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Xinyu Wu,1 Lina Zhang,2 Zangong Zhou,1 Lijie Qi,1 Yinhuan Liu,1 Xuebin Du,1 Lixia Ma,1 Xiangyu Ji1 1Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 2Department of Anesthesiology, Qingdao Municipal Hospital, Qingdao, Shandong, People’s Republic of ChinaCorrespondence: Xiangyu Ji, Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Shandong, People’s Republic of China, Email jixiangyu@qdu.edu.cnPurpose: We conducted a prospective, real-world study to evaluate the efficacy and safety of balanced propofol sedation (BPS) in bronchoscopy and identify an advantageous sedation regimen for such procedures.Patients and Methods: The participants were placed in four groups based on their sedation regimen (exposure factor): the M-S group (midazolam + sufentanil for traditional sedation), R-S group (remimazolam + sufentanil for traditional sedation), M-S-P group (midazolam + sufentanil + propofol for BPS), and R-S-P group (remimazolam + sufentanil + propofol for BPS). The primary outcomes included satisfaction metrics (satisfaction of the patients, endoscopic physicians, and nurses) and follow-up questionnaires. The secondary outcomes included time metrics (induction time, recovery time, and discharge time), dosage metrics (induction dose, maintenance dose, and total dose of each sedative), completion rate of sedation, intraprocedural dose, and frequency of lidocaine spray in the airway, and incidence of adverse reactions.Results: In total, 418 subjects were included in this study. Compared to traditional sedation, both BPS groups significantly increased the satisfaction of patients, endoscopic physicians, and nurses (P < 0.05) and reduced the incidence of intraprocedural wakefulness (P < 0.05). Additionally, induction and recovery of the BPS group were rapid, with high sedation completion rates and no increase in the incidence of intraprocedural and postprocedural adverse reactions (P < 0.05). The RSP group was better than the MSP group in terms of various time metrics and postprocedural adverse reactions.Conclusion: BPS can be safely and effectively applied during bronchoscopy, with remimazolam and sufentanil combined with a small dose of propofol being an optimal medication regimen.Keywords: balanced propofol sedation, bronchoscopy, remimazolam, midazolam, procedural sedation

Peikun Teng,1 Yuzhan Liu,1 Xingyu Zhang,2 Nianxu Luan,1 Xiudi Han,1 Xuedong Liu1 1Department of Respiratory and Critical Care Medicine, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, 266000, People’s Republic of China; 2Human Resources Department, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, 266000, People’s Republic of ChinaCorrespondence: Xuedong Liu; Xiudi Han, Department of Respiratory and Critical Care Medicine, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao, 266000, People’s Republic of China, Tel +86-18661678256 ; +86-15315002781, Email xuedongliu@263.net; hanxiudi@163.comPurpose: Increased clinical manifestations combined with increased lung imaging findings during antifungal therapy are often misjudged as failure of antifungal therapy, and should be vigilant against immune reconstitution inflammatory syndrome.Case: We describes a case of invasive pulmonary Aspergillus infection after Influenza A Virus (IAV). After active antifungal therapy, the patient’s clinical symptoms continued to worsen, imaging lesions continued to progress, laboratory indicators improved, and immune reconstitution inflammatory syndrome was considered.Conclusion: The clinical characteristics and treatment process of this case were summarized, and related literature search was carried out, in order to provide a new perspective for the treatment failure of fungal infection in the future, and to avoid the random change of antifungal drugs, which may lead to the increase of drug resistance.Keywords: Aspergillus infection, influenza A virus, immune reconstitution inflammatory syndrome

Lin Hang,1,2 Abuduwupuer Haibier,1,2 Aiben Kayierhan,1,2 Yuntao Liu,1,2 Tuerhongjiang Abudurexiti1,2 1Minimally Invasive Spinal Surgery, Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, People’s Republic of China; 2Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, People’s Republic of ChinaCorrespondence: Tuerhongjiang Abudurexiti, Email ta272@163.comObjective: To compare the efficacy of anterior and posterior surgery for thoracolumbar tuberculosis disease.Methods: Clinical data of 30 patients with thoracolumbar tuberculosis disease undergoing anterior and posterior surgery from January 2021 to December 2023 were collected for a retrospective study. According to the two surgical procedures, patients were divided into two groups: 1) anterior group (n=15) and 2) posterior group (n=15). We compared the two groups regarding age, gender, body mass index, affected segments, past history (cardiovascular and cerebrovascular diseases, respiratory diseases, endocrine system diseases, metabolic diseases, and tuberculosis history), smoking history, drinking history, operation time, postoperative bleeding, postoperative drainage, postoperative time, postoperative complications (dural tear, lower limb intermuscular vein thrombosis, lower limb deep vein thrombosis, sinus infection, postoperative recurrence rate), and waist VAS score before and after surgery, waist ODI score, and JOA score.Results: The intraoperative blood loss was significantly less in the posterior group than in the anterior group, and the difference was significant (P < 0.05); the lumbar VAS score was lower in the posterior group than in the anterior group, and the difference between the two groups was significant (P < 0.05). The analysis of the remaining data showed no significant difference between the two groups (P> 0.05), indicating that the efficacy of the two procedures was the same.Conclusion: In the treatment of thoracolumbar tuberculosis disease, there is no significant difference in the clinical efficacy of anterior surgery and posterior surgery. Intraoperative bleeding in posterior surgery was less than in anterior surgery, but the latter showed a significant improvement in postoperative pain relief. Therefore, spinal surgeons should choose the corresponding surgical treatment according to the actual situation of the patient in order to maximize the efficacy.Keywords: thoracolumbar spine tuberculosis disease, anterior approach, posterior approach, lesion removal

Yaoli Liu,1 Haimei Lun,1,2 Xuanzhang Huang,1 JianYuan Huang,1 Shangyong Zhu1 1Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Ultrasound, People’s Hospital of Guangxi Zhuang Autonomous Region & Guangxi Academy of Medical Sciences, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Shangyong Zhu, Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-771-5356899, Email zhushangyonggx@163.comObjective: To explore the imaging manifestations and clinical application value of contrast-enhanced ultrasound (CEUS) in liver metastases of middle and low rectal cancer by performing CEUS in patients. Additionally, we compared the results of CEUS with those of abdominal contrast-enhanced computed tomography (CECT) to assess the reliability of diagnosing liver metastases in patients with middle and low rectal cancer.Methods: Hepatic CEUS was performed in 1095 patients with middle and low rectal cancer, and all patients underwent abdominal CECT examinations to determine the presence or absence of liver metastases. The results of both examinations were compared to evaluate the value of hepatic CEUS for detecting liver metastases in patients with middle and low rectal cancer.Results: Among 1095 patients with middle and low rectal cancer, 132 were diagnosed with liver metastases of middle and low rectal cancer. 130 cases of liver metastases of rectal cancer were identified using hepatic CEUS, whereas 126 cases were identified using abdominal CECT. The detection rates of hepatic CEUS and abdominal CECT for liver metastases of middle and low rectal cancer showed no statistically significant differences (P > 0.05). The Kappa value for the diagnosis of liver metastases of middle and low rectal cancer between hepatic CEUS and abdominal CECT was 0.974 (P < 0.001), indicating good consistency between the two imaging modalities in detecting liver metastases of middle and low rectal cancer.Conclusion: Hepatic CEUS can be used to diagnose liver metastases in middle and low rectal cancer, providing crucial imaging evidence for clinical treatment planning. It exhibited higher sensitivity than that of abdominal CECT in diagnosing liver metastases of middle and low rectal cancer, enabling the identification of higher number of liver metastases of middle and low rectal cancer cases.Keywords: middle and low rectal cancer, hepatic CEUS, abdominal CECT, liver metastases

Haoyi Xu,1 Yan Ma,2 Huiling Li,1 Xinyu Song,1 Yuanjing Liu,1 Zuliyaer Mierzhakenmu,1 Kang Yan,1 Rui Xu,1 Ziqian Zhao,1 Hongyi Yuan,1 Chao Dong1 1Department of Breast and Thyroid Surgery, the Third Clinical Medical College of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China; 2Department of Gynecological Surgery, the Third Clinical Medical College of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of ChinaCorrespondence: Chao Dong, Department of Breast and Thyroid Surgery, the Third Clinical Medical College of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China, Tel +86 139 9911 1211, Email dc_dongchao@outlook.comObjective: Triple-negative breast cancer (TNBC) lacks effective targeted, endocrine therapeutic agents and the development of novel agents is costly and time-consuming. The objective of this study was to identify pharmaceuticals and natural products utilized in clinical practice that have the potential to inhibit the expression of Cellular-myelocytomatosis oncogene (c-Myc), based on a review of the current literature. The aim was to assess the effect of the specified drugs on c-Myc expression in TNBC cells, determine the most potent inhibitor, and evaluate its impact on TNBC cell proliferation, invasive migration, and apoptosis, as well as the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) at both the gene and protein levels. Explore its potential for treatment or adjuvant therapy for triple-negative breast cancer.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to quantify gene and protein expression levels. Flow cytometry was employed to measure cell proliferation and apoptosis, while the Transwell assay was utilized to assess cell invasion and migration.Results: Harmaline emerged as the strongest inhibitor, significantly decreasing the expression of c-Myc at both the gene and protein levels in TNBC cells. It also inhibited cell proliferation, invasion, and migration while promoting apoptosis in TNBC cells. Additionally, there was a varying increase in the expression of ER and PR genes and proteins. While the expression of the HER-2 gene was elevated, there was no significant change in HER-2 protein levels. Notably, the expression of the phosphorylated HER-2 protein increased.Conclusion: Harmaline was found to promote apoptosis and inhibit cell proliferation, invasion, and migration in TNBC cells by targeting the inhibition of c-Myc. It also induced the re-expression of the ER, PR, and HER-2 genes, as well as the ER and PR proteins.Keywords: c-Myc, harmaline, molecular typing, triple-negative breast cancer

Xiangying Wang,1 Xiaodan Geng,2 Hui Zhang,3 Yun Liu,4 Zixuan Liu,5 Changsheng Yang1 1Department of Orthopedic Oncology Surgery, Shandong Cancer Hospital and Institute Affiliated to Shandong First Medical University and Shandong Academy of Medical Science, Jinan, 250117, People’s Republic of China; 2Department of Radiology, Shandong Cancer Hospital and Institute Affiliated to Shandong First Medical University and Shandong Academy of Medical Science, Jinan, 250117, People’s Republic of China; 3Department of Medical Oncology, Shandong First Medical University Affiliated Cancer Hospital, Shandong Provincial Cancer Institute and Hospital, Shandong Provincial Tumor Hospital, Jinan, 250117, People’s Republic of China; 4Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China; 5Department of Proctology, Beijing Shunyi Hospital, Beijing, 101300, People’s Republic of ChinaCorrespondence: Changsheng Yang, Department of Orthopedic Oncology Surgery, Shandong Cancer Hospital and Institute Affiliated to Shandong First Medical University and Shandong Academy of Medical Science, Jinan, 250117, People’s Republic of China, Email yangcs521@126.comBackground: Juvenile xanthogranuloma is a rare condition, and femoral involvement is even rarer. We report a case of juvenile xanthogranuloma affecting the femur. To the best of our knowledge, this is the first reported case of femoral juvenile xanthogranuloma in China.Case Presentation: A 19-year-old boy began experiencing swelling in various parts of his body at the age of 1 year, followed by pain in his left hip. Preoperative pathology and imaging indicated juvenile xanthogranuloma of the left femur, leading to surgical intervention. Postoperatively, the patient experienced significant relief from left hip discomfort.Conclusion: Surgery can be an effective treatment for juvenile xanthogranuloma involving the femur.Keywords: juvenile xanthogranuloma, femur, rare case

Bin Dong,1,&ast; Hongsheng Xia,1,&ast; Ying Liu,2 Hailiang Tao,1 Yan Xia,1 Feifei Zhu1 1Department of Ultrasound, Hangzhou Third People’s Hospital, Hangzhou Third Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People’s Hospital(Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Liu, Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People’s Hospital(Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China, Email sag1002@126.comBackground: Dermatofibroma (DF) is one of the common dermatosis, which is so challenging to diagnose that its misdiagnostic incidence is quite high. The very-high-frequency (VHF) ultrasound is particularly relevant to the diagnosis of DF. Herein, we analyze the sonographic features and application value of VHF ultrasound in the diagnosis of DF.Methods: Clinical data from 153 patients with pathologically confirmed DF from January 2019 to December 2023 were retrospectively analyzed using high-resolution VHF ultrasound, including size, location, shape, edge, boundary, interior echo, blood supply and so on.Results: The VHF sonographic features of DF showed that the maximum diameter of the lesions was about 7.29 ± 2.85 mm (mean ± standard deviation). In addition, most lesions were located in the middle and lower part of dermis (49%), with ill-defined (84%) and irregular shape (51%), 19% of which were serrated. Forty-four percent of lesions were hypo-echoic and heterogeneous, and 8% were complicated with calcifications. Nineteen percent of lesions presented as thickened dermal epidermal junction. Dermatofibroma are mostly hypovascular on color Doppler ultrasound. Forty-three percent of lesions were detected with punctate dotted blood flow signals. The correlation analysis showed blood flow classification and maximum diameter were not relevant.Conclusion: The DF based on VHF ultrasonographic findings is characteristic, such as < 10mm, ill-defined, located in the dermis, thickened DEJ, serrated shape, punctute or no flow on Doppler, which provide crucial indicators for differential diagnosis, potentially reducing the rate of DF misdiagnosis.Keywords: dermatofibroma, very-high-frequency ultrasound, dermatosis

