China, Email zhang_haojie843@outlook.com Ri-Zhen Yu, Urology & Nephrology Center, Department of Nephrology, Affiliated People’s Hospital, Hangzhou Medical College, No. 158 Shangtang Road, Gongshu District, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86 571-85893889, Fax +86 571-85131448, Email rizhen_3180yu83@126.comObjective: Sarcopenia is more common in maintenance hemodialysis (MHD) patients, and the aim of this study is to analyze the risk factors associated with sarcopenia in MHD patients, along with its correlation to emotional status and quality of life.Methods: This is a cross-sectional cohort study. A total of 111 MHD patients who were treated in the Department of Nephrology of our hospital were selected as the study subjects by convenience sampling. The quality of life and emotional status were evaluated by health survey scale (SF-36), self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Regression analysis was used to explore the influencing factors of sarcopenia. Correlation analysis was used to investigate the correlation between sarcopenia and quality of life and emotional status.Results: The prevalence of sarcopenia was 59.8%. The results showed that age, gender, body mass index (BMI), dialysis time, economic status, marital status and pre-dialysis creatinine were significant factors affecting the development of sarcopenia in hemodialysis patients (p< 0.05). The SF-36 total score was significantly lower in the sarcopenia group (72.05± 12.28 vs 78.03± 10.55) than in the non-sarcopenia group, but the anxiety scale score (52.97± 4.67 vs 36.2± 3.36) and depression scale score (57.67± 4.58 vs 38.71± 3.77) were significantly higher than those in the non-sarcopenia group (p< 0.001). Correlation analysis showed that sarcopenia was positively correlated with SAS and SDS scores and negatively correlated with SF-36 total score (p < 0.05).Conclusion: The risk of sarcopenia was higher among MHD patients who were older, male, single, with a longer MHD duration, lower economic status, lower BMI, comorbid diabetes and lower levels of creatinine.Keywords: maintenance hemodialysis, sarcopenia, quality of life, risk factors, cross-sectional studies

Holly Mansell,1 Nicola Rosaasen,2 Jenny Wichart,3 Patricia West-Thielke,4 David Blackburn,1 Juxin Liu,5 Rahul Mainra,6 Ahmed Shoker,6 Brianna Groot,7 Kevin Wen,8 Anita Wong,9 Bita Bateni,10 Cindy Luo,11 Paraag Trivedi12 1College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada; 2Saskatchewan Transplant Program, Saskatchewan Health Authority, Saskatoon, SK, Canada; 3Department of Pharmacy, Alberta Health Services, Calgary, AB, Canada; 4University of Illinois Health Sciences System, Chicago, IL, USA; 5Department of Mathematics and Statistics, College of Arts and Science, University of Saskatchewan, Saskatoon, SK, Canada; 6Saskatchewan Transplant Program; Department of Medicine, University of Saskatchewan, Saskatoon, SK, Canada; 7Canadian Hub for Applied and Social Research, University of Saskatchewan, Saskatoon, SK, Canada; 8Division of Nephrology and Transplant Immunology, Department of Medicine University of Alberta, Edmonton, AB, Canada; 9Department of Pharmacy, University of Alberta Hospital, Edmonton, AB, Canada; 10St. Paul’s Hospital, and University of British Columbia, Vancouver, BC, Canada; 11Vancouver General Hospital; Faculty of Pharmaceutical Sciences, the University of British Columbia, Vancouver, BC, Canada; 12Transplant Recipient/Patient Advisor, Regina, SK, CanadaCorrespondence: Holly Mansell, College of Pharmacy and Nutrition, Health Sciences Building (E3208), 107 Wiggins Road, Saskatoon, SK, S7N 5E5, Canada, Email holly.mansell@usask.caAbstract: Sub-optimal adherence to immunosuppressant medications reduces graft survival for kidney transplant recipients and adherence-enhancing interventions are resource and time intensive. We performed a multi-center randomized controlled trial to investigate the impact of an electronically delivered intervention on adherence. Of 203 adult kidney transplant recipients who received a de novo kidney transplant n = 173 agreed to participate (intent-to-treat population) and were randomized to the intervention (video education plus behavior contract n = 91) or the control (standard education, n = 82). No significant differences were found between the groups for medication adherence measured by the Basel Assessment of Adherence to Immunosuppressive Medications Scale, intrapatient variability in tacrolimus levels, time in therapeutic range for any immunosuppressant, knowledge, self-efficacy, QOL, or hospitalizations. Among a subgroup of 64 participants randomized to the intervention group who completed a post-intervention questionnaire, two-thirds (67%, n = 43) reported watching at least 80% of the videos and 58% (n = 37) completed the electronic goal setting exercise and adherence contract. An autonomous goal setting exercise and electronic behavioural contract added to standard of care did not improve any outcomes. Our findings reiterate that nonadherence in transplantation is a difficult multifactorial problem that simple solutions will not solve. Trial registration number NCT03540121.Keywords: kidney transplant, solid organ transplant, medication adherence, immunosuppression

Xun Zhou,1,2,&ast; Jingzhou Liu,2,&ast; Shuang Xiao,2,3,&ast; Xiaoqing Liang,1,2 Yi Li,2 Fengzhen Mo,3 Xin Xin,2 Yang Yang,2 Chunsheng Gao1,2 1School of Pharmacy, Henan University, Kaifeng, People’s Republic of China; 2State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, People’s Republic of China; 3School of Pharmacy, Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengzhen Mo; Xin Xin, Email mofzhen@163.com; 13511014091@163.comAbstract: Gene therapy aims to add, replace or turn off genes to help treat disease. To date, the US Food and Drug Administration (FDA) has approved 14 gene therapy products. With the increasing interest in gene therapy, feasible gene delivery vectors are necessary for inserting new genes into cells. There are different kinds of gene delivery vectors including viral vectors like lentivirus, adenovirus, retrovirus, adeno-associated virus et al, and non-viral vectors like naked DNA, lipid vectors, polymer nanoparticles, exosomes et al, with viruses being the most commonly used. Among them, the most concerned vector is adeno-associated virus (AAV) because of its safety, natural ability to efficiently deliver gene into cells and sustained transgene expression in multiple tissues. In addition, the AAV genome can be engineered to generate recombinant AAV (rAAV) containing transgene sequences of interest and has been proven to be a safe gene vector. Recently, rAAV vectors have been approved for the treatment of various rare diseases. Despite these approvals, some major limitations of rAAV remain, namely nonspecific tissue targeting and host immune response. Additional problems include neutralizing antibodies that block transgene delivery, a finite transgene packaging capacity, high viral titer used for per dose and high cost. To deal with these challenges, several techniques have been developed. Based on differences in engineering methods, this review proposes three strategies: gene engineering-based capsid modification (capsid modification), capsid surface tethering through chemical conjugation (surface tethering), and other formulations loaded with AAV (virus load). In addition, the major advantages and limitations encountered in rAAV engineering strategies are summarized.Keywords: AAV engineering, capsid modification, surface tethering, virus load, rational design, directed evolution, machine learning

