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Huizhen Yue,1– 3 Xiaolong Xu,1– 3 Bing Peng,1– 3 Xuanyu Wang,1 Shengnan Zhang,1 Jinhao Tian,4 Shuo Wang,1 Maifen Song,1 Qingquan Liu1– 3 1Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Chinese Medicine, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases, Beijing, People’s Republic of China; 4Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Qingquan Liu, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23 Gallery Backstreet, Dongcheng District, Beijing, People’s Republic of China, Email liuqingquan_2003@126.comPurpose: CaoHuangGuiXiang (CHGX) formula is a traditional Chinese medicine for the treatment of Candida-related infection. However, its antifungal mechanisms against the emerging fungal pathogen Candida auris remain unclear. This study aimed to evaluate the antifungal activity of the dichloromethane extract of CHGX (CHGX-DME) and clarified its antifungal mechanims against C. auris.Methods: The major components of CHGX-DME were identified by ultra-performance liquid chromatography tandem mass spectrometry. Then, the minimal inhibitory concentration (MIC) assay and the time-kill kinetic assay were performed to investigate the in vitro antifungal activity of CHGX-DME against C. auris, including 8 isolates of 4 discrete clades and 2 special phenotypes (filamentous and aggregative). Furthermore, the effect of CHGX-DME on biofilm development was examined. In addition, the in vivo toxicity and efficacy of CHGX-DME were evaluated in a Galleria mellonella infection model.Results: First, 20 major compounds in CHGX-DME were detected and characterized. The MIC50% and MIC90% of CHGX-DME against C. auris isolates ranged from 50– 200 mg/L and 100– 400 mg/L, respectively. At 400 mg/L, CHGX-DME was able to efficiently kill more than 70% and 90% of C. auris cells after 3 hours and 6 hours of treatment, respectively. This notable antifungal activity exhibited a dosage- and time-dependent manner. Moreover, CHGX-DME not only played a critical role in inhibiting the proliferation of filamentous and aggregative cells, but also showed restricting effect on biofilm development in C. auris. Importantly, it significantly improved the survival rate and reduced the fungal burden in G. mellonella infection models, suggesting a remarkable treatment effect against C. auris infection.Conclusion: CHGX-DME exhibited potent antifungal activity against C. auris and significantly ameliorated this fungal infection in the G. mellonella model, confirming that it would be a promising antifungal drug for the troublesome and emerging fungal pathogen C. auris.Keywords: Candida auris, multidrug resistance, CaoHuangGuiXiang formula, aggregative form, biofilm formation, antifungal efficiency

Wei Guo,1 Jing Tian,1 Yajing Wang,1 Yajing Zhang,1 Jingjing Yan,2 Yutao Du,2 Yanbo Zhang,2,3 Qinghua Han1,4 1Department of Cardiology, the 1st Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, People’s Republic of China; 2Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi Province, People’s Republic of China; 3Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Taiyuan, Shanxi Province, People’s Republic of China; 4Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Taiyuan, Shanxi Province, People’s Republic of ChinaCorrespondence: Qinghua Han, Department of Cardiology, the 1st Hospital of Shanxi Medical University, No. 85 South JieFang Road, Yingze District, Taiyuan, Shanxi, People’s Republic of China, Email syhqh@sohu.com Yanbo Zhang, Department of Health Statistics, School of Public Health, Shanxi Medical University, No. 56 South XinJian Road, Yingze District, Taiyuan, Shanxi, People’s Republic of China, Email sxmuzyb@126.comPurpose: This study aimed to develop an integrative dynamic nomogram, including N-terminal pro-B type natural peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR), for predicting the risk of all-cause mortality in HFmrEF patients.Patients and Methods: 790 HFmrEF patients were prospectively enrolled in the development cohort for the model. The least absolute shrinkage and selection operator (LASSO) regression and Random Survival Forest (RSF) were employed to select predictors for all-cause mortality. Develop a nomogram based on the Cox proportional hazard model for predicting long-term mortality (1-, 3-, and 5-year) in HFmrEF. Internal validation was conducted using Bootstrap, and the final model was validated in an external cohort of 338 consecutive adult patients. Discrimination and predictive performance were evaluated by calculating the time-dependent concordance index (C-index), area under the ROC curve (AUC), and calibration curve, with clinical value assessed via decision curve analysis (DCA). Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were used to assess the contributions of NT-proBNP and eGFR to the nomogram. Finally, develop a dynamic nomogram using the “Dynnom” package.Results: The optimal independent predictors for all-cause mortality (APSELNH: A: angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitor (ACEI/ARB/ARNI), P: percutaneous coronary intervention/coronary artery bypass graft (PCI/CABG), S: stroke, E: eGFR, L: lg of NT-proBNP, N: NYHA, H: healthcare) were incorporated into the dynamic nomogram. The C-index in the development cohort and validation cohort were 0.858 and 0.826, respectively, with AUCs exceeding 0.8, indicating good discrimination and predictive ability. DCA curves and calibration curves demonstrated clinical applicability and good consistency of the nomogram. NT-proBNP and eGFR provided significant net benefits to the nomogram.Conclusion: In this study, the dynamic APSELNH nomogram developed serves as an accessible, functional, and effective clinical decision support calculator, offering accurate prognostic assessment for patients with HFmrEF.Keywords: heart failure with mildly reduced ejection fraction, all-cause mortality, risk prediction model, risk strategy, dynamic nomogram