Xiaowen Han,1 Ruiling Xu,1 Yang Xia,2 Ying Liu,3 Shan Chen,3 Mingsong Shi,1 Zhiyan Zou,1 Yuanyuan Liang,1 Tingting Chen,1 Yufeng Tang,4 Wei Tang,3 Xiaoan Li,1,5 Liangxue Zhou2,6,7 1NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China; 2Department of Neurosurgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China; 3Institute of Materials, China Academy of Engineering Physics, Jiangyou, 621907, People’s Republic of China; 4Department of Neurology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China; 5Department of Gastroenterology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China; 6Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 7Department of Neurosurgery, the Fifth People’s Hospital of Ningxia, Shizuishan, Ningxia, 753000, People’s Republic of ChinaCorrespondence: Xiaoan Li; Liangxue Zhou, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China, Email lixiaoan@sc-mch.cn; liangxue_zhou@126.comPurpose: Skin radiation damage is a prevalent form of tissue injury encountered during radiotherapy, radiation accidents, and occupational exposure. The only clinically approved radioprotective agent, amifostine, is associated with numerous side effects, underscoring the urgent need for the development of safe and effective radioprotective agents. Natural products with reductive properties possess high antioxidant activity and biocompatibility, but their low bioavailability limits their radioprotective efficacy and clinical application. To address this, we utilized epigallocatechin gallate (EGCG) as a model compound and employed nanotechnology to enhance cellular uptake of natural compounds, thereby improving their free radical scavenging capabilities.Methods: EGCG nanoparticles (EGCG NPs) with robust intracellular reactive oxygen species (ROS) scavenging ability were prepared via self-assembly. The morphology, size distribution, and antioxidant capacity of EGCG NPs were characterized. Cytocompatibility, intracellular ROS levels and DNA damage, cell migration and immune response of EGCG NPs to macrophages were tested in vitro. The in vivo radiation protection and biocompatibility of EGCG NPs were assessed in murine model.Results: The EGCG NPs was successfully prepared and compared to free EGCG, EGCG NPs demonstrated better cellular uptake, significantly enhancing their biocompatibility, intracellular ROS scavenging capacity, and ability to mitigate DNA damage. Furthermore, EGCG NPs facilitated fibroblast proliferation and migration, while inhibiting the polarization of macrophages towards the M1 phenotype in vitro. In animal levels, EGCG NPs exhibited markedly improved radioprotective efficacy over free EGCG, effectively reducing skin edema and ulceration, alleviating pathological conditions such as interstitial edema, dermal fluid accumulation, and inflammatory infiltration, decreasing the duration of skin injury, and promoting wound healing.Conclusion: This work offers novel insights into the therapeutic application of EGCG NPs as a potential alternative for skin radioprotection and provides a powerful approach for developing radioprotective agents derived from natural products. Keywords: radiation-induced skin injury, nanoparticles, free radicals scavenging, radioprotection

Na Li,1,&ast; Xinyao Zhang,1,&ast; Yi Zheng,1 Qingchuan Liu,2 Sifang Niu,3 Yan Qin,4 Ying Zhang,5 Yan Liu,6 Jianli Wang7 1School of Mental Health, Jining Medical University, Jining, 272013, People’s Republic of China; 2School of Communication, East China Normal University, Shanghai, 200241, People’s Republic of China; 3School of Public Health, Binzhou Medical University, Yantai, 264003, People’s Republic of China; 4School of Public Health, Shandong First Medical University, Jinan, 250117, People’s Republic of China; 5School of Public Health, University of Sydney, Sydney, NSW, 2006, Australia; 6School of Public Health, Jining Medical University, Jining, 272013, People’s Republic of China; 7Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, B2N 5E3, Canada&ast;These authors contributed equally to this workCorrespondence: Jianli Wang, Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, B2N 5E3, Canada, Email jianli.wang@dal.ca Yan Liu, School of Public Health, Jining Medical University, Jining, 272013, People’s Republic of China, Email hakunaly@163.comBackground: Perfectionism is a pivotal factor in the etiology and prognosis of major depression. Nevertheless, there is a scarcity of longitudinal research examining the association between perfectionism and major depressive disorder (MDD). The objective of this study was to explore the impact of perfectionism on MDD among a cohort of first-year Chinese university students.Methods: This study employed a longitudinal design to investigate the relationship between perfectionism and MDD in a sample of first-year Chinese university students (n=8079). Socially prescribed perfectionism and almost perfectionism were measured using the Multidimensional Perfectionism Scale (MPS) and the Almost Perfect Scale-Revised (APS-R), while MDD was assessed using the Composite International Diagnostic Interview (CIDI-3.0). Random effects logistic regression modeling was utilized to estimate the associations between the variables.Results: The findings revealed that the incidence of MDD was 0.6%. Lifetime exposure to severe traumatic events (≥ 10) (OR=2.619, 95% CI: 1.502– 4.565) and almost perfectionism (OR=1.015, 95% CI: 1.004– 1.026) were identified as significant risk factors for MDD.Conclusion: It is evident that perfectionism is linked to an increased susceptibility to MDD. However, additional longitudinal studies focusing on university students are imperative to delve deeper into the influence of perfectionism on the initial manifestation of MDD.Keywords: freshmen, major depressive disorder, perfectionism, lifetime severe traumatic events

Qi Liu,1,2,&ast; Nan Nan,1,2,&ast; Wenfang Li,1,2 Mengwei Dong,1,2 Wei Pu,1,2 Yang Liu,1,2 Jie Zhao,3 Huiqin Hao1,2 1Basic Laboratory of Integrated Traditional Chinese and Western Medicine, Shanxi University of Chinese Medicine, Jinzhong, 030619, People’s Republic of China; 2Engineering Research Center of Cross Innovation for Chinese Traditional Medicine of Shanxi Province, Jinzhong, 03619, People’s Republic of China; 3Shanxi Provincial Key Laboratory of Classical Prescription Strengthening Yang, Taiyuan, 030013, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence:Huiqin Hao, Email hhq@sxtcm.edu.cnBackground: Rheumatoid arthritis (RA) is a synovial inflammation-associated autoimmune disease with secondary osteoporosis. Pain is the most important symptom of RA, and some patients with well-controlled inflammation may still experience pain.Purpose: To explore the relationship and dynamic changes between synovial inflammation and pain and bone destruction in collagen-induced arthritis (CIA) model rats, and to choose a better time window for drug treatment.Methods: The CIA model rats were constructed for 1, 2, 3, and 4-week groups. The changes were observed by joint swelling and behavioral assessment. The paw mechanical withdrawal threshold (PWT) was used for pain assessment. The micro-CT was used to assess joint injury and bone destruction. The biomechanics were performed to evaluate tension and compression test. The histological staining was used to observe ankle joint pathology. The immunohistochemical staining and Western blot were used to estimate the expression of calcitonin gene-related peptide (CGRP) and c-fos.Results: The results showed that the degree of joint swelling, synovial hyperplasia, and inflammatory response were alleviated to varying extents over time. However, there were no significant changes in bone destruction, osteoclasts, or the maximum load of compression and tension. It showed secondary osteoporosis from the first week of the CIA model with no significant changes during the course of the experiment. There was no significant improvement in the PWT, and the expression of CGRP and c-fos was significantly increased over time, indicating hyperalgesia aggravation. Additionally, the result showed that repeated open-field tests might reduce the total distance of spontaneous movement.Conclusion: The results suggested that the pain and joint inflammation might not be synchronized, possibly related to post-inflammatory hyperalgesia. CIA model could be used for the study of pain, also relatively stable and suitable for the study of RA with secondary osteoporosis.Keywords: collagen-induced arthritis rats, temporal changes, inflammation, pain, secondary osteoporosis

Zixiang Pang,&ast; Yangqin Ou,&ast; Jiawei Liang, Shengbin Huang, Jiayi Chen, Shengsheng Huang, Qian Wei, Yuzhen Liu, Hongyuan Qin, Yuanming Chen Department Orthopedics Ward 3 (Spine and Osteopathy Surgery), Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanming Chen, Department of Spinal Orthopedics, the Second Affiliated Hospital of Guangxi Medical University, No. 166, University East Road, Nanning, Guangxi, People’s Republic of China, Tel +86 13087712603, Email rkyygk@163.comObjective: The objective of this study aimed to investigate the risk factors for poor wound healing (PWH) after posterior lumbar spinal fusion. Currently, there is limited research on the application of machine learning in analyzing PWH after spinal surgery. Thus, our primary aim is to using machine learning identify these risk factors and construct a clinical risk prediction model.Methods: We retrospectively reviewed 2516 patients who underwent posterior lumbar spinal fusion at Guangxi Medical University’s Second Affiliated Hospital between August 2021 and August 2023. The data was divided into test and validation groups in a 7:3 ratio. In the test group, logistic regression analysis, support vector machine (SVM), random forest (RF), decision tree (DT), XGboost, Naïve Bayes (NB), k-Nearest Neighbor (KNN), and Multi-Layer Perceptron (MLP) were used to identify specific variables. The top six models from the eight machine learning models with the highest area under curve (AUC) values were selected and used to construct a dynamic nomograms model. Model performance was evaluated using receiver operating characteristic (ROC) and calibration curves. The model’s internal performance was then verified in the validation group using ROC and calibration curves.Results: Data from 2516 patients were collected, with 411 eligible cases selected. By combining logistic regression analysis with six machine learning algorithms, this study identified six predictors associated with PWH: subcutaneous lumbar spine index(SLSI), albumin, postoperative glucose, cerebrospinal fluid leakage(CSFL), neutrophil (NEU), and C-reactive protein(CRP). These predictors were used to develop a prediction model, visually represented through a nomogram. The AUC value in the test group was 0.981, and the C-index of the model was 0.986 (95% CI 0.966– 0.995), indicating excellent predictive capability. Calibration curve analysis showed good consistency between nomogram-predicted values and actual measurements.Conclusion: SLSI, albumin, postoperative glucose, CSFL, NEU and CRP were identified as significant risk factors for PWH after posterior lumbar spinal fusion. The developed prediction model exhibited excellent predictive accuracy and usefulness.Keywords: poor wound healing, posterior lumbar spinal fusion, machine learning, dynamic prediction model

Xudong Hu,1,2 Sihui Zhu,1,2 Xiao Yang,1,2 Menglei Shan,1,2 Jiawei Wang,1,2 Xin Da,1,2 Yongkang Gui,1,2 Yang Liu,1,2 Rui Yang,1,2 Guanghong Xu1,2 1Department of Anesthesiology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Key Laboratory of Anesthesia and Perioperative Medicine of Anhui Higher Education Institutes, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Guanghong Xu, Department of Anesthesiology, the First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui, 230022, People’s Republic of China, Tel/Fax +86055162922344, Email xuguanghong2004@163.comPurpose: Postoperative cognitive dysfunction (POCD) is a common postoperative complication. Studies have reported that lymphocyte-to-monocyte ratio (LMR) was a predictor of many diseases associated with inflammation. However, further examination of the relationship between preoperative LMR and POCD is needed. We aimed to investigate the association between POCD and preoperative LMR levels to examine the potential of LMR to predict POCD.Patients and Methods: This was a prospective cohort study that included patients who underwent elective major abdominal surgery at our hospital between January 2019 and January 2022. Multivariate logistic regression analysis was used to analyze the effects of preoperative LMR on POCD development. The optimal threshold of preoperative LMR for predicting POCD was determined by receiver operating characteristic (ROC) approach. A subgroup analysis was performed according to age, sex, type of surgery and hypertension.Results: Of 964 patients, 362 (37.6%) developed POCD. The preoperative LMR level in the Non-POCD group was higher than that in the POCD group. According to the ROC curve, a cutoff value of 3.758 of the preoperative LMR level could be used to predict POCD occurrence and the area under the curve (AUC) was 0.747 (95% CI: 0.715– 0.779, P < 0.001). The results of the subgroup analyses were consistent with the primary ones, and no heterogeneity was observed in the subgroup analyses (P for interaction > 0.05).Conclusion: LMR was significantly associated with the occurrence of POCD after major abdominal surgery. Preoperative low LMR levels can be used to identify patients who may be at high risk of POCD.Keywords: postoperative cognitive dysfunction, lymphocyte-to-monocyte ratio, abdominal surgery, systemic inflammation

Yingjie Hua,1,&ast; Yongkang Geng,2,&ast; Surui Liu,3 Shuiwei Xia,4 Yan Liu,3 Sufang Cheng,4 Chunmiao Chen,4 Chunying Pang,2 Zhongwei Zhao,1 Bo Peng,3 Yakang Dai,3 Jiansong Ji,4 Dan Wu1 1Department of Pain Medicine, Zhejiang Key Laboratory of Imaging and Interventional Medicine. The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang Province, People’s Republic of China; 2School of Life Science and Technology, Changchun University of Science and Technology, Changchun, Jilin Province, People’s Republic of China; 3Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu Province, People’s Republic of China; 4Department of Radiology, Zhejiang Key Laboratory of Imaging and Interventional Medicine. The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiansong Ji; Dan Wu, Email jjstcty@wmu.edu.cn; 215066083@qq.comObjective: This study investigates the differences in brain functional activity and connectivity patterns between Cancer Pain (CP) patients and Healthy Controls (HCs) using resting-state functional magnetic resonance imaging (rs-fMRI) to identify potential neuroimaging biomarkers.Methods: This study collected rs-fMRI data from 25 CP patients and 25 hCs, processed the functional MRI images, and calculated metrics such as amplitude of low-frequency fluctuation (ALFF), Regional Homogeneity (ReHo), and FC. Through statistical analysis, differences in brain functional activity and connectivity between the cancer pain group and the healthy control group were investigated, followed by machine learning classification.Results: The results showed that compared to the normal group, reductions in the ALFF were primarily observed in the bilateral inferior temporal gyrus; ReHo increased in the right middle temporal gyrus and decreased in the left cerebellum Crus2. Using the statistically different brain areas as seed points to construct FC networks and performing statistical analysis, it was found that the regions with decreased FC connection strength between the cancer pain group and the normal group were mainly in the prefrontal cortex (PFC), the postcentral gyrus of the parietal lobe, and the cerebellum. Statistical results indicated that there was no significant correlation between pain scores (Numeric Rating Scale, NRS) and neuroimaging metrics. According to the machine learning classification, the FC features of the right precentral gyrus achieved higher diagnostic efficacy (AUC = 0.804) compared to ALFF and ReHo in distinguishing between CP patients and HCs.Conclusion: Brain activity and FC in CP patients show abnormalities in regions such as the inferior temporal gyrus, middle temporal gyrus, prefrontal cortex, parietal lobe, and cerebellum. These areas may be interconnected through neural networks and jointly participate in functions related to pain perception, emotion regulation, cognitive processing, and motor control. However, the precise connections and mechanisms of action require further research.Keywords: cancer pain, resting-state fMRI, low-frequency fluctuations, regional homogeneity, functional connectivity