Mingming Chen,1 Shuting Chang,1 Yunpeng Xu,1 Hong Guo,2 Jian Liu1,3 1The First Clinical Medical College of Lanzhou University, Lanzhou City, Gansu Province, People’s Republic of China; 2Department of Critical Care Medicine, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou City, Gansu Province, People’s Republic of China; 3Gansu Provincial Maternity and Child-Care Hospital (Gansu Provincial Center Hospital), Lanzhou City, Gansu Province, People’s Republic of ChinaCorrespondence: Jian Liu, Department of Clinical Medicine, The First Clinical Medical College of Lanzhou University, No. 1, Donggang West Road, Chengguan District, Lanzhou City, Gansu Province, People’s Republic of China, Tel +86 136 0935 4197, Email medecinliujian@163.comAbstract: Chronic Obstructive Pulmonary Disease (COPD) exerts a severe toll on human health and the economy, with high prevalence and mortality rates. The search for bioactive components effective in the treatment of COPD has become a focal point of research. Beetroot juice, readily accessible and cost-effective, is noted for its ability to enhance athletic performance and for its preventive and therapeutic impact on hypertension. Beetroot juice is a rich source of dietary nitrates and modulates physiological processes via the nitrate-nitrite- nitric oxide pathway, exerting multiple beneficial effects such as antihypertensive, bronchodilatory, anti-inflammatory, antioxidant, hypoglycemic, and lipid-lowering actions. This paper provides a review of the existing research on the effects of beetroot juice on COPD, summarizing its potential in enhancing exercise capacity, lowering blood pressure, improving vascular function, and ameliorating sleep quality among patients with COPD. The review serves as a reference for the prospective use of beetroot juice in the symptomatic improvement of COPD, as well as in the prevention of exacerbations and associated comorbidities.Keywords: chronic obstructive pulmonary disease, beetroot, nitrates, nitric oxide, exercise, vascular function

Yuru He,1,2 Xing Wang,1,2 Zuowei Wang,3,4 Ping Zhang,5 Xiaojia Huang,3,4 Meihong Yu,5 Jill K Murphy,6 Erin E Michalak,6 Jing Liu,6 Tao Yang,1,2 Xiaorui Yang,7 Yiru Fang,1,8,9 Raymond W Lam,6 Jun Chen1,2 1Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of China; 3Division of Mood Disorders, Shanghai Hongkou Mental Health Center, Shanghai, People’s Republic of China; 4Clinical Research Center for Mental Health, School of Medicine, Shanghai University, Shanghai, People’s Republic of China; 5Fengxian District Mental Health Center, Shanghai, People’s Republic of China; 6Department of Psychiatry, University of British Columbia, Vancouver, Canada; 7Department of Psychology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 8Department of Psychiatry & Affective Disorders Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 9CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, People’s Republic of ChinaCorrespondence: Jun Chen, Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People’s Republic of China, Tel +86 21-34773367, Email doctorcj2010@gmail.com Raymond W Lam, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 2A1, Canada, Tel +1 604-822-7325, Email r.lam@ubc.caPurpose: To validate the efficacy of enhanced measurement-based care against standard measurement-based care in patients with major depressive disorder.Patients and Methods: In this pilot study of an ongoing multicenter cluster randomized controlled trails, 160 patients diagnosed with major depressive disorder were enrolled from 2 mental health centers, with a plan to include 12 centers in total. One hundred patients engaged in a six-month evaluation using a technology-enhanced measurement-based care tool, including assessments of clinical symptoms, side effects, and functionality at baseline, two months, four months and six months. Simultaneously, the remaining 60 patients underwent standard paper-based measurement-based care, utilizing the same set of scales over the same six-month period, with assessments at the same time points.Results: Patients utilizing the enhanced measurement-based care tool demonstrated a significantly higher reduction rate in PHQ-9 scores compared to those using standard paper-based measurement-based care during the two-month follow-up. Additionally, a notable positive correlation was observed between the frequency of enhanced measurement-based care tool usage and the quality of life during the two-month follow-up.Conclusion: Enhanced measurement-based care has the effect of reducing depressive symptoms. Our study emphasized that using enhanced measurement-based care via smartphones is a feasible tool for patients with major depressive disorder. Our future study, including results from additional research centers, may further validate the effectiveness of enhanced measurement-based care.Keywords: major depressive disorder, measurement-based care, enhanced measurement-based care, smartphone-based intervention

Yufeng Liu,1,&ast; Jie Liu,1,&ast; Xiaoyan Wu,1 Enshe Jiang2,3 1Department of Cardiovascular Medicine, Luoyang Central Hospital affiliated to Zhengzhou University, Luoyang, Henan, 471000, People’s Republic of China; 2Department of Neurosurgery, The First Affiliated Hospital of Henan University, Kaifeng, Henan, 475004, People’s Republic of China; 3Institute of Nursing and Health, Henan University, Kaifeng, Henan, 475004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Enshe Jiang, Email esjiang@gmail.comAbstract: The central nervous system (CNS) is less prone to infection owing to protection from the brain-blood barrier. However, craniotomy destroys this protection and increases the risk of infection in the brain of patients who have undergone craniotomy. CNS infection after craniotomy significantly increases the patient’s mortality rate and disability. Controlling the occurrence of intracranial infection is very important for post-craniotomy patients. CNS infection after craniotomy is caused by several factors such as preoperative, intraoperative, and post-operative factors. Craniotomy may lead to postsurgical intracranial infection, which is mainly associated with surgery duration, infratentorial (posterior fossa) surgery, cerebrospinal fluid leakage, drainage tube placement, unregulated use of antibiotics, glucocorticoid use, age, diabetes, and other systemic infections. Understanding the risk factors of CNS infection after craniotomy can benefit reducing the incidence of intracranial infectious diseases. This will also provide the necessary guidance and evidence in clinical practice for planning to control intracranial infection in patients with craniotomy.Keywords: surgery duration, posterior fossa, cerebrospinal fluid leakage, drainage tube, antibiotics, glucocorticoids