Jiaxin Zan,1,2 Xiaojing Dong,1,2 Hong Yang,1,2 Jingjing Yan,1,2 Zixuan He,3 Jing Tian,3 Yanbo Zhang1,2,4 1Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Taiyuan, People’s Republic of China; 3Department of Cardiology, The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4School of Health Services and Management, Shanxi University of Chinese Medicine, Taiyuan, People’s Republic of ChinaCorrespondence: Jing Tian; Yanbo Zhang, School of Public health, Shanxi Medical University, 56 Xinjian Road, Taiyuan, Shanxi Province, People’s Republic of China, Tel/Fax +86 15535406059, Email 1105551933@qq.com; sxmuzyb@126.comPurpose: This study sought to develop an unbalanced-ensemble model that could accurately predict death outcomes of patients with comorbid coronary heart disease (CHD) and hypertension and evaluate the factors contributing to death.Patients and Methods: Medical records of 1058 patients with coronary heart disease combined with hypertension and excluding those acute coronary syndrome were collected. Patients were followed-up at the first, third, sixth, and twelfth months after discharge to record death events. Follow-up ended two years after discharge. Patients were divided into survival and nonsurvival groups. According to medical records, gender, smoking, drinking, COPD, cerebral stroke, diabetes, hyperhomocysteinemia, heart failure and renal insufficiency of the two groups were sorted and compared and other influencing factors of the two groups, feature selection was carried out to construct models. Owing to data unbalance, we developed four unbalanced-ensemble prediction models based on Balanced Random Forest (BRF), EasyEnsemble, RUSBoost, SMOTEBoost and the two base classification algorithms based on AdaBoost and Logistic. Each model was optimised using hyperparameters based on GridSearchCV and evaluated using area under the curve (AUC), sensitivity, recall, Brier score, and geometric mean (G-mean). Additionally, to understand the influence of variables on model performance, we constructed a SHapley Additive explanation (SHAP) model based on the optimal model.Results: There were significant differences in age, heart rate, COPD, cerebral stroke, heart failure and renal insufficiency in the nonsurvival group compared with the survival group. Among all models, BRF yielded the highest AUC (0.810; 95% CI, 0.778– 0.839), sensitivity (0.990; 95% CI, 0.981– 1.000), recall (0.990; 95% CI, 0.981– 1.000), and G-mean (0.806; 95% CI, 0.778– 0.827), and the lowest Brier score (0.181; 95% CI, 0.178– 0.185). Therefore, we identified BRF as the optimal model. Furthermore, red blood cell count (RBC), body mass index (BMI), and lactate dehydrogenase were found to be important mortality-associated risk factors.Conclusion: BRF combined with advanced machine learning methods and SHAP is highly effective and accurately predicts mortality in patients with CHD comorbid with hypertension. This model has the potential to assist clinicians in modifying treatment strategies to improve patient outcomes. Keywords: coronary heart disease comorbid with hypertension, ensemble learning, balanced random forest, SHAP, Prognosis

XiaoLan Li,1 Min Li,2 Juan Tian,1 Zi-Wei Shi,1 Ling-Zhi Wang,2 Kui Song1 1Department of Hematology, The First Affiliated Hospital of Jishou University, Jishou, Hunan, People’s Republic of China; 2Department of Pharmacy, The First Affiliated Hospital of Jishou University, Jishou, Hunan, People’s Republic of ChinaCorrespondence: Kui Song, Department of Hematology, The First Affiliated Hospital of Jishou University, 26 Century Avenue, Qianzhou, Jishou, Hunan, 416000, People’s Republic of China, Email js_hematology@163.comAbstract: Multiple myeloma (MM) is a malignancy of plasma cells that can cause anemia due to renal failure and bone marrow failure. Secondary polycythemia (SE) is a clinically rare disease that involves the overproduction of red blood cells. To our knowledge, the association of multiple myeloma and polycythemia has been reported, but the association of SE and multiple myeloma is rare and has been infrequently reported in literature. In contrast to anemia, the presence of polycythemia in multiple myeloma patients is a rare finding. A patient of IgA-λ multiple myeloma with secondary erythrocytosis recently admitted to our department is now reported as follows and relevant literature is reviewed to improve clinicians’ awareness of such rare comorbidities.Keywords: multiple myeloma, secondary erythrocytosis