Wensen Pi, Yang Liu, Haidan Chen, Hongwei Zhao Department of Spine Surgery of Yichang Central People’s Hospital, First Clinical Medical College of China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of ChinaCorrespondence: Hongwei Zhao; Haidan Chen, Department of Spine Surgery of Yichang Central People’s Hospital, First Clinical Medical College of China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of China, Email ycguke@sina.com; wenquanchd@sina.comAbstract: Tuberculous spondylitis following percutaneous vertebroplasty or kyphoplasty is rare. In this, we report a rare case of tuberculous spondylitis diagnosed after percutaneous vertebroplasty (PVP). A 69-year-old female sought came to our department with a history of chest and back pain from the last two months accompanied by weakness in both lower limbs. The patient underwent two vertebroplasty procedures at a local hospital within two years for compression fractures of the lumbar and thoracic spine. Due to continuous lower back pain following PVP surgery, along with the worsening back pain weakness in both lower limbs over the past 2 months, the patient presented to our hospital for the treatment. Radiological imaging showed long bone destruction in the L1, L2, and T12 vertebrae, accompanied by the formation of numerous paraspinal abscesses. The serum T-SPOT test yielded a positive result. A sample was taken from a paravertebral abscess for TB DNA testing (GeneXpert MTB/RIF assay) under the guidance of CT, which demonstrated the patient was infected with a non-drug-resistant strain of TB. The patient underwent surgical treatment via a combined anterior and posterior approach. The histological examination of the excised tissue revealed evidence of tuberculosis, characterized by granulomatous inflammation and sheet necrosis. After taking anti tuberculosis drugs for 12 months, the patient recovered without any sequelae. Spinal tuberculosis and osteoporotic vertebral compression fractures are similar in clinical and radiological aspects. Spinal surgeons should consider the entity of this disease to avoid misdiagnosis or complications. After diagnosis of spinal tuberculosis after vertebral augmentation surgery, early surgical intervention and anti-tuberculosis treatment should be carried out immediately.Keywords: Tuberculous spondylitis, vertebroplasty

Zhiwei Long,1,2,&ast; Qiyuan Zeng,2,&ast; Yonger Ou,1,&ast; Yuelin Liu,2,3 Jieying Hu,1 Ya Wang,1,3 Yan Wang1 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Clinical Medicine, Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Department of Critical Care Medicine, the First Affiliated Hospital of Guangzhou Medical University; Guangzhou Institute of Respiratory and Health; Medical Center for Respiratory Medicine; State Key Laboratory of Respiratory Disease, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Wang; Ya Wang, Email 345406739@qq.com; wangya811710@163.comPurpose: Elevated red blood cell distribution width (RDW) and decreased hematocrit (HCT) levels are associated with poor prognosis in chronic obstructive pulmonary disease (COPD) patients, but their significance in intensive care unit (ICU) patients with acute exacerbation of COPD (AECOPD) remains uncertain. The RDW/HCT ratio may offer a more comprehensive assessment compared to individual markers, potentially enhancing prognostic accuracy. Furthermore, the utility of RDW/HCT in improving traditional ICU scoring systems remains unexplored.Patients and Methods: The optimal RDW/HCT ratio cutoff was identified via ROC curve analysis, guiding classification into high and low ratio groups. Univariate and multivariate logistic regression analyses, Kaplan-Meier survival curves, and propensity score matching (PSM) were performed to evaluate the association between RDW/HCT ratio and 28-day all-cause mortality. The predictive value of RDW/HCT ratio compared to traditional ICU scoring systems was assessed using the area under the curve (AUC). Additionally, the eICU database was utilized to validate the robustness of the association between RDW/HCT and mortality in patients with AECOPD.Results: 624 patients were included, with 361 in the low RDW/HCT ratio group and 263 in the high ratio group. PSM yielded 145 matched pairs of patients with balanced baseline characteristics. Multivariate logistic regression analysis revealed that patients with RDW/HCT ratio ≥ 0.473 had significantly higher 28-day all-cause mortality compared to those with RDW/HCT ratio < 0.473 (p < 0.001). Combining RDW/HCT ratio with SOFA score improved the diagnostic accuracy significantly (p=0.029).Conclusion: The RDW/HCT ratio is an independent predictor of 28-day all-cause mortality in AECOPD patients in the ICU. It can be used for a preliminary assessment before a systematic evaluation of the patient, indicating its potential value in early assessment of disease severity. In a comprehensive evaluation, combining the RDW/HCT ratio with the SOFA score can further enhance predictive accuracy.Keywords: red blood cell distribution width, hematocrit, chronic obstructive pulmonary disease, intensive care unit, prognosis

Xinyu Zhao,1 Yang Wang,2,3 Xiaoyi Li,1 Peiqun Hu,2 Xiong-Fei Pan,4– 6 Benxiang He,7 Yunlu Liu,8 Yushi Hu,2 Tianmin Zhu9 1School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 2School of Sports Medicine and Health, Chengdu Sport University, Chengdu, Sichuan, People’s Republic of China; 3Postdoctoral Workstation, Affiliated Sport Hospital of Chengdu Sport University, Chengdu, Sichuan, People’s Republic of China; 4Section of Epidemiology and Population Health & Department of Gynecology and Obstetrics, Ministry of Education Key Laboratory of Birth Defects and Related Diseases of Women and Children & National Medical Products Administration Key Laboratory for Technical Research on Drug Products in vitro and in vivo Correlation, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 5West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 6Shuangliu Institute of Women’s and Children’s Health, Shuangliu Maternal and Child Health Hospital, Chengdu, Sichuan, People’s Republic of China; 7Sichuan Academy of Chinese Medicine Science, Chengdu, Sichuan, People’s Republic of China; 8Institute of Laboratory Animal Sciences, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 9School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Tianmin Zhu, School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China, Email tianminzhu@cdutcm.edu.cn Yushi Hu, School of Sports Medicine and Health, Chengdu Sport University, Chengdu, Sichuan, People’s Republic of China, Email huyushi@cdsu.edu.cnObjective: This study aims to evaluate the efficacy of acupuncture as an adjunct to lifestyle interventions on weight loss in simple obesity.Methods: Potentially eligible studies that assessed anthropometric outcomes as well as glucose and lipid metabolism following acupuncture combined with lifestyle interventions in simple obesity patients were searched from eight databases from inception to October 2023. All analyses were performed using the Review Manager software v5.4 and Stata software v17.0.Results: Herein, 25 randomized controlled trials (RCTs) involving 2018 patients were included. Generally, acupuncture combined with lifestyle interventions outperformed lifestyle interventions alone in terms of body weight (MD = − 4.73, 95% CI [− 6.32, − 3.13], p < 0.00001), body mass index (BMI) (MD = − 2.11, 95% CI [− 2.75, − 1.48], p < 0.00001), waist circumference (WC) (MD = − 4.96, 95% CI [− 6.89, − 3.03], p < 0.00001), body fat percentage (BF %) (MD = − 2.61, 95% CI [− 4,51, − 0.71], p = 0.007), fasting plasma glucose (FPG) (SMD = − 0.66, 95% CI [− 1.02, − 0.31], p = 0.0002), fasting serum insulin (FINS) (SMD = − 1.12, 95% CI [− 1.44, − 0.81], p < 0.00001), homeostasis model assessment-insulin resistance (HOMA-IR) (MD = − 1.22, 95% CI [− 1.50, − 0.94], p < 0.00001), total cholesterol (TC) (SMD = − 1.14, 95% CI [− 1.83, − 0.45], p = 0.001), triglyceride (TG) (SMD = − 1.31, 95% CI [− 2.07, − 0.56], p = 0.0006), and low-density lipoprotein cholesterol (LDL-C) (SMD = − 1.81, 95% CI [− 3.11, − 0.51], p = 0.006). Subgroup analysis based on three subgroup variables (types of acupuncture and lifestyle interventions as well as treatment durations) could partially explain the heterogeneity of the results.Conclusion: Acupuncture demonstrated an enhancing effect on the benefits of lifestyle interventions for weight loss in patients with simple obesity, including reducing body weight and improving glucose and lipid metabolism. This finding suggests its potential value as a complementary therapy alongside lifestyle interventions in a clinical setting. However, further validation with rigorously designed and high-quality RCTs is still needed in the future.Keywords: obesity, acupuncture, acupuncture therapy, meta-analysis, systematic review

Yunfeng Jia,1 Yayi Liu,1 Yiming Zuo,1 Junping Zhang,1 Yanyang Li,2,3 Xuezheng Liu,1 Shichao Lv1 1Department of Geriatrics, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine (National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion), Tianjin, 300381, People’s Republic of China; 2Department of Integrated Traditional and Western Medicine, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People’s Republic of China; 3Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of ChinaCorrespondence: Shichao Lv; Xuezheng Liu, Department of Geriatrics, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, No. 88 Changling Street, Xiqing District, Tianjin, 300193, People’s Republic of China, Email dr_lv@foxmail.com; drhare1975@163.comAbstract: Heart failure (HF) represents a serious manifestation or advanced stage of various cardiac diseases. HF continues to impose a significant global disease burden, characterized by high rates of hospitalization and fatality. Furthermore, the pathogenesis and pathophysiological processes underlying HF remain incompletely understood, complicating its prevention and treatment strategies. One significant pathophysiological mechanism associated with HF is the systemic inflammatory response. PANoptosis, a novel mode of inflammatory cell death, has been extensively studied in the context of infectious diseases, neurodegenerative disorders, cancers, and other inflammatory conditions. Recent investigations have revealed that PANoptosis-related genes are markedly dysregulated in HF specimens. Consequently, the PANoptosis-mediated inflammatory response may represent a potential mechanism and therapeutic target for HF. This paper conducts a comprehensive analysis of the molecular pathways that drive PANoptosis. We discuss its role and potential therapeutic targets in HF, thereby providing valuable insights for clinical treatment and the development of novel therapies.Keywords: PANoptosis, pyroptosis, apoptosis, necroptosis, cell death, heart failure

Pilong Shi,1,&ast; Yuetong Sha,1,&ast; Xinran Wang,1,&ast; Tao Yang,1 Jiawei Wu,1 Jiajun Zhou,1 Kai Liu,1 Xue Guan,2 Song Wang,1 Yongsheng Liu,1 Jingquan Gao,3 Hongli Sun,1 Tao Ban,1 Yonggang Cao1 1Department of Pharmacology, Harbin Medical University, Heilongjiang, 163319, People’s Republic of China; 2Morphological Experiment Center, Harbin Medical University, Heilongjiang, 163319, People’s Republic of China; 3Department of Nursing, School of Medicine, Lishui University, Lishui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonggang Cao; Hongli Sun, Email 437343482@qq.com; sunhongli@hmudq.edu.cnPurpose: Myocardial ischemia-reperfusion injury (MI/RI) is associated with increased oxidative damage and mitochondrial dysfunction, resulting in an elevated risk of mortality. MI/RI may be alleviated by protecting cardiomyocytes from oxidative stress. Lutein, which belongs to a class of carotenoids, has proven to be effective in cardiovascular disease treatment due to its remarkable antioxidant properties, but its application is limited due to its poor stability and low bioavailability in vivo.Methods: In this study, a delivery system was developed based on distearoyl phosphatidyl ethanolamine (DSPE)-thiol-ketone (TK)-PEG2K (polyethylene glycol 2000) (abbreviated as DTP) and PCM-SH (CWLSEAGPVVTVRALRGTGSW) to deliver lutein (abbreviated as lutein@DTPP) to damaged myocardium. First, lutein, lutein@DTP, or lutein@DTPP were injected through the tail vein once a day for 3 days and then MI/RI model rats were established by exposing rats to ischemia for 45 min and reperfusion for 6 h. We employed a range of experimental techniques including qRT-PCR, Western blotting, transmission electron microscopy, immunohistochemistry, immunofluorescence, flow cytometry, immunoprecipitation, molecular docking, and molecular dynamics simulations.Results: Lutein@DTPP exhibited good myocardial targeting and ROS-responsive release. Our data suggested that lutein@DTPP effectively suppresses ferroptosis in cardiomyocytes. Mechanistically, we observed an upregulation of mouse double minute-2 (MDM2) in the hearts of MI/RI models and cardiomyocytes exposed to hypoxia/reoxygenation (H/R) conditions. In addition, NADH-ubiquinone oxidoreductase 75 kDa Fe-S protein 1 (NDUFS1) translocation from the cytosol to the mitochondria was inhibited by MDM2 upregulation. Notably, no significant variation in the total NDUFS1 expression was observed in H/R-exposed cardiomyocytes following treatment with siMDM2. Further study indicated that lutein facilitates the translocation of NDUFS1 from the cytosol to mitochondria by directly binding and sequestering MDM2, thereby improving mitochondrial function and inhibiting ferroptosis.Conclusion: Lutein@DTPP promoted the mitochondrial translocation of NDUFS1 to restore mitochondrial function and inhibited the ferroptosis of cardiomyocytes by directly binding and sequestering MDM2. Keywords: myocardial ischemia-reperfusion injury, lutein, ROS, MDM2, NDUFS1, ferroptosis