Xiaolu Chen,1– 3 Jian Liu,1,2 Guizhen Wang,1,2 Yanqiu Sun,1,2 Xiang Ding,1– 3 Xianheng Zhang1– 3 1Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, 230038, People’s Republic of China; 2Institute of Rheumatology, Anhui University of Chinese Medicine, Hefei, Anhui Province, 230012, People’s Republic of China; 3Anhui University of Traditional Chinese Medicine, Hefei, People’s Republic of ChinaCorrespondence: Jian Liu, Department of Rheumatology and Immunology, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui Province, 230038, People’s Republic of China, Tel +86 551 62838582, Fax +86 551 62821605, Email liujianahzy@126.comObjective: Jianpi Qingre Tongluo Recipe (JQP) has been widely used in clinical practice, and its anti-Osteoarthritis (OA) effectiveness and specific mechanism have been concerned. This study aims to explore the clinical effect of JQP in reducing inflammation and dyslipidemia in OA and the molecular mechanism.Methods: The clinical efficacy of JQP in OA treatment was assessed through data mining. Through the network pharmacology technology, the interactive network of “active component-target-disease” was developed, the interaction relationship of the related proteins was analyzed, and enrichment analysis of gene pathway biological process was conducted. Molecular docking was carried out with PyMOL and AutodockTools-1.5.7. Finally, cell experiments were used to verify JQP’s delay of immune inflammation in OA.Results: We found that JQP could ameliorate the immune inflammatory and lipid metabolism indicators; reduce VAS and SAS score in OA. A total of 98 genes overlapped between target genes of JQP and OA. TNF, IL-6, IL-1β, and AKT1 shared the highest centrality among all target genes. KEGG analysis unveiled that 98 intersection genes were predominantly enriched in PI3K/AKT pathway in the anti-OA system. In vitro, after peripheral blood mononuclear cell (PBMC) stimulation, inflammatory cytokines imbalances and the expressions of adiponectin (APN) were decreased in osteoarthritis-chondrocytes (OA-CH). Furthermore, JQP-containing serum protected OA-CHs through down-regulating HOTAIR levels, thereby up-regulating APN and depressing PI3K/AKT pathway.Conclusion: This study suggests that JQP might reduce inflammation and improve lipid metabolism of OA by regulating HOTAIR/APN/PI3K/AKT. Our results bring a new solution for OA.Keywords: osteoarthritis, chondrocytes, inflammation, LncRNA HOTAIR/APN/PI3K/AKT

Zhenyu Li,1 Jimin Liu,2 Haishan Cui,3 Wenlong Qi,4 Yangyang Tong,4 Tan Wang4 1College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130117, People’s Republic of China; 2Department of Respiratory, The Third Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130117, People’s Republic of China; 3Department of Traditional Chinese Medicine, The Third Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130117, People’s Republic of China; 4Department of Respiratory, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130021, People’s Republic of ChinaCorrespondence: Tan Wang, Department of Respiratory, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, 130021, People’s Republic of China, Email wangtan0215@163.comAbstract: The rising global morbidity and mortality rates of non-small cell lung cancer (NSCLC) underscore the urgent need for more effective treatments. Current therapeutic modalities—including surgery, radiotherapy, chemotherapy, and targeted therapy—face several limitations. Recently, Astragalus membranaceus, a traditional Chinese medicine (TCM), has captured significant attention due to its broad pharmacological properties, such as immune regulation, anti-inflammatory effects, and the modulation of reactive oxygen species (ROS) and enzyme activities. This review delivers a comprehensive summary of the most recent advancements and ongoing applications of Astragalus membranaceus in NSCLC treatment, underlining its potential for integration into existing treatment protocols. It also highlights essential areas for future research, including the elucidation of its molecular mechanisms, optimization of dosage and administration, and evaluation of its efficacy and safety alongside standard therapies, all of which could potentially improve therapeutic outcomes for NSCLC patients.Keywords: non-small cell lung cancer, Astragalus membranaceus, antitumor activity, immunoregulation, cisplatin

Kaifei Chu,1,2,&ast; Jie Liu,2,&ast; Xu Zhang,1,2 Minran Wang,1 Wanping Yu,1 Yuyue Chen,1 Lingling Xu,2 Geng Yang,1 Naru Zhang,1 Tiejun Zhao1,2 1Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, People’s Republic of China; 2College of Life Sciences, Zhejiang Normal University, Jinhua, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tiejun Zhao; Naru Zhang, Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, 310015, People’s Republic of China, Email tjzhao@hzcu.edu.cn; zhangnr@hzcu.edu.cnAbstract: Plant-derived exosome-like nanovesicles (PDNVs) are small nanoscale vesicles containing lipids, RNAs, proteins and some plant natural products secreted by plant cells. Over the last decade, PDNVs have garnered significant interest due to its exceptional therapeutic benefits in the treatment of various diseases. Herbal medicine, as a medicinal plant, plays an important role in the treatment of diseases including cancer. Especially in recent years, the function of herbal medicine derived exosome-like nanovesicles (HMDNVs) in the treatment of cancer has been widely concerned, and has become a research hotspot of nanomedicine. In this review, the biological characteristics, functions and the therapeutic advantages of PDNVs are reviewed, as well as the recent achievements and research progress of HMDNVs in cancer treatment, demonstrating its enormous promise as a cancer therapy, and new insights are provided for future research and development of anti-tumor drugs.Keywords: herbal medicine, plant-derived exosome-like nanovesicles, extracellular vesicles, cancer treatment, nanomedicine

