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Nuclear factor kappa-B(NF-κB), an intricate nuclear transcription factor, is ubiquitously present within the myriad tissues and cells of the human corpus, engaging in a multiplicity of biological processes such as the development of the immune system, immune responses, inflammatory reactions, angiogenesis, and tumorigenesis. Its cardinal role in the pathogenesis of ocular diseases is increasingly illuminated by its prevalence. Owing to the unique architecture of the ocular globe, burgeoning studies have identified the excessive activation or dysregulation of the NF-κB signaling pathway as intimately associated with the progression of a multitude of ocular conditions, including, but not limited to, cataracts, dry eye syndrome, and glaucoma. The modulation of NF-κB activation, by targeting it, offers a potent mechanism for regulating ocular inflammation and mitigating disease progression, holding promise as a potential therapeutic strategy for ophthalmic disorders. An in-depth examination of the NF-κB signaling pathway's role in ocular diseases not only enriches our comprehension of the underlying mechanisms of these ailments, but also lays a crucial foundation for the innovation of new treatment modalities. Therefore, this article endeavors to provide a compendious review of the regulatory effects exerted by the NF-κB signaling pathway in ophthalmic conditions throughout recent years.

AIM: To compare the effect of small-incision lenticule extraction(SMILE)with different corneal cap thicknesses on postoperative astigmatism and short-term visual quality of patients with myopic astigmatism.METHODS: A total of 54 patients(108 eyes)with myopic astigmatism who underwent SMILE from June 2020 to June 2022 in our hospital were selected for the prospective controlled study, and patients were randomly assigned into two groups, with 27 cases(54 eyes)each. The corneal cap thickness design was 110 μm for the group A and 120 μm for the group B, while other operation parameters were consistent. Additionally, the uncorrected visual acuity(UCVA), spherical equivalent(SE), stiffness parameter A1(SP-A1), visual quality and vector parameters at baseline, 1 d,1 wk and 1 mo after surgery were compared between two groups.RESULTS: There was a statistically significant difference in UCVA, SE, and SP-A1 between the two groups at various time points before and after surgery(all P0.05). The objective scattering index(OSI)of the group A was lower than that of the group B, while Strehl ratio(SR)of the group A was higher than that of the group B at 1 d after surgery(both P0.05).CONCLUSION: SMILE procedures with both 110 μm and 120 μm corneal cap thicknesses are safe and effective in correcting myopic astigmatism without affecting postoperative SE, astigmatism, SP-A1 or contrast visual acuity. Whereas 110 μm corneal cap thickness results in faster early postoperative visual recovery and better early visual quality than 120 μm.

Zhiyan Dai,1,* Chao Chen,2,3,* Ziyan Zhou,1,2 Mingzhen Zhou,1,2 Zhengyao Xie,1 Ziyao Liu,1 Siyuan Liu,1 Yiqiang Chen,1 Jingjing Li,1 Baorui Liu,2 Jie Shen1,2 1Department of Precision Medicine, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Oncology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Oncology, Jinling Hospital, Clinical College of Nanjing Medical University, Nanjing, 21002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Shen, Department of precision medicine, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China, Email shenjie2008nju@163.com Baorui Liu, Department of Oncology, Nanjing Drum Tower Hospital,Clinical College of Nanjing Medical University, 321 Zhongshan Road, Nanjing, 210008, People’s Republic of China, Email baoruiliu@nju.edu.cnBackground: Immune checkpoint inhibitor (ICI) therapy is a promising treatment for cancer. However, the response rate to ICI therapy in hepatocellular carcinoma (HCC) patients is low (approximately 30%). Thus, an approach to predict whether a patient will benefit from ICI therapy is required. This study aimed to design a classifier based on circulating indicators to identify patients suitable for ICI therapy.Methods: This retrospective study included HCC patients who received immune checkpoint inhibitor therapy between March 2017 and September 2023 at Nanjing Drum Tower Hospital and Jinling Hospital. The levels of the 17 serum biomarkers and baseline patients’ characters were assessed to discern meaningful circulating indicators related with survival benefits using random forest. A prognostic model was then constructed to predict survival of patients after treatment.Results: A total of 369 patients (mean age 56, median follow-up duration 373 days,) were enrolled in this study. Among the 17 circulating biomarkers, 11 were carefully selected to construct a classifier. Receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.724. Notably, patients classified into the low-risk group exhibited a more positive prognosis (P = 0.0079; HR, 0.43; 95% CI 0.21– 0.87). To enhance efficacy, we incorporated 11 clinical features. The extended model incorporated 12 circulating indicators and 5 clinical features. The AUC of the refined classifier improved to 0.752. Patients in the low-risk group demonstrated superior overall survival compared with those in the high-risk group (P = 0.026; HR 0.39; 95% CI 0.11– 1.37).Conclusion: Circulating biomarkers are useful in predicting therapeutic outcomes and can help in making clinical decisions regarding the use of ICI therapy.Keywords: hepatocellular carcinoma, predictive model, immunotherapy, machine learning