Tianjie Zhang,1 Yan Liu,1 Dongwei Xu,2 Rui Dong,1 Ye Song1 1Department of Ultrasonography, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318,People’s Republic of China; 2Department of Critical Care Medicine, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Ye Song, Email songy_18@sumhs.edu.cnBackground: This study aims to evaluate the predictive value of bedside ultrasound evaluation of diaphragmatic dynamics in determining successful extubation outcomes for patients eligible for weaning.Methods: This prospective observational study was conducted on patients who were mechanically ventilated and ready for weaning during the spontaneous breathing trial (SBT). The diaphragm contraction and motion-related parameters of patients such as end inspiratory diaphragm thickness (DT-insp), end respiratory diaphragm thickness (DT-exp), diaphragm thickening fraction (DTF), diaphragmatic thickening fraction rapid shallow breathing index (DTF-RSBI), diaphragmatic excursion (DE), diaphragmatic excursion rapid shallow breathing index (DE-RSBI) were recorded and the association with failure in ventilatory extubation was analyzed. A receiver operating characteristic (ROC) curve was conducted to analyze the prediction of successful weaning.Results: Out of 95 patients, 14 (14.74%) died, and 68 (71.58%) were successfully extubated. There were significant differences between the two groups in all parameters except DT-exp. The results indicated that duration of mechanical ventilation (OR = 0.850, 95% CI: 0.770– 0.938, P = 0.001), DTF (OR = 1.214, 95% CI: 1.108– 1.330, P = 0.000), DTF-RSBI (OR = 0.917, 95% CI: 0.880– 0.954, P = 0.000), DE (OR = 127.02, 95% CI: 15.004– 1075.291, P = 0.000), DE-RSBI (OR = 0.752, 95% CI: 0.657– 0.861, P = 0.000) had predictive value for weaning. DTF and DE had a high sensitivity of 91.18%, 100%, respectively. Whereas, duration of mechanical ventilation, DTF-RSBI, DE-RSBI showed a high specificity of 81.48,85.19%, 81.48%. Considering all the above factors, the sensitivity was 88.24% and the specificity was 88.89%.Conclusion: Bedside ultrasound assessment of diaphragmatic parameters enables the detection of diaphragmatic dysfunction, thus proving valuable in predicting extubation success and facilitating a favorable weaning outcome.Keywords: diaphragmatic dynamics, bedside ultrasound, extubation, intensive care unit

Jingkai Di,1,2,&ast; Liying Song,2,3,&ast; Yaru Liu,2,4,&ast; Zhibo Zhang,1,2 Yawen Wu,2 Tingting Chen,2,5 Chuan Xiang1 1The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Medical University, Taiyuan, People’s Republic of China; 3The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4The Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 5The Fifth Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuan Xiang, The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China, Tel +86 15903410351, Email chuanxiang@sxmu.edu.cnPurpose: Despite the association between peripheral blood inflammatory biomarkers and a range of inflammatory diseases, the role of these biomarkers in osteoarthritis (OA) progression remains unclear. Additionally, whether alterations in these inflammatory markers impact the prognosis of OA patients remains an understudied area. The aim of our study was to investigate the specific associations between peripheral blood inflammatory markers and OA progression and OA-related mortality.Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) database from 1999 through 2018. The primary outcomes were all-cause mortality, cardiac mortality, and renal disease mortality, with information on the corresponding mortality rates for each participant obtained through association with the National Death Index (NDI). Multivariate logistic regression models were used to examine the relationship between peripheral blood lymphocyte counts and OA, and restricted cubic spline (RCS) analysis was utilized to assess whether there was a nonlinear relationship with OA and mortality of OA patients. Interaction and stratified analyses were employed to explore the association between peripheral blood leukocyte counts and OA.Results: This study included 1077 OA patients and 21,612 non-OA participants. In model 3 fully adjusted for covariates, eosinophil-to-lymphocyte ratio (ELR) and eosinophil (EOS) were positive risk factors promoting the development of OA (OR = 3.26, 95% CI: 1.49– 7.14; OR = 1.79, 95% CI: 1.12– 2.88). In stratified models for age, sex, BMI, smoking status, and alcohol consumption, the associations of ELR and EOS with OA were significantly different. RCS curves showed a J-shaped relationship between ELR and EOS and all-cause mortality in patients with OA. ELR was also found to significantly up-regulate cardiac mortality and renal mortality in patients with OA (OR = 3.92, 95% CI: 1.68– 9.14; OR = 22.55, 95% CI: 6.55– 77.70), while EOS was only significantly positively correlation (OR = 3.68, 95% CI: 1.94– 7.01).Conclusion: A significant relationship was found between ELR, EOS and OA. In addition, ELR and EOS were identified as potential predictors of mortality from different causes in patients with OA.Keywords: eosinophil to lymphocyte ratio, osteoarthritis, eosinophil, all-cause mortality

Chengran Wang,&ast; Xiaoqing Zhao,&ast; Keyan Wang, Huixin Liang, Shuhan Chen, Yajie Liu, Hua Yao, Jinlan Jiang Department of Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Yao; Jinlan Jiang, Department of Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China, Tel\Fax +86-13596102816, Email yao_hua@jlu.edu.cn; jiangjinlan@jlu.edu.cnAbstract: Disseminated intravascular coagulation (DIC) is an acquired disorder characterized by systemic activation of blood coagulation, which can arise from various causes. Owing to its abrupt onset, rapid progression, and high mortality rate, DIC presents a major clinical challenge. Anticoagulant drugs, such as heparin or low-molecular-weight heparin, are the current gold standard of treatment; however, these interventions pose considerable bleeding risks. Thus, safer and more effective therapeutic strategies are urgently required. Owing to their strong anti-inflammatory and tissue repair capabilities, mesenchymal stem cell-derived exosomes (MSC-Exos) have gained considerable attention as novel therapeutic options for numerous disorders, including DIC. Their stability in diverse pathological states highlights their potential as promising candidates for DIC therapy. This review presents the latest insights on the pathogenesis of DIC and anti-inflammatory and anticoagulant properties of MSC-Exos. We aimed to elucidate the potential mechanisms by which MSC-Exos influence DIC pathogenesis. We speculate that MSC-Exos offer a multifaceted approach to DIC treatment by attenuating neutrophil extracellular trap formation, modulating M1/M2 macrophage polarization, altering Nrf2/NF-κB signalling pathway to downregulate pro-inflammatory factors, and correcting imbalances in the coagulation-fibrinolysis system through anticoagulant routes. This suggests that MSC-Exos are a potential paradigm in DIC therapy, offering novel targets and treatment modalities for DIC management. Keywords: disseminated intravascular coagulation, mesenchymal stem cell-derived exosomes, anticoagulant therapy, neutrophil extracellular traps, macrophage polarization

Jiamin Long,1,2,&ast; Jiali Chen,3,&ast; Yue Yuan,4,&ast; Shaozhen Yang,5,&ast; Xinya Xie,1,2 Xuelian Wu,1,2 Yuan Liu,1,2 Jinpeng Guo,2 Yong Chen,1,2 Changjun Wang,1,2 Xiong Liu2 1School of Public Health, China Medical University, Shenyang, 110122, People’s Republic of China; 2Chinese PLA Center for Disease Control and Prevention, Beijing, 100071, People’s Republic of China; 3School of Medicine, NanKai University, Tianjin, 300071, People’s Republic of China; 4Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China; 5School of Basic Medical Sciences, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiong Liu; Changjun Wang, Chinese PLA Center for Disease Control and Prevention, Beijing, 100071, People’s Republic of China, Email liuxiong714@163.com; science2008@hotmail.comBackground: Klebsiella michiganensis is an emerging human pathogen that causes nosocomial infections. Its prevalence and spread in the environment should not be ignored. This study identified and characterized Klebsiella michiganensis co-harboring blaKPC-2 and TmexCD2-ToprJ2 in hospital wastewater samples.Methods: Twelve K. michiganensis strains were isolated from wastewater samples collected at a tertiary hospital in Beijing, China. The genomic characteristics of K. michiganensis strains were analyzed using whole-genome sequences, providing information on the comparison between the genome of K. michiganensis strains and the reference genome, antibiotic resistance genes (ARGs), virulence genes, secretion systems, and mobile genetic elements (plasmids, insertion sequences [ISs], and prophages).Results: Genome analysis showed that the twelve multi-drug resistant (MDR) strains carried a variety of ARGs and virulence genes, as well as four macromolecular secretion systems (T1SS, T2SS, T5aSS, T5bSS, and T4aP). The genetic environments of both the TmexCD2-ToprJ2 gene cluster and blaKPC-2 gene contained ISs. The plasmids carrying TmexCD2-ToprJ2 gene cluster of nine strains in clade 1 and two strains in clade 2 were annotated as IncR plasmid and rep_cluster_1254 type, respectively. The plasmids carrying blaKPC-2 in 10 strains in clade 1 were identified as IncU, and the plasmids carrying blaKPC-2 in the k11 and k12 strains in clade 2 were IncU and IncX6. The phylogenetic tree and heatmap revealed that the secretion system of type VI (T6SSi) existed in 10 strains in clade 1, and Type IV (T4SS) only existed in the k11 strain in clade 2. In addition, K. michiganensis strains carried 13 plasmids, 14 ISs, and 138 prophages.Conclusion: In this study, the whole genome sequencing demonstrated the diversity of K. michiganensis genome despite 12 K. michiganensis strains from a hospital wastewater, which lays the foundation for further genetic research and drug resistance gene transmission.Keywords: Klebsiella michiganensis, hospital wastewater, whole-genome sequencing, blaKPC-2, TmexCD2-ToprJ2

Teng-Yue Zhao,1,2 Bing-Jie Wang,3 Jiang Liu,1 Chu Liu,1 Ji-Qiang Bu,1 Yu Liu,1 Fang Yan,1 Wen-Li Zhang,1 Zi-Ying Chen,1 Yu-Ming Wu2 1Department of Cardiac Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 2Department of Physiology, Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 3Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Zi-Ying Chen, Department of Cardiac Surgery, The Second Hospital of Hebei Medical University, No. 215 of Heping West Road, Xinhua District, Shijiazhuang, 050000, People’s Republic of China, Tel +86 15803210520, Email ziyingchenorg@126.com Yu-Ming Wu, Department of Physiology, Hebei Medical University, No. 361 of Zhong Shan East Road, Shijiazhuang, 050017, People’s Republic of China, Tel +8631186261288, Email wuym@hebmu.edu.cnObjective: The employment of the no-touch technique in harvesting the great saphenous vein (GSV) for coronary artery bypass grafting has been associated with a significant improvement in clinical patency rates. Despite these advantages, such grafts may predispose patients to complications in the lower limbs. This study endeavors to evaluate the incidence of complications in the lower extremities by deploying an enhanced protocol for the no-touch harvesting technique.Methods: The historical control group in this study included patients who underwent coronary artery bypass grafting (CABG) with the no-touch technique for GSV harvesting at our institution from August 2018 to April 2020, in compliance with ethical standards. The intervention group consisted of patients who received CABG and were subjected to an optimized no-touch technique for GSV harvesting from May 2020 to June 2022. Technical modifications were applied to reduce lower limb complications, including limited use of electrocautery, minimization of extravascular tissue preservation, relaxation of postoperative elastic compression bandages, and elevation of the lower extremities. These measures aimed to decrease the incidence of postoperative lower limb complications, such as pain, numbness, edema, exudation, and delayed healing. The occurrences of postoperative complications were meticulously documented, compared, and analyzed between the two groups.Results: The adoption of the optimized no-touch technique resulted in a significant decrease in the incidence of postoperative lower extremity incisional complications among patients subjected to off-pump CABG (p < 0.05).Conclusion: The results of this study substantiate that the application of an optimized no-touch technique to harvest the GSV significantly diminishes the incidence of postoperative lower limb complications in patients receiving CABG. These results highlight the importance of adopting and integrating this optimized technique into clinical protocols, emphasizing its critical role in advancing patient care outcomes.Keywords: historical controlled study, lower limb complications, no-touch great saphenous vein, off-pump coronary artery bypass grafting, propensity score matching

Quanfeng Liao,1 Yu Feng,2 Jin Deng,1 Weili Zhang,1 Siying Wu,1 Ya Liu,1 Yi Xie,1 Mei Kang1 1Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Mei Kang, Email kangmei@sina.comObjective: Ceftazidime-avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor with activity against carbapenem-resistant Klebsiella pneumoniae (CRKP) that produce Klebsiella pneumoniae carbapenemase (KPC). In this study, we report the first cases of CZA resistance to develop during treatment of CRKP infections and identify the resistance mechanism.Methods: APB/EDTA and NG-Test CARBA5 were used to detect the production of carbapenemase, whole-genome sequencing (WGS) and conjugation experiment were used to identify potential resistance mechanisms of CZA-susceptible (HX1032) and -resistant (HX1192) K. pneumoniae isolates.Results: HX1192 K. pneumoniae was not recognized by APB/EDTA and NG-Test CARBA5 phenotypic assays, WGS revealed it carrying a novel KPC variant, KPC-179, molecular analysis highlighted a G394A mutation, and an ATC insertion at 543 in the blaKPC-2 gene, resulting in an A133T substitution and insertion of the amino acid S at Ambler position 183 in the protein sequence. Remarkably, this mutation restored susceptibility of imipenem (MIC = 0.25 mg/L).Conclusion: Our study highlights the importance of monitoring susceptibility during CZA treatment and accurately detecting KPC variants.Keywords: CZA resistance, carbapenem-resistant, Klebsiella pneumoniae, KPC variant, phenotypic test