Liang Shan,1– 4 Fengling Wang,1 Dandan Zhai,1 Xiangyun Meng,1 Jianjun Liu,1 Xiongwen Lv2– 4 1Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, China; 2Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China; 3Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, Anhui, 230032, China; 4The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, ChinaCorrespondence: Jianjun Liu, Department of Pharmacy, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, China, Tel/Fax +86 0551 62965335, Email Jianjun_liu2020@163.com Xiongwen Lv, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei, Anhui, 230032, China, Tel/Fax +86 0551 65161000, Email Xiongwen_lv2019@163.comBackground: Biliary atresia (BA) is a severe neonatal progressive cholangiopathy of unknown etiology. A timely Kasai portoenterostomy (KPE) improves survival of the native liver in patients with BA, although liver transplantation remains the ultimate treatment for most (60%– 80%) patients. However, postoperative adverse effects of liver transplantation may be significant. In addition, patients require lifelong immunosuppressive therapy after liver transplantation.Case Summary: Here, we report a case of a newborn female baby (birthday: 10– 03-2018) with congenital BA (confirmed at 76 days of life) who survived KPE (first surgery at 85 days of life) and underwent successful living-related liver transplantation (LRLT) (second surgery at 194 days of life). Additionally, we reviewed the existing literature on BA. After KPE (at 85 days of life), the liver function of the baby did not improve, and the indicators of liver and kidney function showed a trend of aggravation, indicating that the liver function had been seriously damaged before KPE (at 85 days of life), demonstrating the urgent need for liver transplantation surgery. The female baby survived after part of her father’s liver was successfully transplanted into her body (at 194 days of life). The patient recovered successfully. No other diseases were found at the 4-year follow-up, and all indices of liver and kidney functions tended to be normal.Conclusion: This case highlights the following. Postoperative alkaline phosphatase was consistently above the normal range, although the reason for this was unclear; neither tacrolimus nor cyclosporine A has formulations designed specifically for infants, which does not meet the needs of clinical individualized medication, suggesting that these anti-rejection drugs are future development directions. Only one case of congenital BA has been found thus far in Hefei, and this case has extremely important reference significance for the prevention, treatment, and diagnosis of BA in Hefei, Anhui province. Keywords: biliary atresia, Kasai portoenterostomy, living-related liver transplantation, immunosuppressive drug, therapeutic drug monitoring

Ning-ning Xia, Kuei-ching Pan, Jing Liu, Daxi Ji Department of Nephrology, Nanjing BenQ Medical Center, BenQ Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of ChinaCorrespondence: Kuei-ching Pan; Jing Liu, Email PKJ13951672501@126.com; liujing66382@126.comObjective: To investigate current status of quality of life and the association between depression and symptom burden in a sample of Chinese maintenance hemodialysis (MHD) patients.Methods: A self-designed patient general information questionnaire, disease-related information questionnaire, dialysis patient symptom burden scale, depression scale, and quality of survival scale were used to investigate 380 maintenance haemodialysis patients in haemodialysis centres. A regression model of the factors affecting the quality of survival was established using structural equation modelling.Results: The regression model data had a high goodness of fit: c2/df = 4.736, RMSEA = 0.099, GFI = 0.918, CFI = 0.972, TLI = 0.962, SRMR = 0.0469. Structural equation model analysis showed that depression had a positive predictive effect on symptom burden, β = 0.398, P

Shuang Du,1,&ast; Ke Lin,2,&ast; Jing Li,3 Xin Zhou,4 Chaolan Wang,2 Jun Liu,3 Na Li,2 Jian Chen2 1Department of Rehabilitation Medicine, The First People’s Hospital of Jin Tang County, Chengdu, Sichuan, 610400, People’s Republic of China; 2Traditional Chinese Medicine Department, The First People’s Hospital of Jintang County, Chengdu, Sichuan, 610400, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Jintang County, Chengdu, Sichuan, 610400, People’s Republic of China; 4Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Chen, Traditional Chinese Medicine Department, The First People’s Hospital of Jintang County, Chengdu, Sichuan, 610400, People’s Republic of China, Tel +86-10-18908176456, Email chenjian792@163.comPurpose: COPD patients frequently have abnormal serum phosphorus levels. The objective of this study was to examine the correlation between serum phosphorus levels with hospital and 90-day mortality in critically ill patients with COPD.Patients and Methods: The MIMIC IV database was used for this retrospective cohort analysis. We extracted demographics, vital signs, laboratory tests, comorbidity, antibiotic usage, ventilation and scoring systems within the first 24 hours of ICU admission. Restricted cubic splines and multivariate cox regression analysis models were used to evaluate the connection between serum phosphorus with hospital and 90-day mortality. We assessed and classified various factors including gender, age, renal disease, severe liver disease, the utilization of antibiotics and congestive heart failure.Results: We included a total of 3611 patients with COPD, with a median age of 70.7 years. After adjusting for all other factors, we observed a significant positive association between serum phosphate levels with both hospital mortality (HR 1.19, 95% CI: 1.07– 1.31, p< 0.001) and 90-day mortality (HR 1.15, 95% CI: 1.06– 1.24, p< 0.001). Compared to the medium group (Q2 ≥ 3.15, < 4.0), the adjusted hazard ratios for hospital mortality were 1.47 (95% CI: 1.08– 2, p=0.013), and 1.31 (95% CI: 1.06– 1.61, p=0.013) for 90-day mortality in the high group (Q3≥ 4.0). Hospital mortality decreased at serum phosphate levels below 3.8 mg/dl (HR 0.664, 95% CI: 0.468– 0.943, p=0.022), but increased for both hospital (HR 1.312, 95% CI: 1.141– 1.509, p< 0.001) and 90-day mortality (HR 1.236, 95% CI: 1.102– 1.386, p< 0.001) when levels were above 3.8 mg/dl. Subgroup and sensitivity analyses yielded consistent results.Conclusion: In critical ill COPD patients, this study demonstrated a non-linear association between serum phosphate levels and both hospital and 90-day mortality. Notably, there was an inflection point at 3.8 mg/dl, indicating a significant shift in outcomes. Future prospective research is necessary to validate this correlation.Keywords: COPD, serum phosphate, mortality, MIMIC-IV, critically ill