Pingyu An,1 Qiyue Zhao,2 Siyu Hao,3 Xiaodong Wang,4 Jiangtian Tian,5,6 Zhiqiang Ma3 1Basic Medical College, Harbin Medical University, Harbin, People’s Republic of China; 2School of Nursing, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Dermatology, the Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China; 5Department of Cardiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 6The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, People’s Republic of ChinaCorrespondence: Zhiqiang Ma, Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, No. 246, Xuefu Road, Nangang District, Harbin, 150081, People’s Republic of China, Tel +86 18845139619, Email zhiqiangma@hrbmu.edu.cnAbstract: Psoriasis is an immune-mediated inflammatory skin disease where topical therapy is crucial. While various dosage forms have enhanced the efficacy of current treatments, their limited permeability and lack of targeted delivery to the dermis and epidermis remain challenges. We reviewed the evolution of topical therapies for psoriasis and conducted a bibliometric analysis from 1993 to 2023 using a predictive linear regression model. This included a comprehensive statistical and visual evaluation of each model’s validity, literature profiles, citation patterns, and collaborations, assessing R variance and mean squared error (MSE). Furthermore, we detailed the structural features and penetration pathways of emerging drug delivery systems for topical treatment, such as lipid-based, polymer-based, metallic nanocarriers, and nanocrystals, highlighting their advantages. This systematic overview indicates that future research should focus on developing novel drug delivery systems characterized by enhanced stability, biocompatibility, and drug-carrying capacity.Keywords: psoriasis, bibliometric, drug delivery, topical treatment, nanoparticle, nanocarriers

Wenxia Wu,1,2,* Jingwei Tian,1,* Lisha Xiao,1 Haochen Mai,1 Phei Er Saw,3– 5 Meng Zhang1,2 1Department of General Practice, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Department of General Practice, Shenshan Medical Center, Sun Yat-sen Memorial Hospital, Shanwei, Guangdong, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 4Guangzhou Key Laboratory of Medical Nanomaterials, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 5Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-Sen Memorial Hospital, Foshan, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Phei Er Saw; Meng Zhang, Email zhangm7@mail.sysu.edu.cn; caipeie@mail.sysu.edu.cnBackground: The incidence of cancer is increasing, and cancer survivors are also growing exponentially. Cancer is defined as a new chronic disease. Nevertheless, the management of cancer in the form of chronic diseases in China is still in its infancy, without a standardized care model.Objective: This study aimed to explore the current status of management of cancer care from the patient’s perspective.Methods: This cross-sectional study was a questionnaire survey of patients diagnosed with cancer, including information of the current situation of daily medical consultation, status of comorbidity, and expectations of seeking cancer care in future. Chi-square test and logistic regression analysis were used to explore the factors influencing patients’ choice of cancer management mode.Results: A total of 200 cancer patients were included in the study. The majority (n = 150) of cancer patients chose an oncologist in a tertiary hospital for cancer care. Difficulty in registration (45%), time-consuming (34.5%), repeated examinations (34.5%) and different treatment opinions (12.0%) were the main difficulties they encountered currently during tertiary hospital visits. In community hospital, lack of trust in general practitioners (n = 33) and the necessary drugs or testing items in community hospitals (n = 47) were the main difficulties during their visits. Logistic regression analysis showed that male (OR = 2.737, 95% CI, 1.332– 5.627, p = 0.006) and elderly patients (OR = 3.186, 95% CI, 1.172– 8.661, p = 0.023) were more likely to choose general practitioners (GPs) in community hospitals. Twenty-nine (14.5%) patients hope to have an integrated multidisciplinary management in tertiary and community hospitals with the active participation of GPs for cancer care.Conclusion: Improving drug availability, equipment and quality of cancer care services can help to increase cancer patients’ recognition of community hospital. In addition, the multidisciplinary management integrated tertiary hospitals and communities with the participation of GPs is a worth exploring mode that improves the management of cancer care.Keywords: cancer care, chronic disease management, general practitioners, GPs, multidisciplinary

Yanlei Li,1,&ast; Meng Ge,2,&ast; Jinlong Tian,1,&ast; Jinlei Zhou,1,3 Yao Kang,1 Chen Xia,1 Haiyu Shao,1 Yongguang Wang,4 Yazeng Huang,1 Tingxiao Zhao1 1Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People’s Republic of China; 2Department of Orthopedics, Hospital of Traditional Chinese Medicine of Xiaoshan District, Hangzhou, Zhejiang, People’s Republic of China; 3Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Orthopedics, Linping Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tingxiao Zhao; Yazeng Huang, Center for Plastic & Reconstructive Surgery, Department of Orthopedics, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Shangtang Road 158&num;, Hangzhou, Zhejiang, People’s Republic of China, Email spinezhaotingxiao@163.com; huangyazeng2007@163.comPurpose: Percutaneous endoscopic transforaminal lumbar interbody fusion (PE-TLIF) has become one of the most popular minimally invasive surgeries today. However, the issue of hidden blood loss (HBL) in this surgery has received little attention. This study aims to examine the HBL in PE-TLIF surgery and the effect of tranexamic acid (TXA) on blood loss.Methods: In our research, We conducted a retrospective analysis of 300 patients who underwent PE-TLIF from September 2019 to August 2023. They were divided into 2 groups based on whether they received intravenous TXA injection before surgery. The variables compared included: demographic data, pre-and postoperative hemoglobin (HB), hematocrit (HCT), platelets (PLT), red blood cells (RBC), total blood loss (TBL), visible blood loss (VBL), HBL, operation time, postoperative hospital stay, inflammatory markers, coagulation parameters, and adverse events.Results: Regarding demographic characteristics, besides the operation time, no significant differences were observed between the two groups. Compared with the control group, the TXA group showed a significant reduction trend in TBL, HBL, and VBL (P < 0.05). On the first day after surgery, there were significant differences in prothrombin (PT), activated partial thromboplastin time (APTT), and D-dimer (D-D) levels between the two groups. Similarly, HCT also found similar results on the third day after surgery. No adverse events occurred in either group.Conclusion: Research has found that there is a significant amount of HBL in patients undergoing PE-TLIF. Intravenous injection of TXA can safely and effectively reduce perioperative HBL and VBL. Additionally, compared to the control group, the TXA group shows a significant reduction in operation time.Keywords: percutaneous endoscopic transforaminal lumbar interbody fusion, tranexamic acid, total blood loss, visible blood loss, hidden blood loss