Xunxun Feng,1,2 Yang Liu,1 Jiaqi Yang,1 Zhiming Zhou,1 Shiwei Yang,1 Yujie Zhou,1,&ast; Qianyun Guo1,&ast; 1Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Beijing Institute of Heart Lung and Blood Vessel Disease, Clinical Center for Coronary Heart Disease, Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Medicine, Division of Cardiology, University of California, Los Angeles, CA, USA&ast;These authors contributed equally to this workCorrespondence: Yujie Zhou; Qianyun Guo, Email azzyj12@163.com; gqydyx3000@163.comObjective: This research aimed to address the critical need for effective prognostic tools in patients with acute coronary syndrome (ACS) and type 2 diabetes mellitus (T2DM) undergoing percutaneous coronary intervention (PCI) by exploring the potential significance of integrating estimated glucose disposal rate (eGDR) and neutrophil-to-lymphocyte ratio (NLR).Methods: Major adverse cardiovascular and cerebrovascular events (MACCE) were the primary endpoint. Log rank test was conducted to compare the Kaplan–Meier curves across the overall follow-up period, and multivariate Cox regression was used to investigate the association between the eGDR/NLR and MACCE.Results: One hundred fifty-four patients (9.5%) experienced MACCE including 15 cardiac deaths, 97 nonfatal MI, 120 TVR, and 10 strokes. Patients were distributed into low and high eGDR/NLR groups (lower eGDR [eGDR-L] group, higher eGDR [eGDR-H] group, lower NLR [NLR-L] group, and higher NLR [NLR-H] group) based on the median value of eGDR and NLR, further divided into four groups: eGDR-L + NLR-L, eGDR-H + NLR-L, eGDR-L + NLR-H, and eGDR-H + NLR-H. eGDR-L + NLR-H group exhibited significantly higher risks of MACCE (17.4%), compared to another three groups. An independent correlation between eGDR/NLR and MACCE was demonstrated by Cox regression analysis, establishing if the eGDR and NLR was treated as a continuous or categorical variable. Compared to eGDR-H + NLR-L group, patients in eGDR-L + NLR-H group had the uppermost MACCE risk (HR: 5.201; 95% CI 2.764– 7.786; P < 0.001). A linear relationship between eGDR/ NLR and MACCE was showed by restricted cubic spline curves. Incorporating the eGDR and NLR toward the baseline risk model developed the precision of forecasting MACCE (baseline risk model-AUC: 0.611 vs baseline risk model + eGDR + NLR-AUC: 0.695, P < 0.001).Conclusion: Combining eGDR with NLR can be utilized to forecast long-term MACCE and substantially improve the accuracy of risk stratification in ACS patients with T2DM following PCI.Keywords: estimated glucose disposal rate, neutrophil-to-lymphocyte ratio, type 2 diabetes mellitus, acute coronary syndrome, percutaneous coronary intervention

Min Li,1,2 Song Zhao,2 Yan Liu,1 Qian Wang,2 Yongzhe Chen,2 Yaru Zhou1 1Department of Endocrinology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China; 2Department of Nephrology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of ChinaCorrespondence: Yaru Zhou, Department of Endocrinology, The Third Hospital of Hebei Medical University, Shijiazhuang, Ziqiang Road 139, Hebei, 050051, People’s Republic of China, Tel +86-0311-88603031, Email zyrydsy@hebmu.edu.cnBackground: Diabetes kidney disease (DKD) is a common complication of diabetes and is currently considered the primary cause of end-stage renal disease. Ferroptosis has been found to participate in the development of DKD. However, no ferroptosis-related markers have been evaluated in human DKD samples. This study aimed to examine the ferroptosis-related pathological alterations in DKD samples.Methods: This study enrolled patients with DKD at the Third Hospital of Hebei Medical University between January 2018 and December 2022, of whom 30 were diagnosed with DKD and 10 with non-DKD (CON). Clinical data of patients were collected, and hematoxylin-eosin staining (H&E), PASM, and immunohistochemical staining were performed to evaluate pathological changes and the expression of ferroptosis-related proteins, including GPX4, ACSL4, Nrf2, TfR1, FTH, and FTL.Results: Compared with the CON group, patients with DKD exhibited significantly elevated serum creatinine levels and reduced eGFR (P < 0.05). Iron content and the expression of the ferroptosis-related protein ACSL4 were significantly increased, while the expression of Nrf2 was significantly decreased in the renal tissues of patients with DKD (P all < 0.05). There were no differences in the expression of GPX4, TfR1, FTH, or FTL between the two groups. Nrf2 and ACSL4 expression were influential factors in the occurrence of DKD and both exhibited diagnostic value for DKD. Nrf2 was a protective factor (OR, < 1), whereas ACSL4 was a risk factor (OR, > 1).Conclusion: Ferroptosis-promoting gene profile was identified in DKD renal samples, indicating that ferroptosis may participate in the pathogenesis of DKD. The expression levels of Nrf2 and ASCL4 in the kidneys are related to the severity and progression of DKD.Keywords: diabetes kidney disease, ferroptosis, iron overload, lipid peroxidation

Wenhao Chen,1 Yuanliang Liu,2 Xunwei Deng,3 Bin Li,1 Hao Wang,1 Guoliang Wei,1 Kehui Chen,1 Shen Wang1 1Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 2Department of Computer Tomography, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 3Research Experimental Center, Meizhou People’s Hospital, Meizhou, People’s Republic of ChinaCorrespondence: Wenhao Chen, Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou, People’s Republic of China, Email 18319255493@163.comObjective: Cytochrome P450 2C19 (CYP2C19) is a major enzyme involved in the biotransformation and metabolism of various substances. Loss-of-function of the CYP2C19 gene represents downregulation of CYP2C19 enzyme indication limited or no enzymatic function, which may be, in turn, associated with some disease susceptibility. The relationship between CYP2C19 polymorphisms and susceptibility to premature coronary artery disease (PCAD) is not fully understood. This study aimed to assess this relationship.Methods: This study included 635 PCAD patients, and 548 age-matched non-CAD individuals as controls, from November 2019 to August 2023. The CYP2C19 rs4244285 (681G > A, &ast;2) and rs4986893 (636G > A, &ast;3) were genotyped, and the distribution of CYP2C19 polymorphisms between patients and controls and the relationship between CYP2C19 polymorphisms and PCAD risk were analyzed.Results: A total of 442 (37.4%), 543 (45.9%), and 198 (16.7%) individuals had CYP2C19 extensive metabolizer (EM) (&ast;1/&ast;1), intermediate metabolizer (IM) (&ast;1/&ast;2 and &ast;1/&ast;3), and poor metabolizer (PM) (&ast;2/&ast;2, &ast;2/&ast;3, and &ast;3/&ast;3) phenotypes, respectively. CYP2C19 &ast;2/&ast;2 genotype frequency was higher, &ast;1/&ast;1 genotype was lower in PCAD patients than controls. Individuals with CYP2C19 PM phenotype had higher triglyceride (TG) levels than those with CYP2C19 EM or IM phenotypes. Logistic regression analysis showed that body mass index (BMI) ≥ 24.0 kg/m2 (≥ 24.0 kg/m2 vs 18.5– 23.9 kg/m2, odds ratio (OR): 1.326, 95% confidence interval (CI): 1.041– 1.688, p = 0.022), smoking (OR: 1.974, 95% CI: 1.283– 3.306, p = 0.002), hypertension (OR: 1.327, 95% CI: 1.044– 1.687, p = 0.021), diabetes mellitus (OR: 1.390, 95% CI: 1.054– 1.834, p = 0.020), CYP2C19 PM phenotype (PM phenotype vs EM phenotype, OR: 1.701, 95% CI: 1.200– 2.411, p = 0.003), and CYP2C19 IM+PM phenotypes (IM+PM vs EM phenotype, OR: 1.369, 95% CI: 1.077– 1.740, p = 0.010) were associated with PCAD.Conclusion: CYP2C19 PM or IM+PM phenotypes, overweight, smoking, hypertension, and diabetes mellitus were associated with PCAD.Keywords: premature coronary artery disease, cytochrome P450, CYP2C19, loss-of-function

Zijun Wu,1,&ast; Ruijing Wang,1,&ast; Yuanjun Liu,1 Bin Yang,2 Huiping Wang1 1Department of Dermatovenereology, Tianjin Medical University General Hospital/Tianjin Institute of Sexually Transmitted Disease, Tianjin, People’s Republic of China; 2Department of Burn and Plastic Surgery, General Hospital of Central Theater Command, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Yang, Department of Burn and Plastic Surgery, General Hospital of Central Theater Command, Wuhan, Hubei, People’s Republic of China, Email sszxkyb1@163.com Huiping Wang, Department of Dermatovenereology, Tianjin Medical University General Hospital/Tianjin Institute of Sexually Transmitted Disease, Tianjin, People’s Republic of China, Email huiping1208@163.comBackground: Psoriasis is characterized by accelerated proliferation of epidermal keratinocytes. IL-27 is relevant to psoriasis pathogenesis. We previously found that IL-27 stimulates the proliferation of keratinocytes. However, the mRNAs involved in the process have not been fully studied. This study aims to identify potential pathways and hub genes associated with proliferation in keratinocytes with IL-27 intervention by bioinformatics analysis.Methods: The mRNA expression profiles from HaCaT cells with or without IL-27 treated were analyzed by bioinformatics tools. The protein–protein interaction (PPI) network was constructed to screen gene clusters and hub genes associated with proliferation. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to identify the function of the mRNAs. The GEO database and quantitative real-time PCR (qPCR) were used to verify the expression levels of hub genes in psoriatic skin lesions and IL-27-treated psoriasiform keratinocytes, respectively.Results: We found 1257 differentially expressed genes and screened 2 crucial gene clusters. GO analysis revealed that Cluster 1 was mainly enriched in “Mitotic sister chromatid segregation” and “Spindle”. Cluster 2 was mainly enriched in the “Pyruvate metabolic process” and “Oxidoreductase complex”. KEGG analysis showed that Cluster 1 and Cluster 2 were mainly enriched in “Cell cycle” and “Glycolysis/Gluconeogenesis”, respectively. We then identified 6 hub genes enriched in the two pathways, including CCNB1, PTTG1, CDC20, PLK1, PKM, and LDHA. GSEA complemented the role of the mitochondrial “Oxidative phosphorylation” pathway. Moreover, we found that 6 hub genes were upregulated in psoriasis skin lesions and IL-27 elevated the hub genes expression in M5-induced psoriasiform keratinocytes.Conclusion: IL-27 possibly promotes glycolysis, mitochondrial oxidative phosphorylation, and cell cycle progression in keratinocytes. Additionally, we identified CCNB1, PTTG1, CDC20, PLK1, PKM, and LDHA as hub genes that may be involved in the mechanism of IL-27 facilitating keratinocyte proliferation in psoriasis.Keywords: psoriasis, glycolysis, oxidative phosphorylation, bioinformatics

Minghui Li,1,&ast; Jiabi Wu,1,&ast; Tao Yang,1 Yuhang Zhao,1 Ping Ren,1 Lingling Chang,2 Pilong Shi,1 Jing Yang,1 Yuhang Liu,2 Xiaolei Li,3 Peng Wang,2 Yonggang Cao1 1Department of Pharmaceutics, Harbin Medical University, Heilongjiang, 163319, People’s Republic of China; 2Department of Physiology, Harbin Medical University, Heilongjiang, 163319, People’s Republic of China; 3Department of Pathology, Jiangsu College of Nursing, Jiangsu, 223003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Wang, Department of Physiology, Harbin Medical University, Xinyang Road 39, Gaoxin District, Daqing, Heilongjiang, People’s Republic of China, Email wangpeng810122@126.com Yonggang Cao, Department of Pharmaceutics, Harbin Medical University, Xinyang Road 39, Gaoxin District, Daqing, Heilongjiang, People’s Republic of China, Email caoyonggang@hmudq.edu.cnBackground: Cardiac microvascular damage is substantially related with the onset of myocardial ischaemia-reperfusion (IR) injury. Reportedly, allicin (AL) effectively protects the cardiac microvascular system from IR injury. However, the unsatisfactory therapeutic efficacy of current drugs and insufficient drug delivery to the damaged heart are major concerns. Here, inspired by the natural interaction between neutrophils and inflamed cardiac microvascular endothelial cells (CMECs), a neutrophil membrane-camouflaged nanoparticle for non-invasive active-targeting therapy for IR injury by improving drug delivery to the injured heart is constructed.Methods: In this study, we engineered mesoporous silica nanoparticles (MSNs) coated with a neutrophil membrane to act as a drug delivery system, encapsulating AL. The potential of the nanoparticles (named AL@MSNs@NM) for specific targeting of infarcted myocardium was assessed using small animal vivo imaging system. The cardiac function of AL@MSNs@NM after treatment was evaluated by Animal Ultrasound Imaging system, HE staining, and Laser Speckle Imaging System. The therapeutic mechanism was analyzed by ELISA kits, immunofluorescence, and PCR.Results: We discovered that AL@MSNs@NM significantly improves cardiac function index, reduced infarct size and fibrosis, increased vascular perfusion in ischemic areas, and also promoted the function of CMECs, including migration, tube formation, shear stress adaptation, and nitric oxide production. Further research revealed that AL@MSNs@NM have cardio-protective functions in IR rats by inhibiting CMEC ferroptosis and increasing platelet endothelial cell adhesion molecule-1 (PECAM-1) expression.Conclusion: Our results indicated that AL@MSNs@NM significantly reversed CMEC ferroptosis and increased PECAM-1 expression, enhanced cardiac function, and reduced myocardial infarction size. Therefore, this strategy demonstrates that engineered biomimetic nanotechnology effectively delivers AL for targeted therapy of myocardial infarction.Keywords: neutrophil membrane, ischemia-reperfusion, allicin, cardiac microvascular endothelial cells, ferroptosis