Lixia Li,1,&ast; Xiaohui Huang,1,&ast; Jingxian Liu,2,&ast; Chao Li,1 Zhiyan Lin,1 Rongrong Ren,3 Yan Zhang,3 Haoshu Ding,3 Jihui Chen,1 Yanfei Mao3 1Department of Pharmacy, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Clinical Laboratory, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Anesthesiology and SICU, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanfei Mao; Jihui Chen, Email maoyanfei@xinhuamed.com.cn; chenjihui@xinhuamed.com.cnBackground: Polymyxin B (PMB)-based combination therapies are used to treat severe carbapenem-resistant gram-negative bacterial (CR-GNB) infections. This observational study investigated the relationship between clinical factors, including PMB concentration, and clinical efficacy and safety.Patients and Methods: Polymyxin B regimens were optimized through therapeutic drug monitoring (TDM) and area under the concentration-time curve (AUC). In all, 382 samples were tested from 130 patients. Logistic regression was used to analyze the relationships between variables with clinical efficacy and 30-day mortality factors were analyzed by Cox regression. The sensitivity and specificity of Cmin and AUC for the occurrence of acute kidney injury (AKI) were determined by ROC curve analysis.Results: The clinical effectiveness of PMB was 65.4%. Multivariate logistic regression analysis revealed that lung infection, continuous renal replacement therapy, and C-reactive protein were independent factors significantly associated with efficacy. AKI occurred in 14.6% of the patients during treatment; age > 73 years (OR: 3.63; 95% CI: 1.035– 12.727; P = 0.044), Cmin greater than 2.3 μg/mL (OR: 7.37; 95% CI: 1.571– 34.580; P = 0.011), combined vancomycin (OR: 9.47; 95% CI: 1.732– 51.731; P = 0.009), and combined piperacillin-tazobactam (OR: 21.87; 95% CI: 3.139– 152.324; P = 0.002) were independent risk factors. The identified PMB cut-offs for predicting AKI were Cmin = 2.3 μg/mL and AUC = 82.0 mg h/L.Conclusion: Polymyxin B-based combination regimens are effective in treating CR-GNB infections, particularly bloodstream infections, but have shown unsatisfactory for lung infections. Cmin ≥ 2.3 μg /mL and AUC ≥ 82.0 mg h/L may increase PMB-associated AKI incidence. PMB dose should be adjusted based on TDM to ensure efficacy.Keywords: Polymyxin B, PMB therapeutic drug monitoring, TDM, carbapenem-resistant gram-negative bacteria, CR-GNB, clinical efficacy, acute kidney injury, AKI

Yun Han,1,&ast; Jianping Zhu,1,&ast; Jieqiong Liu,2 Ying Zheng,2 Gang Liang,1 Yi Yang,1 Lingyan Yu,3 Zhenwei Yu,1 Gang Han1 1Research Center for Clinical Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of China; 2The 903rd Hospital of PLA Joint Logistic Support Force, Hangzhou, People’s Republic of China; 3Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenwei Yu; Gang Han, Email yzw_srrsh@zju.edu.cn; 3199022@zju.edu.cnIntroduction: Recent studies suggested the potential benefits of extended infusion times to optimize the treatment efficacy of ceftazidime/avibactam, which indicated that the current pharmacokinetic/pharmacodynamic (PK/PD) target may not be sufficient, especially for severe infections. The purpose of this study is to assess the adequacy of dosing strategies and infusion durations of ceftazidime/avibactam when applying higher PK/PD targets.Methods: This study utilized published PK parameters to conduct Monte Carlo simulations. Different dosages including the recommended regimen based on renal function were simulated and evaluated by the probability of target attainment (PTA) and cumulative fraction of response (CFR). Different PK/PD targets were set for ceftazidime and avibactam. MIC distributions from various sources were used to calculate the CFR.Results: Multiple PK/PD targets have been set in this study, All recommended dosage could easily achieve the target of 50%fT ≥ MIC (ceftazidime) and 50%fT ≥ CT=1.0 mg/L (avibactam). However, for severe infection patients with normal renal function and augmented renal clearance at the recommended dosage (2000 mg/500 mg, every 8 hours), the infusion duration needs to be extended to 3 hours and 4 hours to achieve the targets of 100%fT ≥ MIC and 100%fT ≥ CT=1.0 mg/L. Only continuous infusion at higher dosages achieved 100%fT ≥ 4×MIC and 100%fT ≥ CT=4.0 mg/L targets to all currently recommended regimens. According to the varying MIC distributions, higher concentrations are needed for Pseudomonas aeruginosa, with the attainment rates vary across different regions.Conclusion: The current recommended dosing regimen of ceftazidime/avibactam is insufficient for severe infection patients, and continuous infusion is suggested.Keywords: ceftazidime, avibactam, pharmacokinetic/pharmacodynamic, probability of target attainment

Jilei Li,1,&ast; Wenchao Dan,2,&ast; Chenchen Zhang,3 Nian Liu,3 Yichong Wang,1 Jixiang Liu,3 Shengsheng Zhang1 1Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China; 2Department of Dermatology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China; 3Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengsheng Zhang, Digestive Disease Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, Tel +8613801088329, Email zhangshengsheng@bjzhongyi.comPurpose: This study aimed to delineate the molecular processes underlying the therapeutic effects of berberine on UC by employing network pharmacology tactics, molecular docking, and dynamic simulations supported by empirical validations both in vivo and in vitro.Patients and Methods: We systematically screened potential targets and relevant pathways affected by berberine for UC treatment from comprehensive databases, including GeneCards, DisGeNET, and GEO. Molecular docking and simulation protocols were used to assess the interaction stability between berberine and its principal targets. The predictions were validated using both a DSS-induced UC mouse model and a lipopolysaccharide (LPS)-stimulated NCM460 cellular inflammation model.Results: Network pharmacology analysis revealed the regulatory effect of the TLR4/NF-κB/HIF-1α pathway in the ameliorative action of berberine in UC. Docking and simulation studies predicted the high-affinity interactions of berberine with pivotal targets: TLR4, NF-κB, HIF-1α, and the HIF inhibitor KC7F2. Moreover, in vivo analyses demonstrated that berberine attenuates clinical severity, as reflected by decreased disease activity index (DAI) scores, reduced weight loss, and mitigated intestinal inflammation in DSS-challenged mice. These outcomes include suppression of the proinflammatory cytokines IL-6 and TNF-α and downregulation of TLR4/NF-κB/HIF-1α mRNA and protein levels. Correspondingly, in vitro findings indicate that berberine decreases cellular inflammatory injury and suppresses TLR4/NF-κB/HIF-1α signaling, with notable effectiveness similar to that of the HIF-1α inhibitor KC7F2.Conclusion: Through network pharmacology analysis and experimental substantiation, this study confirmed that berberine enhances UC treatment outcomes by inhibiting the TLR4/NF-κB/HIF-1α axis, thereby mitigating inflammatory reactions and improving colonic pathology. Keywords: berberine, ulcerative colitis, TLR4/NF-κB/HIF-1α, network pharmacology, molecular docking, experimental validation, inhibitor