Jue Li,1– 3,&ast; Yingxian Dong,1– 3,&ast; Jiawei Guo,4 Lei Wang,1 Jie Tian,1– 3 Li Wang,4 Guowei Che1– 3 1Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3West China Clinical Medical College, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guowei Che, Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China, Tel/Fax +86-28-86298113, Email cheguoweixw@126.comObjective: To evaluate whether using a cocktail of intercostal nerve blocks (TINB) during thoracoscopic surgery results in better clinical outcomes than patient-controlled analgesia (PCIA).Methods: Patients in two medical groups undergoing video-assisted thoracoscopic surgery (VATS) for pulmonary nodules in West China Hospital of Sichuan University were collected consecutively between March 2022 and December 2022. The groups were divided into two subgroups based on their analgesic program, which were TINB group and PCIA group. The primary outcome was the visual analogue scale (VAS) of the two groups at different stage after surgery and after discharge. Any analgesic related adverse events (ARAEs) were also recorded.Results: A total of 230 patients who underwent VATS were enrolled, in which 113 patients (49.1%) received a cocktail TINB after surgery, and 117 patients (50.9%) received a PCIA. After PSM, 62 patients in each group were selected. The difference of resting VAS (RVAS) and active VAS (AVAS) at different stage during hospitalization was only related to the change of period (p < 0.05, p < 0.05), and the two groups showed no significant differences in RVAS or AVAS during hospitalization (p = 0.271, p = 0.915). However, the rates of dizziness (4.84% vs 25.81%, p = 0.002), nausea and vomiting (0 vs 22.58%, p < 0.05), fatigue (14.52% vs 34.87%, p = 0.012), and insomnia (0 vs 58.06%, p < 0.05) in TINB group were lower than that in PCIA group. Besides, AVAS and RVAS at 7, 14, and 30 days after discharge in TINB group were both significantly lower than that in PCIA group (p < 0.05, p < 0.05).Conclusion: Cocktail TINB provided better analgesia after discharge and reduced the incidence of ARAEs in patients undergoing VATS. Keywords: analgesia, thoracoscopic intercostal nerve block, cocktail analgesia, video-assisted thoracoscopic surgery

There is ongoing interest in free-flowing routines in early childhood education and care settings (ECEC), however little is known about educators' perceptions of free-flowing routines. Therefore, the aim of this study was to explore the perceptions of educators regarding free-flowing routines. A focus group and five semi-structured interviews were conducted. Four main themes were identified: learning outcomes, learning opportunities, team characteristics, and pedagogy and practice. Free-flowing routines may offer additional affordances for children's learning compared to structured routines, such as greater independence and agency for children, sustained time to engage in child-led learning, and deeper engagement in learning. Quality pedagogical practice was perceived as being highly important in free-flowing routines. It is recommended that ECEC settings implement an aspect of free-flowing routines for part, or all of the day, and be open to the learning opportunities that this may present for children. With further research, there is potential to better understand routines that best support children's learning and development in ECEC, as well as opportunities to influence national and international policy and curricula.

Siyu Hao,1,2,&ast; Jiuyi Cong,1,&ast; Zhiqiang Ma,1,2 Yan Xia,3 Yu Zhang,1 Nannan Tong,1 Jiangtian Tian,2,4 Yuzhen Li1 1Department of Dermatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, People’s Republic of China; 3Scientific Research Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuzhen Li; Jiangtian Tian, Email liyuzhen@hrbum.edu.cn; tianjiangtian@126.comBackground: Psoriasis, a chronic inflammatory disorder with an unknown cause, significantly impacts the physical and psychological well-being of patients. However, current biomarkers related to psoriasis lack clinical specificity, sensitivity, and predictive ability.Methods: In this study, we collected skin lesion tissues from 20 psoriasis patients and 20 normal skin samples. Additionally, we obtained four datasets from the GEO database, which included human psoriasis and healthy specimens. We utilized SVM-RFE analysis and the LASSO regression model to identify potential biomarkers. Furthermore, we examined the composition of immune cell types in psoriasis and their correlation with specific genes.Results: Our investigation revealed 57 differentially expressed genes (DEGs), and we identified significantly enriched pathways through KEGG pathway analysis. The results of machine learning and WGCNA suggested that LCE3D and SPRR1B could potentially be used as marker genes for diagnosing psoriasis. RT-PCR and immunohistochemical detection confirmed the abnormally high expression of the SPRR1B gene in psoriasis. Analysis of immune cell infiltration revealed a strong positive correlation between SPRR1B and Macrophages M0 and T cells follicular helper, while showing the strongest negative correlation with resting Mast cells. In addition, we found that silencing SPRR1B in IFN-γ-treated HaCat cells could significantly reduce the increase in IL-17, IL-22, KRT6, and KRT16 caused by IFN-γ.Conclusion: These findings suggest that SPRR1B may have a significant role in the pathogenesis of psoriasis and could be employed as a novel immunomarker for its development.Keywords: psoriasis, SPRR1B, keratinocyte, immunomarkers, immunohistochemistry