Objective To systematically analyze and identify key risk factors for postoperative pulmonary hemorrhage using a combination of the random forest (RF) model and traditional logistic regression analysis, so as to provide data support for clinical practice. Methods This study included patients who underwent needle biopsy of lung masses from January 2020 to December 2023 in the Department of Interventional Therapy, Cancer Hospital, Tianjin Medical University. There were 844 cases, including 387 males and 457 females, ranging in age from 39 to 82 years. Clinical data and puncture-related characteristics were collected, including tumor size, puncture depth, puncture angle, presence of emphysema, lesion location in the lung, body position during puncture, whether the puncture passed through the interlobar fissure, and the number of punctures. The RF model was used to rank the importance of all variables, identifying those with the highest predictive value. Subsequently, a multivariate logistic regression model was applied to the top-ranked important variables to further evaluate their independent impact on postoperative pulmonary hemorrhage. Results The RF model results showed that tumor size and puncture depth had the highest importance in predicting the risk of postoperative pulmonary hemorrhage. Multivariate logistic regression analysis further confirmed that smaller tumor size (HR:0.980, 95% CI:0.971-0.989, P

Yang Liu,1,* Chunan Wang,1,* Sitong Liu,1,* Hangzhan - Ma,2 Jiayun Xu,3 Kai Jiang,1 Ruitao Lu,4 Xintao Shuai,5 Jinming Wang,3 Zhong Cao1 1School of Biomedical Engineering, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Orthopedics, Panyu Hospital of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Department of Oral Implantology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, People’s Republic of China; 4Shenzhen International Institute for Biomedical Research, Shenzhen, Guangdong, People’s Republic of China; 5Nanomedicine Research Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhong Cao; Jinming Wang, Email caozhong@mail.sysu.edu.cn; wjinm@mail.sysu.edu.cnBackground: As a burgeoning cancer treatment modality, photothermal therapy (PTT) has shown robust anti-tumor effects. However, it still faces numerous challenges, such as triggering an inflammatory response and potentially increasing the risk of cancer recurrence. To address these concerns, integration of PTT with anti-inflammatory therapies presents a promising approach to enhance the efficacy of cancer treatment and meanwhile reduce the risk of recurrence.Methods: In this study, Gd3+ was first chelated with dopamine to create Gd-DA chelates, and then the mesoporous dopamine nanoparticles MX@Arg-Gd-MPDA (MAGM NPs) were synthesized by combining arginine (Arg) and the anti-inflammatory medication meloxicam (MX). The photothermal properties of MAGM NPs were then defined and examined; the in vivo MRI imaging effect, as well as MAGM NPs’ anti-cancer and anti-inflammatory efficiency, were tested in a mouse model of breast cancer.Results: The incorporation of Arg doping into MAGM NPs was intended to boost its photothermal conversion efficiency and reactive oxygen species (ROS) scavenging ability. Additionally, synergizing with the anti-inflammatory agent meloxicam (MX) within the nanoparticles aimed to enhance the anti-inflammatory effect following photothermal therapy. Furthermore, gadolinium ions (Gd3+) were chelated into the nanostructure to enable precise T1-T2 dual-mode magnetic resonance imaging (MRI) of the intratumor accumulation profile. This imaging capability was leveraged to guide the implementation of photothermal therapy. Animal experiments demonstrated that MAGM NPs exerted a notable anticancer effect in a 4T1 breast cancer mouse model, under the precise guidance of MRI.Keywords: magnetic resonance imaging, photothermal therapy, anti-inflammatory therapy, mesoporous polydopamine, cancer therapy