Meng Zhang,1,2 Qi Yuan,1 Peiwen Wang,1 Fan Zhang,1 Dan Wu,1 He Bai,1 Jieting Liu,1 Haifeng Liu,1 Xiaohuan Yuan1 1College of Life Science, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 2The First Hospital of Qiqihar, Qiqihar, People’s Republic of ChinaCorrespondence: Xiaohuan Yuan, College of Life Science, Mudanjiang Medical University, No. 3 Tongxiang Road, Mudanjiang, 157011, People’s Republic of China, Tel/Fax +86-453-6984401, Email yuanxiaohuan@mdjmu.edu.cnPurpose: Nanovesicles (NVs) derived from bone mesenchymal stem cells (BMSCs) as drug delivery systems are considered an effective therapeutic strategy for diabetes. However, its mechanism of action remains unclear. Here, we evaluated the efficacy and molecular mechanism of BMSC-derived NVs carrying the curcumin analog H8 (H8-BMSCs-NVs) on hepatic glucose and lipid metabolism in type 2 diabetes (T2D).Subjects and Methods: Mouse BMSCs were isolated by collagenase digestion and H8-BMSCs-NVs were prepared by microvesicle extrusion. The effects of H8-BMSCs-NVs on hepatic glucose and lipid metabolism were observed in a T2D mouse model and a HepG2 cell insulin resistance model. To evaluate changes in potential signaling pathways, the PI3K/AKT/AMPK signaling pathway and expression levels of G6P and PEPCK were assessed by Western blotting.Results: H8-BMSCs-NVs effectively improved lipid accumulation in liver tissues and restored liver dysfunction in T2D mice. Meanwhile, H8-BMSCs-NVs effectively inhibited intracellular lipid accumulation in the insulin resistance models of HepG2 cells. Mechanistic studies showed that H8-BMSCs-NVs activated the PI3K/AKT/AMPK signaling pathway and decreased the expression levels of G6P and PEPCK.Conclusion: These findings demonstrate that H8-BMSCs-NVs improved hepatic glucose and lipid metabolism in T2D mice by activating the PI3K/AKT/AMPK signaling pathway, which provides novel evidence suggesting the potential of H8-BMSCs-NVs in the clinically treatment of T2D patients.Keywords: bone mesenchymal stem cell, nanovesicles, curcumin analogue H8, type 2 diabetes

Luxun Yang,1,&ast; Haiying Ran,2,&ast; Yaru Yin,1 Jing Liu,1 Binghui Lu,1 Xi Ran,3 Shenglin Luo,1 Weidong Wang,4 Zhangyou Yang,5 Rong Li1 1Institute of Combined Injury, National Key Laboratory of Trauma and Chemical Poisoning, Army Key Laboratory of Nanomedicine, Department of Military Preventive Medicine, Army Medical University, Chongqing, 400038, People’s Republic of China; 2Biomedical Analysis Center, Army Medical University, Chongqing, 400038, People’s Republic of China; 3Department of Medical Laboratory, Xinqiao Hospital, Army Medical University, Chongqing, 400037, People’s Republic of China; 4Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu, 610041, People’s Republic of China; 5Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing Pharmacodynamic Evaluation Engineering Technology Research Center, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhangyou Yang, Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing, 400016, People’s Republic of China, Email yangzhangyou@cqmu.edu.cn Rong Li, Army Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, People’s Republic of China, Tel +86-13883996627, Fax +8623-68753127, Email lrong361@126.comPurpose: Mitochondrial oxidative stress is an important factor in cell apoptosis. Cerium oxide nanomaterials show great potential for scavenging free radicals and simulating superoxide dismutase (SOD) and catalase (CAT) activities. To solve the problem of poor targeting of cerium oxide nanomaterials, we designed albumin-cerium oxide nanoclusters (TPP-PCNLs) that target the modification of mitochondria with triphenyl phosphate (TPP). TPP-PCNLs are expected to simulate the activity of superoxide dismutase, continuously remove reactive oxygen species, and play a lasting role in radiation protection.Methods: First, cerium dioxide nanoclusters (CNLs), polyethylene glycol cerium dioxide nanoclusters (PCNLs), and TPP-PCNLs were characterized in terms of their morphology and size, ultraviolet spectrum, dispersion stability and cellular uptake, and colocalization Subsequently, the anti-radiation effects of TPP-PCNLs were investigated using in vitro and in vivo experiments including cell viability, apoptosis, comet assays, histopathology, and dose reduction factor (DRF).Results: TPP-PCNLs exhibited good stability and biocompatibility. In vitro experiments indicated that TPP-PCNLs could not only target mitochondria excellently but also regulate reactive oxygen species (ROS)levels in whole cells. More importantly, TPP-PCNLs improved the integrity and functionality of mitochondria in irradiated L-02 cells, thereby indirectly eliminating the continuous damage to nuclear DNA caused by mitochondrial oxidative stress. TPP-PCNLs are mainly targeted to the liver, spleen, and other extramedullary hematopoietic organs with a radiation dose reduction factor of 1.30. In vivo experiments showed that TPP-PCNLs effectively improved the survival rate, weight change, hematopoietic function of irradiated animals. Western blot experiments have confirmed that TPP-PCNLs play a role in radiation protection by regulating the mitochondrial apoptotic pathway.Conclusion: TPP-PCNLs play a radiologically protective role by targeting extramedullary hematopoietic organ-liver cells and mitochondria to continuously clear ROS.Keywords: radioprotective effect, ceria nanoclusters, mitochondria targeting, oxidative stress, superoxide dismutase