Fangzhou Hu,1,&ast; Yunfei Zhu,1,&ast; Jingluan Tian,1 Hua Xu,1,2 Qun Xue1 1Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China; 2Department of Neurology, Affiliated Jintan Hospital of Jiangsu University, Changzhou Jintan First People’s Hospital, Changzhou, Jiangsu, 215006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qun Xue, Email qxue_sz@163.comBackground: Multiple sclerosis (MS) causes chronic inflammation and demyelination of the central nervous system and comprises a class of neurodegenerative diseases in which interactions between multiple immune cell types mediate the involvement of MS development. However, the early diagnosis and treatment of MS remain challenging.Methods: Gene expression profiles of MS patients were obtained from the Gene Expression Omnibus (GEO) database. Single-cell and intercellular communication analyses were performed to identify candidate gene sets. Predictive models were constructed using LASSO regression. Relationships between genes and immune cells were analyzed by single sample gene set enrichment analysis (ssGSEA). The molecular mechanisms of key genes were explored using gene enrichment analysis. An miRNA network was constructed to search for target miRNAs related to key genes, and related transcription factors were searched by transcriptional regulation analysis. We utilized the GeneCard database to detect the correlations between disease-regulated genes and key genes. We verified the mRNA expression of 4 key genes by reverse transcription-quantitative PCR (RT‒qPCR).Results: Monocyte marker genes were selected as candidate gene sets. CD3D, IL2RG, MS4A6A, and NCF2 were found to be the key genes by LASSO regression. We constructed a prediction model with AUC values of 0.7569 and 0.719. The key genes were closely related to immune factors and immune cells. We explored the signaling pathways and molecular mechanisms involving the key genes by gene enrichment analysis. We obtained and visualized the miRNAs associated with the key genes using the miRcode database. We also predicted the transcription factors involved. We used validated key genes in MS patients, several of which were confirmed by RT‒qPCR.Conclusion: The prediction model constructed with the CD3D, IL2RG, MS4A6A, and NCF2 genes has good diagnostic efficacy and provides new ideas for the diagnosis and treatment of MS.Keywords: multiple sclerosis, biomarker, peripheral blood, prediction model

Yushen Jin,1 Zhongquan Cheng,2 Zhu Yuan,2 Yang Du,3 Jie Tian,3 Bing Shao1,4 1Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Centre for Disease Prevention and Control, Beijing, 100013, People’s Republic of China; 2Department of General Surgery, Capital Medical University, Beijing Friendship Hospital, Beijing, 100050, People’s Republic of China; 3CAS Key Laboratory of Molecular Imaging, Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, People’s Republic of China; 4College of Veterinary Medicine, China Agricultural University, Beijing, 100193, People’s Republic of ChinaCorrespondence: Bing Shao; Jie Tian, Email shaobingch@sina.com; jietian@ia.ac.cnPurpose: Liver cancer is considered as the third leading cause of cancer-related deaths, with hepatocellular carcinoma (HCC) accounting for approximately 90% of liver cancers. Improving the treatment of HCC is a serious challenge today. The primary objective of this study was to construct SP94-Fe3O4@ICG&DOX nanoparticles and investigate their potential diagnosis and treatment effect benefits on HCC.Methods: Firstly, we synthesized and characterized SP94-Fe3O4@ICG&DOX nanoparticles and confirmed their in vitro release behavior, photothermal and photodynamic performance. Moreover, the in vivo imaging capability was also observed. Finally, the inhibitory effects on Hepa1-6 in vitro and in vivo were observed as well as biosafety.Results: SP94-Fe3O4@ICG&DOX nanoparticles have a size of ~22.1 nm, with an encapsulation efficiency of 45.2% for ICG and 42.7% for DOX, showing excellent in vivo MPI and fluorescence imaging capabilities for precise tumor localization, and synergistic photo-chemotherapy (pH- and thermal-sensitive drug release) against tumors under irradiation. With the assistance of a fluorescence molecular imaging system or MPI scanner, the location and contours of the tumor were clearly visible. Under a constant laser irradiation (808 nm, 0.6 W/cm2) and a set concentration (50 μg/mL), the temperature of the solution could rapidly increase to ~45 °C, which could effectively kill the tumor cells. It could be effectively uptaken by HCC cells and significantly inhibit their proliferation under the laser irradiation (100% inhibition rate for HCC tumors). And most importantly, our nanoparticles exhibited favorable biocompatibility with normal tissues and cells.Conclusion: This versatile agent can serve as an intelligent and promising nanoplatform that integrates multiple accurate diagnoses, precise positioning of cancer tissue, and effective coordination with synergistic tumor photodynamic therapy. Keywords: porous hollow structure, magnetic particle imaging, fluorescence imaging, synergistic treatment, theranostics