Zhiyang Wu,1,&ast; Wenjun Lu,2,&ast; Xin Zhang,1 Qiaoying Xia,2 Han Zuo,2 Xi Guo,1 Yu Liu,1 Fan Zhang,3 Xin Zhang,4 Luyao Zhang2 1Department of Critical Care Medicine, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 2Department of Pathology and Pathophysiology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Department of Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 4Department of General Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Luyao Zhang, Department of Pathology and Pathophysiology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China, Email zhangluyao@njucm.edu.cn Xin Zhang, Department of General Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China, Email 514557061@qq.comPurpose: Protectin D1 (PD1), a biologically active molecule derived from docosahexaenoic acid (DHA), plays a major role in the body’s endogenous lipid-mediated inflammatory response. The study aims to explore the relationship between PD1, inflammatory response and the severity of acute pancreatitis (AP).Patients and Methods: Sixty consecutive AP patients within 72h of disease onset were enrolled as the study group, a further thirty healthy people were enrolled as the control group. General demographics collected at the time of enrollment. Serum PD1, Citrullinated Histone 3 (CitH3), myeloperoxidase-Deoxyribonucleic acid (MPO-DNA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) level were measured in AP patients on enrollment day 0, day 1, day 3 and day 7. Meanwhile, the Acute Physiology and Chronic Health evaluation II (APACHE II) scores, Sequential Organ Failure Assessment (SOFA) scores were also evaluated on day 0, day 1, day 3 and day 7.Results: AP was severe in 29 patients (48.3%), moderately severe acute pancreatitis (MSAP) was found in 9 patients (15%), and mild acute pancreatitis (MAP) was found in 22 patients (36.7%). The level of PD1, CitH3 and MPO-DNA were statistically significantly higher in AP patients than in the healthy population. Serum PD1, CitH3 and MPO-DNA concentration increased with AP severity. In AP patients, PD1 has a strong linear association with TNF-α, CitH3 and MPO-DNA. The AUC for SAP predicted by PD1 was 0.938. The calculated cut-off point for prognosis SAP is 7.94 pg/mL. The AUC for infected pancreatic necrosis (IPN) predicted by PD1 was 0.836 and the cut-off point was 8.65 pg/mL. The AUC for organ failure (OF) predicted by PD1 was 0.719 and the cut-off point was 7.94 pg/mL.Conclusion: PD1 is associated with both the presence of AP and the severity of pancreatitis.Keywords: PD1, acute pancreatitis, CitH3, MPO-DNA, infected pancreatic necrosis, organ failure

Xiaoping Xu, Han Wu, Yang Liu Department of Obstetrics and Gynecology, Deyang People’s Hospital, Deyang, Sichuan, People’s Republic of ChinaCorrespondence: Yang Liu, Department of Obstetrics and Gynecology, Deyang People’s Hospital, 173 North Taishan Road Taishan North Road, Deyang, Sichuan, 61800, People’s Republic of China, Email 18783861321@163.comPurpose: To evaluate the association between Composite Dietary Antioxidant Index (CDAI) and the risk of endometriosis in American women.Methods: The study adopted a cross-sectional design, incorporating 3862 women aged over 20 years, selected from the National Health and Nutrition Examination Survey (NHANES) dataset from 2001 to 2006. Six dietary antioxidants were taken into account in calculating CDAI. Endometriosis was determined based on self-report. To evaluate the association between CDAI and the risk of endometriosis, we employed models with multivariable logistic variables. For subgroup assessment in relation to CDAI, a stratified multivariate logistic regression model was utilized.Results: Among all participants, 273 participants (7.1%) were found to exhibit endometriosis. The preliminary analysis showed a reverse association between CDAI and the likelihood of endometriosis (odds ratio [OR] = 0.95; 95% confidence interval [CI]: 0.92~0.98). Upon full adjustment within the multivariable logistic regression, the ORs (95% CI) for endometriosis prevalence per unit increase in CDAI were estimated to be 0.96 (0.93~1). When the CDAI levels were divided into quartiles, it was found that the ORs for endometriosis with CDAI levels in Q2 (− 2.131– 0.023), Q3 (0.023– 2.650), and Q4 (2.650– 42.854) were 0.74 (0.52, 1.05), 0.76 (0.53, 1.1), and 0.53 (0.36, 0.79), respectively, compared to those with CDAI levels in Q1 (− 7.151–− 2.131). We evaluated the association between CDAI and endometriosis using subgroups stratified by age, race/ethnicity, education level, body mass index (BMI), oral contraceptive, and menopausal status, revealing a substantial negative relationship.Conclusion: In this cross-sectional study, increasing CDAI was proportionally associated with a reduced risk of endometriosis among American women, suggesting a diet high in antioxidants may play an important role in reducing the risk of endometriosis. The findings of NHANES data spanning 2001 to 2006 suggest that promoting antioxidant-rich diets could be an important prevention strategy for endometriosis.Keywords: composite dietary antioxidant index, endometriosis, National Health and Nutrition Examination Survey, cross-sectional study

Linqiong Liu,1– 3,&ast; Pengfei Huang,1,2,&ast; Changsong Wang,1,2,&ast; Yuxi Liu,1– 3 Yan Gao,3 Kaijiang Yu1,2 1Departments of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Heilongjiang Provincial Key Laboratory of Critical Care Medicine, Harbin Medical University, Harbin, People’s Republic of China; 3Departments of Critical Care Medicine, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Gao, Departments of Critical Care Medicine, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China, Email icugaoyan@163.com Kaijiang Yu, Departments of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China, Email drkaijiang@163.comPurpose: We aimed to identify the association between heart failure (HF) with sepsis and its mortality through Mendelian randomization (MR) and observational studies.Patients and Methods: In MR study, we utilized public summary statistics from genome-wide association studies (GWAS). We conducted univariable, multivariable and network MR analyses to investigate causal relationships between HF and sepsis, and mediating roles of cytokines and growth factors. We performed an observational analysis using the MIMIC-IV database. Propensity score matching (PSM) and logistic regression models were employed to explore causal relationships between HF and sepsis, besides short-, medium-, and long-term mortality associated with sepsis.Results: In univariable MR analysis, there was a causal relationship between genetically predicted HF (OR = 1.15, 95% CI = 1.02– 1.29, P = 0.025) and sepsis. In multivariable and network MR analyses, βNGF was independently associated with sepsis. And it mediated 17.6% (95% CI 2.45– 30.72%) of HF effect on sepsis. In the real-world observational study, acute on chronic diastolic (congestive) heart failure (DCHF) (OR = 1.59, 95% CI = 1.31– 1.93, P < 0.001), acute DCHF (OR = 2.52, 95% CI = 1.61– 3.95, P = 0.010), and acute diastolic heart failure (DHF) (OR = 1.52, 95% CI = 1.06– 2.19, P = 0.024) after PSM were associated with occurrence of sepsis. Chronic systolic (congestive) heart failure (SCHF) was associated with increased 28-day (OR = 1.75, 95% CI = 1.06– 2.91, P = 0.030), 1-year (OR = 1.80, 95% CI = 1.08– 3.00, P = 0.023), and 2-year (OR = 1.86, 95% CI = 1.12– 3.10, P = 0.018) mortality in sepsis.Conclusion: Observational and MR analyses showed a causal relationship between HF and sepsis. Chronic SCHF was related to increased short/long-term mortality in sepsis. Our study indicated βNGF a key factor in HF-induced sepsis.Keywords: βNGF, MIMIC-IV, PSM, GWAS

Nan Chen, Jiadi Gao, Hanshu Zhao, Sihan Liu, Yubing Zhou, Yushuang Liu, Zhongling Zhang, Shanshan Yang Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of ChinaCorrespondence: Shanshan Yang; Zhongling Zhang, Department of Neurology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Stree, Nangang District, Harbin, Heilongjiang Province, 150001, People’s Republic of China, Tel +86-451-85553681 ; + 86-451-85555918, Fax +86-451-85555918, Email yangshanshan81@163.com; zhangzhongling7@126.comObjective: Stroke is a leading cause of disability and mortality worldwide, posing a significant public health challenge. While treatment of acute ischemic stroke (AIS) with recombinant tissue plasminogen activator (rt-PA) is effective but increases the risk of hemorrhagic transformation (HT). This study aimed to explore the determinants of HT in AIS patients treated with rt-PA and investigate the association between blood glucose levels and HT risk.Methods: We conducted a prospective cohort study at the First Affiliated Hospital of Harbin Medical University from January 2018 to December 2021. Patients with AIS and who received rt-PA within 4.5 hours of symptom onset were included. Demographic, clinical, laboratory, and imaging data were collected.Results: Of the 426 patients, 15% experienced HT post-rt-PA, occurred more frequently in patients with a history of cardiac embolism, higher prethrombolysis NIHSS scores, and elevated fasting blood glucose (FBG) levels. The frequency of HT was higher in non-diabetic patients with FBG levels ≥ 7.0 mmol/L compared to diabetic patients. Elevated blood glucose levels were significantly associated with HT, regardless of diabetes history.Conclusion: The findings suggest importance of precise glycemic control during AIS management to improve patient outcomes, particularly in non-diabetic patients. Future protocols for AIS treatment should incorporate these findings to reduce HT risks. Further large-scale studies are needed to confirm these associations and guide clinical practices.Keywords: Acute ischemic stroke, thrombolytic therapy, rt-PA, hemorrhagic transformation, blood glucose, outcomes

Ruixue Zhang,1 Hui Xu,1 Xiaoxue Zhang,1 Hui Xiong,2 Fei Tang,3 Liping Lv,3 Xiangdong Mu,4 Wei Tian,5 Yueguang Cheng,6 JianRong Lu,6 Xiuhong Nie,7 Yang Guo,8 Yingying Liu,9 Zhi Zhang,10 Lianjun Lin1 1Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Emergency, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Interventional Pulmonology, Anhui Province Chest Hospital, Hefei, People’s Republic of China; 4Department of Respiratory, Tsinghua Changgung Hospital, Beijing, People’s Republic of China; 5Department of Geriatrics, Jishuitan Hospital, Beijing, People’s Republic of China; 6Department of Emergency, Jingmei Group General Hospital, Beijing, People’s Republic of China; 7Department of Respiratory, Xuanwu Hospital, Beijing, People’s Republic of China; 8Department of Endoscopic Diagnosis &treatment, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 9CapitalBio Technology Co., Ltd, Beijing, People’s Republic of China; 10Bio Biological Group Co., Ltd, Beijing, People’s Republic of ChinaCorrespondence: Lianjun Lin, Department of Geriatrics, Peking University First Hospital, No. 8 Xishiku Avenue, Beijing, 100034, People’s Republic of China, Email 06474@pkufh.comPurpose: The detection of pathogenic microorganisms plays a significant role in the diagnosis and management of pneumonia that are responsible for a substantial number of deaths worldwide. However, conventional microbiological tests (CMT) have low accuracy and are time-consuming. In this study, we aim to evaluate the clinical value of Chips for Complicated Infection Detection (CCID) in detecting pneumonia pathogens.Patients and Methods: This study was conducted at nine hospitals in China from January 2021 to September 2022. Respiratory samples from adult pneumonia patients were collected from each patient. CMT and CCID were performed in parallel to identify the pathogens.Results: A total of 245 patients were included, with 73% being elderly. CCID identified pathogenic microbes in 78.0% of patients and conventional microbiological tests (CMT) in 57.1% of the patients (p< 0.001). The overall positive and negative percent agreements between CCID and CMT for pathogen detection were 90.07% and 38.46%, respectively. 38.8% of patients were diagnosed with mixed infections with at least two pathogens by CCID. Bacterial infections identified by CCID accounted for 60.0% of 245 patients, with the top 3 being Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterococcus faecium, respectively. K. pneumoniae was the most common pathogen in elderly patients, with a significantly higher prevalence compared to non-elderly patients (p = 0.0011). Among the 197 patients who had used antibiotics before sample collection, the positive rate of CCID was significantly higher than that of CMT (p < 0.001).Conclusion: This study indicates that compared to CMT, this novel chip has significant advantages in detecting pathogens in pneumonia patients, especially in the elderly.Keywords: pneumonia, elderly, pathogens, chip, LAMP

Weichao Li,1,2 YuYan Liu,2 Xunhu Gu1 1Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Anesthesiology, Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University, QingYuan, Guangdong, People’s Republic of ChinaCorrespondence: Xunhu Gu, Doctor of Medicine (MD), Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China, Email 540523118@qq.comBackground: Catecholamine vasopressors are commonly used for intra- or post-operative hypotension for cardiac surgery, which have a side effect of new-onset atrial fibrillation (AF) and myocardial ischemia. However, it is not entirely clear whether catecholamine vasopressors increase the risk of new-onset AF after noncardiac surgery.Aim: The aim of this study was to analyze the association between the use of catecholamine vasopressors and the risk of developing new-onset AF after noncardiac surgery.Methods: In this prospective trial, available data from eligible elderly individuals receiving noncardiac surgery at a single center from November 2022 to January 2024 were gathered. Propensity score matching (PSM) was used to balance patient baseline characteristics and to control for confounders. To determine the association between catecholamine vasopressors and the risk of new-onset AF, univariate and multivariate logistic regression analyses were performed.Results: A total of 6000 subjects were included in this study (mean [SD] age, 70.73 [6.37] years; 910 [50.9%] males). After PSM, the patients were stratified into catecholamine vasopressor (n = 357) and comparator groups (n = 1432). A total of 18/357 patients in the catecholamine vasopressor group developed AF, and 25/1432 patients in the comparator group developed AF (incidence rate, 5.0% vs 1.7%). Compared with the comparator group, the catecholamine vasopressor group had an increased risk of new-onset AF (aOR, 2.77; 95% CI, 1.28– 5.89). Some sensitivity analyses also revealed consistent findings of increased new-onset AF risk associated with catecholamine vasopressor treatment.Conclusion: The findings from this study suggest that catecholamine vasopressor treatment is associated with an increased risk of new-onset AF and may help physicians select a modest medication for patients while also assessing the risk of new-onset AF. Keywords: catecholamine vasopressors, new-onset atrial fibrillation, risk, prospective trial, noncardiac procedures