Haisong Hou,1,2 Liu Liang,3 Lihong Deng,4 Wanping Ye,5 Yuanzhang Wen,6 Jun Liu1 1Laboratory of Pathogenic Biology, Guangdong Medical University, Zhanjiang, People’s Republic of China; 2Department of Blood Transfusion, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 4Department of Hepatology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 5Department of Gastroenterology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 6Department of Hepatobiliary Surgery, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Jun Liu, Laboratory of Pathogenic Biology, Guangdong Medical University, Zhanjiang, People’s Republic of China, Email liujungd6@163.comBackground: The aim of this study was to describe the demographic and clinical characteristics of hepatitis B virus (HBV) associated hepatocellular carcinoma (HCC), analyse the risk factors associated with HBV-associated HCC, and to provide some references to the diagnosis and treatment of HCC.Methods: This study retrospectively enrolled 730 patients, including 390 patients with chronic hepatitis B (CHB) as controls, and 340 patients with CHB complicated with HCC as patients. Relevant information and medical records of these participants were collected, including age, sex, cigarette smoking, alcoholism, diabetes mellitus (DM), hypertension, coronary heart disease (CHD), cirrhosis, occupation, ascites, HBV-DNA load, the qualitative analysis of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb serological markers, and levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), gamma-glutamyltransferase (GGT), TNM stage, tumor size and tumor number. The T test, Chi-square test, non-parametric rank-sum test, logistic regression analyses were used to explore the influencing factors and their degree of association with HCC in patients with HBV.Results: The proportion of smoking, alcoholism, married status, DM, hypertension, and the rate of HBV-DNA with a viral load of ≥ 500 copies/mL were significantly higher in the HCC group than in the controls (all p< 0.05). Cirrhosis was more common among patients with CHB+HCC than in controls (p=0.013). The proportion of patients with HBsAg, HBeAb, and HBcAb positive was greater in CHB+HCC group than that in CHB group. Logistic regression analysis indicated that age ≥ 60 years (OR: 1.835, 95% CI: 1.020– 3.302, p=0.043), HBeAb positive (OR: 9.105, 95% CI: 4.796– 17.288, p< 0.001), antiviral treatment with entecavir (OR: 2.209, 95% CI: 1.106– 4.409, p=0.025), and GGT (OR: 1.004, 95% CI: 1.001– 1.007, p=0.002) were risk factors for HCC in patients with CHB.Conclusion: Advanced age, HBeAb positive, antiviral treatment with entecavir, and GGT were independent risk factors for HCC in HBV patients.Keywords: chronic hepatitis B, hepatocellular carcinoma, cirrhosis, hepatitis B virus

Wanlan Fu,1 Yunxiang Cao,2 Jian Liu,2 Chuanbing Huang,2 Kaiyan Shu,1 Nanfei Zhu1 1First Clinical Medical College, Anhui University of Chinese Medicine, Hefei, Anhui, 230012, People’s Republic of China; 2Department of Rheumatology, First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, 230031, People’s Republic of ChinaCorrespondence: Yunxiang Cao, Department of Rheumatology, First Affiliated Hospital of Anhui University of Chinese Medicine, 117 Meishan Road, Shushan District, Hefei, Anhui, 230031, People’s Republic of China, Tel +86-13514984395 ; +0551-62838591, Email cyx800805@163.comPurpose: This study probed the mechanism of action of Xinfeng Capsule (XFC) in myocardial injury in rats with adjuvant arthritis (AA) via the growth arrest-specific transcript 5 (GAS5)/microRNA-21 (miR-21)/Toll-like receptor 4 (TLR4) axis.Methods: Rats were injected with Freund’s complete adjuvant to establish a rat model of AA. Then, some modeled rats were given normal saline or drugs only, and some modeled rats were injected with adeno-associated viruses or necrosulfonamide (NSA; a pyroptosis inhibitor) before drug administration. Toe swelling and arthritis index (AI) were calculated. Pathological and morphological changes in synovial and myocardial tissues were analyzed with hematoxylin-eosin staining, and pyroptotic vesicles and the ultrastructural changes of myocardial tissues were observed with transmission electron microscopy. The serum levels of interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor (TNF)-α were detected, and lactate dehydrogenase (LDH) release was measured in myocardial tissues, accompanied by the examination of GAS5, miR-21, TLR4, nuclear factor-kB (NF-κB) p65, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), Caspase-1, and Gasdermin D (GSDMD) expression in myocardial tissues.Results: After AA modeling, rats presented with significantly increased toe swelling and AI scores, synovial and myocardial tissue damage, elevated pyroptotic vesicles, and markedly enhanced serum levels of IL-1β, IL-18, IL-6, and TNF-α, accompanied by significantly diminished GAS5 expression, substantially augmented miR-21, TLR4, NF-κB p65, NLRP3, Caspase-1, and GSDMD expression, greatly increased LDH release in myocardial tissues. XFC treatment significantly declined toe swelling, AI scores, synovial and myocardial tissue damage, and the serum levels of IL-1β, IL-18, IL-6, and TNF-α in AA rats. Additionally, XFC treatment markedly elevated GAS5 expression and substantially lowered LDH release and miR-21, TLR4, NF-κB p65, NLRP3, Caspase-1, and GSDMD expression in myocardial tissues of AA rats. Moreover, the above effects of XFC in AA rats were further promoted by GAS5 overexpression or NSA treatment.Conclusion: XFC alleviated myocardial injury in AA rats by regulating the GAS5/miR-21/TLR4 axis and inhibiting pyroptosis and pro-inflammatory cytokine secretion.Keywords: adjuvant arthritis, myocardial injury, GAS5/miR-21/TLR4 axis, pyroptosis, Xinfeng Capsule