Ying Zhao, Jing Tian, Cuie Gao, Lu Liu, Linxin Pan, Zhiqiang Song Department of Dermatology, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Zhiqiang Song, Department of Dermatology, Southwest Hospital, Army Medical University, No. 30, Gaotanyan Street, Shapingba District, Chongqing, 400038, People’s Republic of China, Email drsongzq@hotmail.comBackground: Blood eosinophilia is often associated with various dermatoses, such as atopic eczema, urticaria, drug eruption, bullous pemphigoid, and hypereosinophilic syndrome (HES). Differential diagnosis is very challenging due to the similarities of clinical and pathological characteristics.Purpose: To investigate and analyze the clinical characteristics of dermatoses associated with blood eosinophilia (DABE) to further optimize disease management.Patients and Methods: We conducted a retrospective analysis on 397 DABE patients with blood absolute eosinophil count (AEC) greater than or equal to 0.5× 109/L. Clinical characteristics, laboratory values, treatment course, and associated diagnoses were evaluated. All DABE patients were grouped based on the severity of eosinophilia as mild group (0.5 ≤ AEC× 109/L < 1.5), moderate group (1.5 ≤ AEC× 109/L < 3), and severe group (AEC× 109/L ≥ 3).Results: Our study revealed three distinct patterns: (1) Mild eosinophilia associated with localized skin lesions, atopic history, mildly elevated total serum IgE level, diagnosed with eczema/dermatitis, and frequent antihistamines use. (2) Moderate eosinophilia has the characteristics of both mild group and severe group. (3) The severe eosinophilia group had a high proportion of elderly people without atopic history, but with acute onset, generalized skin lesions, and high level of lactate dehydrogenase, and the majority of them were diagnosed with systemic diseases (HES or tumor).Conclusion: We summarize the clinical rules of dermatoses associated with blood eosinophilia, hoping to facilitate the diagnosis and treatment for patients.Keywords: eosinophilia, diagnosis, eczema, psoriasis, drug eruption

Jiaqi Tian,1,&ast; Zhengpu Han,1,2,&ast; Dandan Song,1 Yanjie Peng,1 Min Xiong,3 Zhen Chen,2 Shuyin Duan,4 Lin Zhang1,5 1Clinical Medical Research Center for Women and Children Diseases, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, People’s Republic of China; 2School of Public Health, Weifang Medical University, Weifang, People’s Republic of China; 3School of Public Health, North China University of Science and Technology, Tangshan, People’s Republic of China; 4School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 5Key Laboratory of Birth Defect Prevention and Genetic Medicine of Shandong Health Commission, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Zhang, Clinical Medical Research Center for Women and Children Diseases, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250001, People’s Republic of China, Tel +86-531-68795046, Email zhanglin8901@163.com Shuyin Duan, School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250001, People’s Republic of China, Tel +86-13419581411, Email shuyinduan@126.comAbstract: Exosomes are nano-sized membrane vesicles that transfer bioactive molecules between cells and modulate various biological processes under physiological and pathological conditions. By applying bioengineering technologies, exosomes can be modified to express specific markers or carry therapeutic cargo and emerge as novel platforms for the treatment of cancer, neurological, cardiovascular, immune, and infectious diseases. However, there are many challenges and uncertainties in the clinical translation of exosomes. This review aims to provide an overview of the recent advances and challenges in the translation of engineered exosomes, with a special focus on the methods and strategies for loading drugs into exosomes, the pros and cons of different loading methods, and the optimization of exosome production based on the drugs to be encapsulated. Moreover, we also summarize the current clinical applications and prospects of engineered exosomes, as well as the potential risks and limitations that need to be addressed in exosome engineering, including the standardization of exosome preparation and engineering protocols, the quality and quantity of exosomes, the control of drug release, and the immunogenicity and cytotoxicity of exosomes. Overall, engineered exosomes represent an exciting frontier in nanomedicine, but they still face challenges in large-scale production, the maintenance of storage stability, and clinical translation. With continuous advances in this field, exosome-based drug formulation could offer great promise for the targeted treatment of human diseases.Keywords: engineered exosomes, drug delivery, clinical application, preparation strategy