Zheng Wan,1 Tianyi Liu,1 Ning Xu,1 Wenhao Zhu,2 Xiaoyu Zhang,2 Qin Liu,1 Haifeng Wang,2 Honglei Wang1 1Department of Neurovascular Surgery, The First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China; 2Department of Neurotrauma, The First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of ChinaCorrespondence: Haifeng Wang; Honglei Wang, Email hfwang@jlu.edu.cn; wanghongl@jlu.edu.cnIntroduction: Extracellular vesicles (EVs) are nanosized membrane vesicles that are naturally secreted by almost all cells and have gained considerable attention. Many studies have applied EVs to the treatment of brain diseases and validated their effectiveness. Although only a few EVs can penetrate the blood‒brain barrier (BBB) into the brain after administration, it has been proven that EVs and their cargos exert their effects by interacting with brain cells. PKH dyes are commonly used to stain EVs for distribution studies. However, systematic investigations of imaging characteristics of the PKH-labeled EVs distributed in the brain are still scarce.Methods: We stained EVs derived from mesenchymal stem cells with PKH26 or PKH67. PKH26-labeled EVs and PKH67-labeled EVs were administered at the same time into each mouse while PKH26-labeled EVs were given through tail veins and PKH67-labeled EVs were given through intraperitoneal injection. Confocal microscopy was used to explore the distribution difference of two types of EVs given via different routes in the brain.Results: The fluorescence of PKH26 and PKH67 had nearly identical distributions in brain slices after 1 h, 6 h, 12 h and 1 day of EV administration. Under the same confocal parameters, brain slices without EVs administration demonstrated the same result. However, liver slices from mice administered with labeled EVs showed obviously different distributions of two types PKH fluorescence.Discussion: These findings raise questions about the ability of PKH dyes as labels for EVs when explore the EV brain distribution observed via confocal microscopy.Keywords: extracellular vesicles, PKH dyes, brain distribution

Runing Fu,1,* Wenping Lian,1,* Bohao Zhang,2,* Gang Liu,3 Xinyu Feng,1 Yingjie Zhu,1 Jiuan Zhou,1 Xinyu Zhang,4 Shukai Wang,1 Huijuan Huo,1 Daxin Wang,1 Cui Liu,1 Saisai Gao,1 Yajie Ma,4 Mengle Peng1,* 1Department of Clinical Laboratory, The Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, People’s Republic of China; 3The Center of Meige Syndrome, The Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China; 4Department of Medical Affair, the Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mengle Peng; Yajie Ma, Email pengmengle1990@126.com; szsyywk@sina.comPurpose: Inflammatory markers are known to be associated with many diseases, but their role in Meige syndrome (MS) remains unclear. This study aimed to develop and validate a nomogram for the risk prediction of MS based on inflammatory markers.Patient Data and Methods: Data from 448 consecutive patients with MS at the Third People’s Hospital of Henan Province between January 2022 and December 2023 were retrospectively reviewed. The MS cohort was randomly divided into separate training and validation sets. A nomogram was constructed using a multivariate logistic regression model based on data from the training set. The model’s performance was validated through cross-validation, receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA).Results: A total of five predictors, including red blood cell distribution width (RDW), hemoglobin (HGB), high-density lipoprotein cholesterol (HDL-C), the lymphocyte-to-monocyte ratio (LMR), and the systemic immune‐inflammation index (SII), were identified using multivariate logistic regression from a total of 11 variables. The cross-validation results indicated the stability of the model constructed with the above five predictors. The model showed moderate predictive ability, with an area under the ROC curve of 0.767 in the training set and 0.735 in the validation set. The calibration curve and DCA results indicate that the model has strong consistency and significant potential for clinical application.Conclusion: We constructed a nomogram based on five risk predictors, RDW, HGB, HDL-C, the LMR and the SII, to predict MS and enhance the predictive accuracy for identifying MS risk.Keywords: Meige syndrome, inflammatory marker, nomogram, LMR, SII

Peng Liu,1,2,&ast; Tingting Lv,1,&ast; Yuanwei Liu,1,&ast; Xiaofei Zhang,1 Fei She,1 Rong He,1 Dan Li,1 Lianfeng Liu,1 Ping Zhang1 1Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of China; 2Department of Cardiology, Ordos Central Hospital, Ordos School of Clinical Medicine, Inner Mongolia Medical University, Inner Mongolia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Zhang, Email zhpdoc@126.comObjective: Atrial fibrillation (AF) is known to increase the risk of thromboembolic events and major adverse cardiovascular events (MACE). The impact of paroxysmal atrial tachycardia (PAT) on these risks remains unclear.Methods: This retrospective cohort study was conducted involving 889 patients diagnosed with PAT and 1106 control patients without PAT, all of whom underwent their initial 24-hour ECG monitoring between 2015 to 2020. Kaplan–Meier survival analysis and Cox regression analysis were used to evaluate the association between PAT and the study endpoints, including thromboembolic events and MACE.Results: Over a mean follow-up period of 50.3 months, the incidence of thromboembolic events and MACE was significantly higher in the PAT group compared to the control group (6.5% vs 1.7% and 19.1% vs 9.9%, respectively). After adjusting for common risk factors and baseline imbalances, the PAT group exhibited a significantly elevated risk of thromboembolic events (hazard ratio [HR] 3.782, 95% confidence interval [CI] 2.212– 6.467; P < 0.001) and MACE (HR 1.795, 95% CI 1.398– 2.305; P < 0.001). However, the frequency of PAT episodes, heart rate, and maximum heart rate were not significantly associated with these outcomes. Within the PAT group, a history of stroke, transient ischemic attack, and chronic renal failure were identified as independent risk factors for thromboembolic events, while hypertension, coronary heart disease, heart failure, and chronic renal failure were independently associated with MACE.Conclusion: PAT, as detected by 24-hour dynamic ECG, is associated with an increased risk of thromboembolic events and MACE.Keywords: paroxysmal atrial tachycardia, thromboembolic events, ischemic stroke, transient ischemic attack, systemic thromboembolism, major adverse cardiovascular events