Xundi Bao,1 Shuo Liang,1 Jun Li,1 Qian Ye,1 Dandan Wu,1 Shu Wang,2 Yue Li,1 Yunsheng Ding,1 Jie Liu3 1Clinical Laboratory, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), Hefei, Anhui, People’s Republic of China; 2Department of Science and Education, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), Hefei, Anhui, People’s Republic of China; 3Tuberculosis Control Institute, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), Hefei, Anhui, People’s Republic of ChinaCorrespondence: Xundi Bao, Clinical laboratory, Anhui Provincial Chest Hospital (Provincial Institute of Tuberculosis Control), No. 397, Jixi Road, Shushan District, Hefei, Anhui, People’s Republic of China, Tel +86-13866774716, Email baoxundi@163.comObjective: To preliminarily assess the prevalence and control effect of tuberculosis and drug-resistant tuberculosis (TB) in Anhui province, and analyze the trends in the changing drug resistance spectrum of Mycobacterium tuberculosis (Mtb) isolated in Anhui province from 2016 to 2022.Methods: From 2016 to 2022, a total of 2336 culture-positive tuberculosis strains were collected from four drug resistance monitoring sites. Patient demographic information was collected and drug susceptibility testing was conducted.Results: Among the 2336 Mycobacterium tuberculosis complex strains, 1788 (76.54%) were from male patients and 548 (23.46%) were from female patients. The majority were of Han ethnicity, from rural areas, and employed in agriculture, with 12.54% (285/2273) having diabetes. A total of 1893 (81.04%) strains were sensitive to all six anti-TB drugs tested, and 443 (18.96%) strains were resistant to at least one or more anti-TB drugs. The drug resistance rate for patients undergoing initial treatment was 16.80% (348/2071), and 35.85% (95/265) for those receiving retreatment. Among the six anti-TB drugs, the resistance rates from highest to lowest were: INH (10.55%, 236/2336), SM (8.18%, 183/2336), OFX (6.53%, 146/2336), RFP (5.95%, 133/2336), EMB (2.37%, 53/2336), KM (1.97%, 44/2336). Significant differences were observed in MDR strains across different ages, types, with or without diabetes, and geographical sources (χ 2=14.895,76.534,6.032,5.109, all P< 0.05).Conclusion: The tuberculosis prevention and control measures have controlled the drug resistance rate of Mycobacterium tuberculosis to a certain extent. However, there are still statistical differences in drug resistance rates among TB patients with different categories, age groups, regions, and diabetic diseases. Early detection and prompt treatment of patients with drug-resistant TB remain critical to controlling the spread of this disease.Keywords: tuberculosis, mycobacterium, drug resistance, surveillance, population distribution, characteristic analysis

Xiaodong Zhu,1 Ya Huang,2 Jia Ding,1 Jianguo Liu,1 Changmeng Cui,1 Guangkui Han1 1Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China; 2College of Traditional Chinese Medicine, Shandong Polytechnic College, Jining, 272000, People’s Republic of ChinaCorrespondence: Guangkui Han, Department of Neurosurgery, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, Shandong, 272000, People’s Republic of China, Tel +8618266808351, Email hanguangkui1997@163.comPurpose: SN-38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan, has been extensively studied in drug delivery systems. However, its impact on neural metabolism remains unclear. This study aims to investigate the toxic effects of SN-38 on mouse brain metabolism.Methods: Male mice were divided into an SN-38 group and a control group. The SN-38 group received SN-38 (20 mg/kg/day) via intraperitoneal injection, while the control group was given an equal volume of a blank solvent mixture (DMSO and saline, ratio 1:9). Gas chromatography-mass spectrometry (GC-MS) was employed to analyze differential metabolites in the cortical and hippocampal regions of the SN-38-treated mice.Results: SN-38 induced metabolic disturbances in the central nervous system. Eighteen differential metabolites were identified in the hippocampus and twenty-four in the cortex, with six common to both regions. KEGG pathway enrichment analysis revealed statistically significant alterations in six metabolic pathways in the hippocampus and ten in the cortex (P< 0.05).Conclusion: This study is the first to demonstrate the neurotoxicity of SN-38 in male mice through metabolomics. Differential metabolites in the hippocampal and cortical regions were closely linked to purine metabolism, pyrimidine metabolism, amino acid metabolism, and glyceride metabolism, indicating disruptions in the blood-brain barrier, energy metabolism, and central signaling pathways.Keywords: SN-38 (7-ethyl-10-hydroxycamptothecin), biomarker, gas chromatography mass spectrometry, metabolomics, toxicity mechanism

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

Jing Liu,1,&ast; Tingting Hu,2,3,&ast; Yulan Guan,2,4 Jinguo Zhai2 1Department of Gynecology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510700, People’s Republic of China; 2School of Nursing, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 3Department of Gynecology, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People’s Republic of China; 4Department of Gynecology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, 510105, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yulan Guan, Department of Gynecology, Guangdong Provincial Hospital of Chinese Medicine, No. 261 Datong Road, Yuexiu District, Guangzhou, 510105, People’s Republic of China, Tel +8615989117143, Email 15989117143@163.com Jinguo Zhai, Nursing School, Southern Medical University, No. 1023-1063 Sha Tai Nan Road, Baiyun District, Guangzhou, 510515, People’s Republic of China, Tel +8618620287620, Email helenjxzhai@gmail.comPurpose: To explore the risk and protective factors for developing ovarian cancer and construct a risk prediction model.Methods: Information related to patients diagnosed with ovarian cancer on the electronic medical record data platform of three tertiary hospitals in Guangdong Province from May 2018 to September 2023 was collected as the case group. Patients with non-ovarian cancer who attended the clinic during the same period were included in the control group. Logistic regression analysis was used to screen the independent variables and explore the factors associated with the development of ovarian cancer. An ovarian cancer risk prediction model was constructed using a decision tree C4.5 algorithm. The ROC and calibration curves were plotted, and the model was validated.Results: Logistic regression analysis identified independent risk and protective factors for ovarian cancer. The sample size was divided into training and test sets in a ratio of 7:3 for model construction and validation. The AUC of the training and test sets of the decision tree model were 0.961 (95% CI:0.944– 0.978) and 0.902 (95% CI:0.840– 0.964), respectively, and the optimal cut-off values and their coordinates were 0.532 (0.091, 0.957), and 0.474 (0.159, 0.842) respectively. The accuracies of the training and test sets were 93.3% and 84.2%, respectively, and their sensitivities were 95.7% and 84.2%, respectively.Conclusion: The constructed ovarian cancer risk prediction model has good predictive ability, which is conducive to improving the efficiency of early warning of ovarian cancer in high-risk groups.Keywords: ovarian cancer, incidence factors, decision tree model, risk prediction