Dan Han,1,2 Jing Tian,3 Junfeng Zhao,2 Shaoyu Hao4,5 1Department of Radiation Oncology, Shandong University Cancer Center, Jinan, Shandong, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3Department of Radiation Oncology, Jinan Zhangqiu District People’s Hospital, Jinan, Shandong, People’s Republic of China; 4Department of Thoracic Surgery, Shandong University Cancer Center, Jinan, Shandong, People’s Republic of China; 5Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Shaoyu Hao, Department of Thoracic Surgery, Shandong University Cancer Center, Jinan, Shandong, China; Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University, and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China, Tel +86 13188870730, Email hshaoyu1985@126.comPurpose: This study aims to identify the most effective treatment approach and compares the survival rates, along with complications, in patients with locally resectable esophageal squamous cell carcinoma (ESCC) who were treated with one of the three treatment patterns: neoadjuvant chemotherapy followed by surgery (NCT+S), neoadjuvant chemoradiotherapy followed by surgery (NCRT+S), or surgery followed by chemoradiotherapy (S+CRT).Methods: We conducted a retrospective analysis of the medical records of ESCC patients who received one of these treatments between March 2015 and March 2022. This analysis aimed to identify differences in long-term survival, pathological responses, and complications across the three treatment groups. To address potential confounding factors, propensity score matching (PSM) and Cox proportional hazards models were utilized.Results: This study included a cohort of 715 patients: 197 in the NCT+S group, 188 in the NCRT+S group, and 330 in the S+CRT group, all meeting the selection criteria. After PSM, the median disease-free survival (DFS) time was 38.9 months, 25.6 months, and 15.3 months for NCRT+S, NCT+S, and S+CRT groups, respectively. There were statistically significant differences in the 5-year DFS and 5-year OS among the three groups (P=0.04 and P=0.02, post-matching, respectively). Notably, neoadjuvant therapy showed a correlation with increased postoperative anastomotic leakage rates (17.5% in NCRT+S, 10% in NCT+S, and 5% in S+CRT; P=0.03, post-matching), regardless of the PSM adjustment.Conclusion: The findings indicate that neoadjuvant therapy before surgery offers a significant survival advantage over postoperative adjuvant therapy for patients with locally advanced resectable ESCC. Despite similar safety profiles, neoadjuvant therapy appears to be associated with a higher incidence of anastomotic leakage after surgery.Keywords: neoadjuvant therapy, esophageal squamous cell carcinoma, postoperative adjuvant therapy, prognosis

Lin Zhang,1,2 Yunyue Liu,2 Jinping Tian2,3 1Department of Infectious Diseases, The Affiliated Suqian First People’s Hospital of Nanjing Medical University, Suqian, Jiangsu Province, People’s Republic of China; 2School of Nursing, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 3Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of ChinaCorrespondence: Jinping Tian, Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Gulou District, Nanjing, Jiangsu Province, 210000, People’s Republic of China, Tel +86 13851550156, Email tianjp6@163.comAbstract: Chronic hepatitis B (CHB) is a common chronic viral infectious disease that requires long-term treatment to control the condition and prevent complications. To standardize treatment regimens for CHB, professional associations have established relevant guidelines, but they have often overlooked patient preferences. Historically, in the treatment process, medical decisions were predominantly made by physicians or health care administrators, with limited patient involvement, leading to the neglect of patient preferences. Patient attitudes, expectations, and needs are all influenced by their preferences, and patient preferences have a direct impact on treatment adherence. Understanding and respecting patient preferences are crucial to ensuring treatment effectiveness. This article will explore patient preferences in the treatment of CHB and elucidate the influence of patient preferences on treatment adherence, aiming to provide insights for the development of a more personalized and effective health care process.Keywords: CHB, treatment options, patient preferences, adherence

Zhixing Xu,1,2,&ast; Haitao Xu,1,&ast; Xi Chen,1,&ast; Xiaobing Huang,1 Jintao Tian,1 Jinxi Zhao,1 Bohu Liu,1 Fengcai Shi,2 Jin Wu,2 Jun Pu1 1Department of Neurosurgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650223, People’s Republic of China; 2Department of Neurosurgery, The Pu’er People’s Hospital, Pu’er, 665000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jin Wu; Jun Pu, Email wujin20170907@163.com; pujun137@126.comBackground: The Coiled-coil domain-containing proteins (CCDCs) are expressed in many cancers, but the role of Coiled-coil domain-containing protein 103 (CCDC103) in cancers remains unclear. Further investigations are necessary to ascertain its diagnostic significance and understand its biological function in cancers. This study aims to elucidate the biological functionalities of CCDC103 in glioma and evaluate the correlation between CCDC103 expression with glioma progression.Methods: Clinical data on glioma patients were acquired from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and the Gene Expression Omnibus (GEO). The evaluation encompassed the examination of correlations between CCDC103 expression, pathological characteristics, and clinical outcomes. Furthermore, the analysis included the assessment of the correlations between CCDC103 expression and immune cell infiltration as well as glioma progression.Results: Gliomas have higher levels of CCDC103 expression than the para-carcinoma tissues. Poorer prognosis, unfavorable histological characteristics, the absence of IDH gene mutations, and the absence of chromosome 1p and 19q deletions were all associated with higher expression of CCDC103 in gliomas. In addition to patient age, tumor grade, the absence of IDH mutations, and the absence of chromosome 1p and 19q deletions, univariate and multivariate Cox analyses showed that CCDC103 expression was independently prognostic of overall survival, disease-free survival, and progression-free survival in patients with glioma. Furthermore, tumor infiltration of B cells, neutrophils, macrophages, and dendritic cells were all linked with elevated expression of CCDC103. High CCDC103 expression was linked to immune response-related signaling pathways and cell proliferation, according to gene set enrichment analysis (GSEA). Notably, the knockdown of CCDC103 in glioma cell lines resulted in a significant reduction in cell proliferation and migration.Conclusion: The correlation between CCDC103 expression and both glioma progression and immune cell infiltration implies that CCDC103 expression holds promise as a valuable prognostic biomarker for glioma.Keywords: glioma, CCDC103, prognosis, biomarker, immune infiltration