Shengfeng Liu,1,2 Jian Liu,1,2 Xueni Cheng,1 Dahai Fang,1 Xiaolu Chen,1 Xiang Ding,1 Xianheng Zhang,1 Yiming Chen1 1Department of Rheumatology, the First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui Province, People’s Republic of China; 2Anhui Key Laboratory of Application and Development of Internal Medicine of Modern Chinese Medicine, Anhui University of Chinese Medicine, Hefei, Anhui Province, People’s Republic of ChinaCorrespondence: Jian Liu, Department of Rheumatology, the First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui Province, People’s Republic of China, Tel +86 13955109537, Email liujianahzy@126.comAbstract: Rheumatoid arthritis (RA) is a chronically progressive autoimmune disease with increasing age-standardized prevalence and incidence of RA worldwide. Its pathological features are persistent synovitis of the joint, accompanied by the release of a large number of inflammatory cytokines and cartilage and bone destruction. RA can lead to progressive joint damage, stiffness and swelling, vascular and bone-related complications, and irreversible disability, which seriously affects patients’ life treatment. Early diagnosis and treatment can enhance the quality of life of RA patients. Platelet-to-lymphocyte ratio (PLR), as a common indicator in routine blood tests, has been proposed as an indicator of systemic inflammation in recent years. Its clinical detection is less invasive, economical, rapid and simple, and has been applied to the clinical evaluation of a variety of diseases. Of note, this indicator is important in assessing disease activity in RA, co-diagnosing RA, detecting subclinical complications, and monitoring responses to anti-inflammatory therapy. Therefore, this review summarizes the relationship between PLR and RA and the relevant mechanisms, further advancing the understanding of the clinical value of PLR.Keywords: platelet-to-lymphocyte ratio, rheumatoid arthritis, inflammatory, blood platelets, lymphocytes

Yuxuan Yao,1– 3 Hong Zhao,4 Hua Lu,5 Xiaoli Liu,6 Hui Liu,7 Zhanli Fu,8 Chunyue Li,1 Fude Zhou,1– 3 Wanyin Hou,1– 3 Sufang Shi1– 3 1Department of Nephrology, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, People’s Republic of China; 2Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People’s Republic of China; 3Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, People’s Republic of China; 5Department of Nephrology, Xingtai People’s Hospital, Xingtai, Hebei, People’s Republic of China; 6Department of Pathology, Xingtai People’s Hospital, Xingtai, Hebei, People’s Republic of China; 7Department of Pathology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 8Department of Nuclear Medicine, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Wanyin Hou; Hong Zhao, Peking University First Hospital, Xicheng District, Beijing, People’s Republic of China, Tel +86 10-83575685, Email helenwanyin@bjmu.edu.cn; zhaohong_pufh@bjmu.edu.cnAbstract: Q fever, an infectious zoonotic disease caused by Coxiella burnetii, remains prevalent in China. Systemic infections can result in renal or hepatic complications; however, it is rare for both the kidneys and liver to be simultaneously affected. We present a case of a patient who exhibited fever, rapid deterioration in renal function, thrombocytopenia, and severe ascites. Renal biopsy revealed crescentic glomerulonephritis, while liver biopsy demonstrated non-cirrhotic portal hypertension. Metagenomic next-generation sequencing (mNGS) identified the presence of Coxiella burnetii in both venous blood and liver tissue samples. Notably, the patient’s renal insufficiency and ascites showed a positive response to treatment for chronic Q fever. These findings provide valuable insights into the limited understanding of kidney and liver diseases associated with Q fever. Advanced diagnostic technologies, including mNGS and positron emission tomography/computed tomography (PET/CT), have been employed to identify Coxiella burnetii infection.Keywords: Coxiella burnetii, acute kidney injury, non-cirrhotic portal hypertension, biopsies