Caina Liu,1,&ast; Qingqing Zhang,1,2,&ast; Yiming Liu,1 Zixu Wang,1 Fangchen Chen,1 Yitian Li,1 Yami Zhao,1 Jing Zhu,1 Dandan Li,1,3– 5 Chunyan Zhu1– 4,6 1School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, 230032, People’s Republic of China; 2Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, 230000, People’s Republic of China; 3Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, 230032, People’s Republic of China; 4Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health, Hefei, 230032, People’s Republic of China; 5Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 6Department of Psychology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dandan Li; Chunyan Zhu, Email 799200213@qq.com; ayswallow@126.comPurpose: Higher rates of depression are associated with autistic traits; however, the precise association between autistic traits and depression has yet to be fully elucidated. Good interpersonal emotional regulation and social self-efficacy are crucial for mental health; therefore, in this study, we investigated the relationships between autistic traits, interpersonal emotional regulation, social self-efficacy, and depression.Patients and Methods: In total, 1024 participants (613 females and 411 males) aged 16 to 23 years old (M = 19.03, SD = 0.95) completed questionnaires that were designed to evaluate their autistic traits, interpersonal emotion regulation, social self-efficacy and depression. Data were analyzed by Spearman correlation and mediation effects analyses.Results: Autistic traits were significantly and positively correlated with depression (r = 0.39, p < 0.001), and autistic traits were shown to positively predict depression (B = 0.28, p < 0.001). Interpersonal emotion regulation and social self-efficacy were found to play a serial mediating role between autistic traits and depression (indirect effect = 0.020, p = 0.006).Conclusion: This study is a supplement to the mechanism of the relationship between autistic traits and depression. Interpersonal emotion regulation and social self-efficacy are important predictors of possible depression in individuals with high autistic traits. These findings suggest combining interpersonal emotional regulation training and exploring the clinical value of interpersonal emotional regulation interventions in individuals with high autistic traits and autism spectrum disorder, aiming to build social confidence, reduce negative moods, restore social functioning, and other aspects.Keywords: autistic traits, depression, interpersonal emotion regulation, social self-efficacy, chain mediation

Guangtong Cao,1 Mingmin Ye,2 Haiyan Wang,3 Yi Liu,1,&ast; Mengzhi Li4,&ast; 1Department of Burns and Plastic Surgery & Wound Repair Surgery, Second Hospital of Lanzhou University, Lanzhou, Gansu, 730030 People’s Republic of China; 2Department of Plastic Surgery, Gansu Provincial Hospital, Lanzhou, Gansu, People’s Republic of China; 3Department of Ultrasound Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 4Department of Hand, Foot, and Microsurgical Reconstruction, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Liu; Mengzhi Li, Email liuyi196402@163.com; sweetlife00@163.comAbstract: Pathological scars, including hypertrophic scar and keloid are the result of excessive tissue repair and are influenced by biomechanical forces like tension, mechanical pressure, and stiffness. These forces significantly impact scar development and progression, affecting wound healing, collagen deposition, and tissue remodeling. Understanding how these mechanical stimuli contribute to scar development is essential for devising effective therapeutic interventions. Clinically, reducing wound tension and applying mechanical pressure are key strategies for managing pathological scars. Techniques like super-tension-reduction suturing, stress-shielding polymers, and force-modulating tissue bridges (FMTB) have been shown to effectively alleviate tension and reduce scar proliferation. Additionally, Pressure Garment Therapy (PGT) is widely used to treat hypertrophic scars by reducing tissue stiffness, limiting collagen buildup, and promoting collagen realignment. Despite challenges such as discomfort and uneven pressure application, ongoing research focuses on enhancing these therapies through mechanosensitive technologies to improve both efficacy and patient comfort. This review highlights the role of biomechanical forces in scar formation and discusses therapeutic approaches that target these forces to improve clinical outcomes.Keywords: pathological scars, biomechanical forces, hypertrophic scar, keloid, tissue remodeling

Lixin Xie,1,&ast; Lihua Feng,1,&ast; Xiaomin Tang,1 Yunping Xu,1 Hengyi Xu,2 Yang Liu1 1Department of Pediatrics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 2State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hengyi Xu, State Key Laboratory of Food Science and Resources, Nanchang University, 235 Nanjing East Road, Nanchang, 330047, People’s Republic of China, Tel +0086-791-8830-4447-ext-9520, Fax +0086-791-8830-4400, Email kidyxu@163.com; HengyiXu@ncu.edu.cn Yang Liu, Department of Pediatrics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1 minde Road, Nanchang, 330006, People’s Republic of China, Tel +86-791-8631-1209, Email ocean3166@yeah.netPurpose: To evaluate the therapeutic effect of oral administration of Lactiplantibacillus plantarum P101 (P101) on skeletal injury in young rats exposed to titanium dioxide nanoparticles (TiO2 NPs), and explore the potential mechanism.Methods: Four-week-old male rats were orally administration to TiO2 NPs and supplemented with P101 2 hours later for 4 weeks. The growth and development, food intake, bone metabolism and serum inflammatory markers of the rats were evaluated. Their tibias were observed and evaluated using microcomputed tomography (micro-CT), tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry (IHC) and real-time quantitative PCR (RT-qPCR). We observed the tibia growth plate using safranin and fast green staining. 16S rDNA sequence analysis of fecal samples was performed to observe changes in the gut microbiota.Results: Our results showed that TiO2 NPs can lead to bone growth inhibition and osteoporosis, induce intestinal flora imbalance, and induce inflammation in young rats. Further mechanistic studies suggested that TiO2 NPs disrupts intestinal flora and increases serum IL-1β levels, which increased the expression of RANKL in bone, thereby enhancing osteoclast differentiation and function, leading to bone loss. Through a P101 supplementation experiment, we found that P101 ameliorated the inflammation and osteoporosis on bone caused by TiO2 NPs.Conclusion: This study showed that the mechanism by which P101 alleviates bone damage caused by TiO2 NPs may be through restoring intestinal microbial homeostasis and inhibiting inflammatory response. Keywords: TiO2 NPs, P101, young rats, intestinal flora, bone injury, IL-1&#x03B2

Yuting Wang,&ast; Yan Liu,&ast; Kan Liu, Yuan He, Hui Ding Department of Pulmonary and Critical Care Medicine, Yixing People’s Hospital Affiliated to Jiangsu University, Yixing, Jiangsu Province, 214200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Ding, Email dh1350519@163.comAbstract: Chronic obstructive pulmonary disease (COPD) is one of the most common clinical respiratory illnesses, defined by permanent pathological deterioration that leads to respiratory failure. Regarding COPD treatment, oxygen therapy is very important. Non-invasive positive pressure ventilation (NPPV) is a technique for non-invasive mechanical ventilation that enables patients to get positive pressure support without the need of an artificial airway. Instead, it merely employs the mask by covering the mouth and nose, or simply the nose of patients. NPPV has been shown to be beneficial for COPD patients experiencing respiratory failure. High-flow nasal cannula (HFNC) oxygen therapy shows some advantages, including the reduction of anatomical dead space, the prompt correction of low oxygen levels as well as the improvement of patients’ tolerance. Owing to its continuous progress, ventilation technology strongly improves COPD treatment. In this study, the authors analyze the application of NPPV and HFNC in COPD so as to provide recommendations for mechanical ventilation treatment.Keywords: chronic obstructive pulmonary disease, high flow nasal cannula, non-invasive positive pressure ventilation, respiratory failure

Liyan Wu,1 Zhenyan Yuan,1 Min Wang,1 Xiaomeng Fu,1 Xiaohui Liu,1 Bing Wei,2 Yugeng Liu1 1Department of Infectious Diseases and Clinical Microbiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, People’s Republic of China; 2Emergency Medicine Clinical Research Center, Beijing Chaoyang Hospital, Capital Medical University, & Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Clinical Center for Medicine in Acute Infection, Capital Medical University, Beijing, 100043, People’s Republic of ChinaCorrespondence: Bing Wei; Yugeng Liu, Email dr_weibing@126.com; yugeng_liu@126.comPurpose: Sepsis is a life-threatening condition associated with acute organ dysfunction. Iron is an essential trace element for multicellular organisms and almost all microorganisms, and its role in sepsis has been increasingly recognized. The aim of this study was to investigate the changes in iron metabolism in caecal ligation and puncture solution (CLP) -induced septic mice and the effects of hepcidin pretreatment on serum inflammatory marker levels and liver iron metabolism in CLP-induced septic mice.Methods: C57BL/6 mice were given normal saline, CLP (peritonitis model) or 100 μg of hepcidin via intraperitoneal injection. The experimental animals were divided into 4 groups: the control group, model group (CLP), hepcidin pretreatment Groups CLP+hepcidin-2h and CLP+hepcidin-24 h. Blood samples were collected at 6, 12 and 24 hours after CLP surgery, and the mice were euthanized and livers were obtained.Results: ELISA revealed that hepcidin pretreatment, especially 2 hours in advance (p< 0.01), increased the serum hepcidin, TNF-a and IL-6 in CLP-induced septic mice; the serum iron content of CLP-related septic mice decreased (P< 0.01), while the liver iron content increased (P< 0.01); Hepcidin pretreatment reduced the serum iron (P< 0.05) at 6 h and 12 h and liver iron concentrations (P< 0.01) at 6 h, 12 h and 24 h in CLP-related septic mice. Western blotting revealed that the hepatic iron absorption-related proteins transferrin receptor-2 (TFR2), ZRT/IRT-like protein 14 (ZIP14) and divalent meta lion transporter-1 (DMT1) were elevated (P< 0.01); The iron-exporting protein ferroportin (SLC40A1) was decreased (P< 0.01) throughout CLP and CLP+hepcidin sepsis. Compared with CLP group, the protein expressions in the CLP+ hepcidin-2 h group were more obvious than that in the CLP+ hepcidin-24 h group.Conclusion: Hepcidin has proinflammatory effect. Hepcidin exacerbates iron metabolism imbalances in sepsis by influencing the expression of iron absorption-related proteins and iron export-related proteins.Keywords: hepcidin, sepsis, iron metabolism, SLC40A1, liver

Minghui Li,1,&ast; Yuelin Liu,1,&ast; Xu Han,1,&ast; Tao Li,2 Zhizheng Zhang,1 Ningyi Xue,1 Mengdi Liang,1 Ge Ma,1 Tiansong Xia1 1Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tiansong Xia; Ge Ma, Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel +86-25-83718836, Email xiatsswms@163.com; ntmage@sina.comBackground: Aneuploid circulating endothelial cells (CECs) are an indicator in breast cancer (BC). Significant changes of aneuploid CECs occurred during neoadjuvant chemotherapy (NCT). This study aimed to explore the predictive and prognostic values of aneuploid CECs in locally advanced breast cancer (LABC) patients with different NCT responses.Methods: Breast cancer patients received an EC4-T4 NCT regimen. A novel subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) strategy was applied for the detection of CECs (CD45–/CD31+/DAPI+). Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of aneuploid CEC counts in distinguishing NCT-resistant patients from sensitive ones. All patients were observed for progression-free survival (PFS) and overall survival (OS).Results: The CEC counts at any time point did not show the ability to predict the efficacy of NCT. The difference in the CECs between post-chemotherapy levels and baseline could be sufficient to distinguish chemotherapy-resistant cases from other cases in Hormone+Her-2-/+ (HR+) BC patients. Patients with reduction of CECs after all courses of NCT were associated with higher probability of PFS.Conclusion: Variations in aneuploid CECs during NCT may predict chemotherapy response in patients with HR+ breast cancer. The decrease in the number of aneuploid CECs after all courses of NCT indicates better treatment outcomes in patients with LABC.Keywords: circulating endothelial cells, aneuploidy, neoadjuvant chemotherapy, prognosis, locally advanced breast cancer

Dou Zhang,1,2,&ast; Xuyi Liu,1,2,&ast; Xiong Li,3,&ast; Xinyi Cai,1,2 Zhenying Diao,1,2 Long Qiu,1,2 Xuelin Chen,1,2 Yuyu Liu,1,2 Jianbo Sun,1 Daxiang Cui,1,4 Qiaoyuan Ye,5 Ting Yin1,2 1Research Center of Nano Technology and Application Engineering, The First Dongguan Affiliated Hospital, School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong, 523808, People’s Republic of China; 2Dongguan Biomedical Nano Engineering Technology Research Center, Guangdong Medical University, Dongguan, Guangdong, 523808, People’s Republic of China; 3Department of Pharmacy, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, 519000, People’s Republic of China; 4School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China; 5Department of Dermatology and Venereology, Second Clinical Medical College of Guangdong Medical University, Dongguan, Guangdong, 523808, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiaoyuan Ye, Department of Dermatology and Venereology, Second Clinical Medical College of Guangdong Medical University, Dongguan, Guangdong, 523808, People’s Republic of China, Email 13650248189@163.com Ting Yin, Research Center of Nano Technology and Application Engineering, School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong, 523808, People’s Republic of China, Email wsyt132@163.comPurpose: Melanoma is a highly aggressive and dangerous malignant skin tumor and there is an urgent need to develop effective therapeutic approaches against melanoma. The main objective of this study was to construct a multifunctional nanomedicine (GNR@PEG-Qu) to investigate its therapeutic effect on melanoma from the oxidative stress pathway.Methods: First, the nanomedicine GNR@PEG-Qu was synthesized and characterized, and its photothermal and antioxidant properties were confirmed. In addition, in vivo imaging capabilities were observed. Finally, the tumor inhibitory effects of GNR@PEG-Qu in vivo and in vitro as well as its biosafety were observed.Results: GNR@PEG-Qu shows good photothermal and anti-oxidation properties. Following exposure to 1064 nm laser irradiation in the second near-infrared II (NIR-II) window, GNR@PEG-Qu shows anti-tumor ability through low-temperature photothermal therapy (PTT) adjuvant drug chemotherapy. GNR@PEG-Qu makes full use of the antioxidant capacity of quercetin, reduces ROS levels in melanoma, alleviates oxidative stress state, and achieves “oxidative stress avoidance” at the tumor site. Quercetin can also downregulate the expression of the heat shock protein Hsp70, which will improve the thermal sensitivity of the tumor site and enhance the efficacy of low-temperature PTT.Conclusion: GNR@PEG-Qu nanoagent exhibits synergistic treatment and high tumor inhibition effects, which is a promising strategy developed to achieve oxidative stress avoidance and synergistic therapy of melanoma using quercetin (Qu)-coated gold nanorod (GNR@PEG).Keywords: melanoma, gold nanorods, quercetin, chemo-photothermal therapy, oxidative stress