Ling Yang,1,2 Maolin Cao,3 Jing Tian,1 Peijin Cui,1 Ling Ai,3 Xue Li,4 Hua Li,5 Menghan Gao,1 Liang Fang,1,2,6 Libo Zhao,1,2 Fang Gong,2,6 Chanjuan Zhou1,3,4,6 1Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Cerebrovascular Disease Research, Chongqing, People’s Republic of China; 3Department of General Practice, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Central Laboratory, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 5Department of Ophthalmology, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 6Chongqing Clinical Research Center for Geriatric Disease, Chongqing, People’s Republic of ChinaCorrespondence: Fang Gong; Chanjuan Zhou, Yongchuan Hospital of Chongqing Medical University, No. 439 Xuanhua Road, Yongchuan, Chongqing, 402160, People’s Republic of China, Email 1512367841@qq.com; chanjuanzhou@hospital.cqmu.edu.cnPurpose: The quality of life of worldwide adolescents has been seriously affected by depression. Notably, the inflammatory response is closely associated with the pathophysiology of depression. The present study applied a novel targeted proteomics technology, Olink proximity extension assay (PEA), to profile circulating immune-related proteins in adolescents with depression.Methods: In the present study, the expression levels of 92 inflammation-related proteins were compared between adolescents with depression (ADs) (n=15) and healthy controls (HCs) (n=15), using the OLINK PEA inflammation panel. We further validated 5 top proteins that were identified through KEGG and GO analyses between 40 HCs and 50 ADs, including CCL4, CXCL5, CXCL6, CXCL11, and IL-18 using enzyme linked immunosorbent assay (ELISA).Results: We identified 13 differentially expressed proteins between the two cohorts, including 5 up-regulated and 8 down-regulated proteins. Among them, the TRAIL protein levels were significantly negatively correlated with the HAMA-14 score (r=− 0.538, p= 0.038), and the levels of transforming growth factor α (TGF-α) were significantly associated with a change in appetite (r = -0.658, p = 0.008). After validation by ELISA, CCL4, CXCL5, CXCL11, and IL-18 showed significant changes between ADs and HCs (p < 0.05), while CXCL6 showed an up-regulated tendency in ADs (p=0.0673). The pooled diagnostic efficacy (area under the curve [AUC]) of these five inflammation markers in clinical diagnosis for adolescent depression was 0.819 (95% CI: 0.735– 0.904).Conclusion: We report a number of inflammation-related plasma biomarkers, which uncover a potential involvement of chemokines, cytokines, and cytokine receptors in adolescent depression. Their roles in the pathophysiology of depression need to be further elucidated.Keywords: olink proximity extension assay, biomarkers, adolescent depression, inflammation

Xueqi Wan,&ast; Huan Zhang,&ast; Jinfan Tian,&ast; Peng Hao, Libo Liu, Yuquan Zhou, Jing Zhang, Xiantao Song, Changjiang Ge Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changjiang Ge; Xiantao Song, Email cjge1116@163.com; song0929@mail.ccmu.edu.cnAbstract: Atherosclerosis (AS), a category of cardiovascular disease (CVD) that can cause other more severe disabilities, increasingly jeopardizes human health. Owing to its imperceptible and chronic symptoms, it is hard to determine the pathogenesis and precise therapeutics for AS. A novel type of programmed cell death called ferroptosis was discovered in recent years that is distinctively different from other traditional cell death pathways in morphological and biochemical aspects. Characterized by iron overload, redox disequilibrium, and accumulation of lipid hydroperoxides (L-OOH), ferroptosis influences endothelial cells, vascular smooth muscle cells (VSMCs), and macrophages, as well as inflammation, partaking in the pathology of many cardiovascular diseases such as atherosclerosis, stroke, ischemia-reperfusion injury, and heart failure. The mechanisms behind ferroptosis are so sophisticated and interwoven that many molecules involved in this procedure are unknown. This review systematically depicts the initiation and modulation of ferroptosis and summarizes the contribution of ferroptosis to AS, which may open a feasible approach for target treatment in the alleviation of AS progression.Keywords: ferroptosis, iron overload, oxidation, lipid peroxidation, atherosclerosis