Jifeng Li, Yifei Zeng, Mengjie Wang, Yongxin Liu, Yubo Guo, Wenjie Zhao, Qiao Huang, Dongxiao Zhang Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Dongxiao Zhang, Department of Galactophore Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23, Art Museum Back Street, Dongcheng District, Beijing, 100010, People’s Republic of China, Tel +8617864190977, Email Tzdx_thinking@126.comPurpose: Granulomatous lobular mastitis (GLM) has seen a rising incidence, though its pathogenesis remains unclear, posing challenges for treatment and contributing to high recurrence rates with conventional therapies. While the role of inflammatory and immune factors in GLM has been recognized, a comprehensive clinical evaluation of these markers is still lacking. This study aims to identify potential diagnostic markers and therapeutic targets by comparing immune markers and cytokine levels in GLM patients and healthy controls.Methods: Conducted at Beijing Hospital of Traditional Chinese Medicine, Capital Medical University from July 2023 to May 2024, this study enrolled 30 GLM patients and 15 healthy female controls in a 2:1 ratio. Serum levels of immune markers and cytokines were analyzed to explore their potential association with GLM.Results: The study population comprised 30 GLM patients with a mean age of 33.40 ± 4.12 years and 15 healthy female controls with a mean age of 32.13 ± 6.19 years. Significantly elevated levels of C-reactive protein (CRP), Immunoglobulin A (IgA), Complement Component 3 (C3), Complement Component 4 (C4), Compliment Component 1q (C1q), Alpha1-antit-rypsin (AAT), α 1-acidglycoprotein (AGP), Anti-histone antibodies (Anti-HIS), Anti-Ro52 antibodies (Anti-Ro52), Anti-double stranded DNA antibodies (Anti-dsDNA), Interleukin-6 (IL-6), Interleukin-10 (IL-10), and Tumor Necrosis Factor-α (TNF-α) were observed in GLM patients compared to controls (all P < 0.05). Subgroup analysis revealed higher levels of CRP, C3, C1q, AAT, and AGP in patients with larger mass areas and those with erythema nodosum (all P < 0.05). No significant differences were found in subgroups based on disease duration or recurrence (both P > 0.05).Conclusion: Serum levels of CRP, IgA, AAT, AGP, Anti-HIS, Anti-Ro52, Anti-dsDNA, C3, C4, C1q, IL-6, IL-10, and TNF-α may serve as diagnostic and prognostic indicators for GLM, with CRP, AAT, AGP, and C1q being particularly indicative of disease severity. These markers offer potential therapeutic targets for GLM.Keywords: granulomatous lobular mastitis, peripheral serology, immune markers, cytokine

Na Yu,1,&ast; Mingqin Su,1,&ast; Juan Wang,2 Yakun Liu,1 Jingya Yang,1 Jingyi Zhang,1 Meimei Wang1 1Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, Hefei, 230032, People’s Republic of China; 2Department of Public Health Inspection and Quarantine, School of Public Health, Anhui Medical University, Hefei, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meimei Wang, Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, No. 81, Mei-Shan Road, Hefei, 230032, People’s Republic of China, Email wangmm@ustc.edu.cnBackground: Tumor development and progression is a long and complex process influenced by a combination of intrinsic (eg, gene mutation) and extrinsic (eg, environmental pollution) factors. As a detoxification organ, the liver plays an important role in human exposure and response to various environmental pollutants including nanomaterials (NMs). Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and remains a serious threat to human health. Whether NMs promote liver cancer progression remains elusive and assessing long-term exposure to subtoxic doses of nanoparticles (NPs) remains a challenge. In this study, we focused on the promotional effects of nano zinc oxide (nZnO) on the malignant progression of human HCC cells HepG2, especially aged nZnO that has undergone physicochemical transformation.Methods: In in vitro experiments, we performed colony forming efficiency, soft agar colony formation, and cell migration/invasion assays on HepG2 cells that had been exposed to a low dose of nZnO (1.5 μg/mL) for 3 or 4 months. In in vivo experiments, we subcutaneously inoculated HepG2 cells that had undergone long-term exposure to nZnO for 4 months into BALB/c athymic nude mice and observed tumor formation. ZnCl2 was administered to determine the role of zinc ions.Results: Chronic low-dose exposure to nZnO significantly intensified the malignant progression of HCC cells, whereas aged nZnO may exacerbate the severity of malignant progression. Furthermore, through transcriptome sequencing analysis and in vitro cellular rescue experiments, we demonstrated that the mechanism of nZnO-induced malignant progression of HCC could be linked to the activation of Claudin-2 (CLDN2), one of the components of cellular tight junctions, and the dysregulation of its downstream signaling pathways.Conclusion: Long-term exposure of fresh and aged nZnO promotes hepatocellular carcinoma malignancy by up-regulating CLDN2. The implications of this work can be profound for cancer patients, as the use of various nanoproducts and unintentional exposure to environmentally transformed NMs may unknowingly hasten the progression of their cancers. Keywords: nano zinc oxide, environmental transformation of NPs, long-term exposure, malignant progression of tumors, CLDN2

Ying Liu,1,&ast; Li Wang,2,&ast; Er-Hao Bao,1,&ast; Jia-Hao Wang,1 Lin Yang,1 Lei Wang,1 Long Xia,1 Ben Wang,1 Ping-Yu Zhu1 1Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 2Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping-Yu Zhu, Email zhupingyu@nsmc.edu.cnPurpose: The prevalence of Obstructive Sleep Apnea (OSA) is high, and there are many complications. Few studies have reported the relationship between OSA and kidney stones. The purpose of this study is to explore whether people at risk of OSA will increase the risk of kidney stones.Methods: This was a cross-sectional study, and information was collected through the National Health and Nutrition Examination Survey conducted from 2015 to 2018. Multiple logistic regression analyses were employed to calculate the odds ratios (ORs) and their 95% confidence intervals (CIs) for the link between obstructive sleep apnea and the presence of kidney stones. Additionally, to assess causality and reduce observational biases, five distinct two-sample Mendelian randomization techniques were applied.Results: Following the adjustment for relevant confounders, findings indicated a statistically significant correlation between obstructive sleep apnea (OSA) and higher prevalence of kidney stones (OR = 1.29; 95% CI: 1.00– 1.66). Additionally, using the inverse-variance weighted approach in Mendelian randomization, results suggested a genetic predisposition to OSA might be causally linked to an elevated risk of developing kidney stones (OR: 1.00221, 95% CI 1.00056– 1.00387).Conclusion: OSA promotes the formation of kidney stones, and the treatment and management of OSA can improve or mitigate the occurrence of kidney stones.Keywords: obstructive sleep apnea, kidney stones, national health and nutrition examination survey, Mendelian randomization

Yanfen Liu, Xueyong Lou Department of Endocrinology at Zhejiang University School of Medicine, Jinhua Hospital, Jinhua, People’s Republic of ChinaCorrespondence: Xueyong Lou, Email jhszxyy0710@163.comBackground: The rapid global spread of a new coronavirus disease known as COVID-19 has led to a significant increase in mortality rates, resulting in an unprecedented worldwide pandemic.Methods: The impact of COVID-19, particularly its long-term effects, has also had a profound effect on the health and well-being of individuals.Metabolic syndrome increases the risk of heart and brain diseases, presenting a significant danger to human well-being.Purpose: The prognosis of long COVID and the progression of metabolic syndrome interact with each other, but there is currently a lack of systematic reports.In this paper, the pathogenesis, related treatment and prognosis of long COVID and metabolic syndrome are systematically reviewed.Keywords: Long COVID, Metabolic syndrome, Cardiovascular disease, pathway, drugs

Mengyao Shi,1,&ast; Xueyu Mao,2,&ast; Xuechun Wu,2 Min Chu,2 Huicong Niu,2 Lulu Sun,1 Xinyue Chang,1 Yu He,1 Yi Liu,1 Daoxia Guo,3 Yonghong Zhang,1 Zhengbao Zhu,1 Jing Zhao2,4 1Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 2Department of neurology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 3School of Nursing, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 4Institute of Healthy Yangtze River Delta, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Zhao, Department of Neurology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China, Email zhao_jing@fudan.edu.cn Zhengbao Zhu, Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, 199 Renai Road, Industrial Park District, Suzhou, Jiangsu Province, 215123, People’s Republic of China, Email zbzhu@suda.edu.cnBackground: Prealbumin is a symbol of protein nutrition and is involved in anti-inflammatory and neuron regeneration, but its association with the prognosis of ischemic stroke remains unclear. We aimed to prospectively explore the associations between serum prealbumin levels and adverse clinical outcomes after ischemic stroke in a large-scale cohort study.Methods: We measured serum prealbumin levels among 6609 ischemic stroke patients admitted at Minhang hospital. The primary outcome was composite of death and major disability (modified Rankin Scale [mRS] score ≥ 3) at 3 months after stroke onset, and secondary outcomes included death and the ordered 7-level categorical score of mRS.Results: During 3 months of follow-up, a total of 2118 patients developed the primary outcome. After multivariable adjustment, high prealbumin levels were associated with a decreased risk of primary outcome (odds ratio, 0.71; 95% CI, 0.59– 0.85; Ptrend< 0.0001) when 2 extreme quartiles were compared. Each unit increase of log-transformed prealbumin was associated with a 42% (95% CI, 28-53%) decreased risk of primary outcome. There was a better shift in the distribution of mRS score at 3 months with higher quartiles of serum prealbumin in ischemic stroke patients (Ptrend< 0.0001). Multivariable-adjusted spline regression model showed a linear relationship between prealbumin and the risk of primary outcome (P for linearity = 0.0036).Conclusion: High serum prealbumin level was independently associated with decreased risks of adverse clinical outcomes among ischemic stroke patients. Our findings suggested that prealbumin may be a valuable prognostic biomarker and indicated the importance of keeping nourished in the daily life.Keywords: prealbumin, ischemic stroke, prognosis, cohort study

Luqian Zhan,1,&ast; Ye Zhang,2,&ast; Yanwei Li,3 Chenhui Lin,3 Heyu Zhang,3 Yuntao Liu,3 Jincai He3 1Department of Neurology, Integrated Traditional Chinese and Western Medicine Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Third Department of Cerebrovascular Disease, Cangzhou Central Hospital, Cangzhou, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jincai He; Yuntao Liu, Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China, Email hjc@wmu.edu.cn; 18267850815@163.comPurpose: Acute ischemic stroke (AIS) patients with COVID-19 have severe neurological symptoms and high mortality. It remains unclear how COVID-19 causes unfavorable outcomes. This study aimed to explore the possible mechanism focusing on inflammation and coagulation.Patients and Methods: 109 AIS patients were recruited and followed up 3 months after stroke. We used binary logistic regression to investigate if COVID-19 infection is an independent prognostic factor. To analyze the link between inflammation, coagulation, and neurological outcomes, we used mediation analysis.Results: Compared to the non-COVID-19 group, the COVID-19 group had significantly higher fibrinogen (FIB) (P < 0.001), APTT ratio (P < 0.001), D-dimer (P < 0.001), CRP (P < 0.001). Patients with unfavorable outcomes had a higher incidence of COVID-19 infection (P = 0.002), along with elevated levels of INR (P = 0.005), D-dimer (P < 0.001), and CRP (P = 0.012). The significant association between 3-month functional outcomes and COVID-19 tends to be insignificant (P = 0.294) after adding the covariates of inflammation and coagulation. The mediation analyses showed the APTT ratio mediated the association between COVID-19 and the 3-month outcome (percent mediation = 56.3%). The integrated pathway analysis implicated that the path of COVID-19 infection→CRP→APTT ratio→ 3-month outcome was significant (percent mediation = 18.7%).Conclusion: AIS with COVID-19 had a poorer prognosis. We delineated a more accurate mechanism by which COVID-19 influences functional outcomes: COVID-19 infection→inflammation→endogenous coagulation pathway→poor stroke outcome. This study provided new insight into the pathway mechanisms of AIS with COVID-19.Keywords: COVID-19, Omicron, stroke, mediation analysis, APTT ratio

Ziyan Zhong,1,&ast; Jian Liu,2,&ast; 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&ast;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

Youwen Gong,1 Yongyi Chen,2 Yang Liu3 1Department of Nursing, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde, People’s Republic of China; 2Department of Nursing, Hunan Cancer Hospital, Changsha, People’s Republic of China; 3School of Nursing, University of South China, Hengyang, People’s Republic of ChinaCorrespondence: Youwen Gong, Department of Nursing, Changde Hospital, Xiangya School of Medicine, Central South University (The first People’s hospital of Changde city), Changde, People’s Republic of China, Email 1755144149@qq.comPurpose: To identify the factors affecting Chinese oncology nurses’ competency in coping with death, and their relationship with death attitudes and educational needs.Methods: A national cross-sectional descriptive study was conducted using an online survey of Chinese oncology nurses. Data were collected using the Coping with Death, Death Attitude Profile–Revised, and Death Education Needs Scales. A Pearson’s correlation analysis was used to examine the relationships among the research variables. A multiple linear regression analysis was used to analyze the factors influencing coping with death.Results: The total score of coping with death was 133.57± 26.78, showing a moderate coping level among Chinese oncology nurses. The Pearson’s correlation analysis showed that death attitude was significantly and positively correlated with coping with death competence, and there was a statistically significant positive relationship between coping with death competence and death education needs. Years of oncology care experience, bereavement experience, death attitude, and death education needs were identified as statistically significant factors influencing competency in coping with death. These factors explained 30.6% of the differences in coping with death.Conclusion: This study found that oncology nurses in China exhibited moderate levels of death coping competence, which needs to be improved to provide higher-quality end-of-life care. Further, death attitude and education needs were important factors affecting participants’ coping with death competence. Tailored death education programs and continuing education on death should be provided for oncology nurses, to encourage them to actively participate in death competence-related training and promote an attitude of natural acceptance of death and positive care for terminally ill patients. In the future, virtual reality technology could complete course implementation designs with immersive, conceptual, and interactive characteristics, to enhance the death-coping education program. Nurses with less experience in oncology care and bereavement should improve their competency in coping with death.Keywords: death competence, death attitudes, death education, oncology nurses