Wenyi Li,1,2 Zhenguo Liu,1 Min Song,1 Zhenpeng Shi,1 Jihang Zhang,3 Junyu Zhou,1 Yidan Liu,1 Yun Qiao,4 Deshan Liu4 1First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 2Research Center for Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 3Traditional Chinese Medicine College, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 4Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Deshan Liu, Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China, Tel +86 18560087381, Email liudeshan@sdu.edu.cnContext: Diabetic nephropathy (DN) and cognitive dysfunction (CD) are common complications of diabetes. Yi-Qi-Bu-Shen Recipe (YQBS) can effectively reduce blood glucose, improve insulin resistance, and delay the progression of diabetic complications. The underlying mechanisms of its effects need to be further studied.Objective: This study elucidates the mechanism of YQBS in DN with CD through network pharmacology and experimental validation.Materials and Methods: Protein-protein interaction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Male Sprague-Dawley (SD) rats were divided into 6 groups: model, YQBS (2, 4, 8 g/kg), positive control (metformin, 200 mg/kg), and control; the DN model was established by high sugar and high fat diet combined with intraperitoneal streptozotocin injection. After the DN model was established, the rats were gavaged for 10 weeks. Serum, kidneys, and hippocampus tissues were collected to measure the expression levels of TLR4, NF-κB, TNF-α, and IL-6.Results: The network pharmacology analysis showed that quercetin and kaempferol were the main active components of YQBS. TNF and IL-6 were the key targets, and TLR4/NF-κB pathway was crucial to YQBS in treating DN complicated with CD. Experimental validation showed that the intervention of YQBS can reduce TNF-α and IL-6 in serum, and also significantly decreases the protein expression of TLR4 and NF-κB.Conclusion: YQBS exerts anti-inflammatory effects on DN with CD through TLR4/NF-κB pathway. This study provides a biological basis for the scientific usage of YQBS in inflammation diseases and supplies experimental evidence for future traditional Chinese medicine development.Keywords: Yiqi Bushen Recipe, diabetes nephropathy, cognitive dysfunction, network pharmacology, inflammation

BackgroundsInsomnia is frequent in schizophrenia and is found to be negatively affected by stressful life events， psychotic symptoms and depressive disorder， while the relationship among the four remains understudied in community-dwelling patients with schizophrenia.ObjectiveTo analyze the effect of stressful life events on insomnia in community-dwelling patients with schizophrenia， and to explore the mediation effect of psychotic symptoms and depression， so as to provide references for the intervention of insomnia in community-dwelling patients with schizophrenia.MethodsFrom April to June 2023， a sample of 1 105 patients with schizophrenia attending 48 community health centers in Chengdu， Sichuan province and fulfilling the International Classification of Diseases， tenth edition （ICD-10） diagnostic criteria were included. All subjects were assessed using Stressful Life Event Scale （SLEs）， Athens Insomnia Scale （AIS）， Psychosis Screening Questionnaire （PSQ）， and Patient Health Questionnaire Depression Scale （PHQ-9）. Spearman correlation analysis was used to determine the correlation among the scales. Then the mediation model was constructed using Smart PLS 4.0， and tested with partial least squares algorithm and Bootstrap techniques.Results332 patients （30.05%） with community schizophrenia were found to have insomnia. AIS scores in patients with schizophrenia were positively correlated with the scores on SLEs， PSQ and PHQ-9 （r=0.165， 0.322， 0.554， P

Zhihong Liu,1,2,&ast; Xiaofang Liang,1,&ast; Yu Zhang,1 Wenbo Deng,1 Yulin Wang,3 Zhangping Lu,2 Qianqian Liu,2 Lianhua Wei2 1School of Public Health, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, People’s Republic of China; 2Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, Gansu, People’s Republic of China; 3Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lianhua Wei, Email 107306723@qq.comAbstract: The development of antibiotic resistance complicates the treatment of infectious diseases and is a global public health threat. However, drug repurposing can address this resistance issue and reduce research and development costs. Niclosamide is a salicylanilide compound approved by the Food and Drug Administration (FDA), and it has been used clinically for treating parasitic infections for many years. Recent studies have shown that niclosamide can inhibit bacterial and fungus activity by affecting the quorum sensing system, biofilm formation, cell membrane potential, and other mechanisms. Here, we discuss recent advances in the antimicrobial applications of niclosamide and its derivatives to provide new perspectives in treating infectious diseases.Keywords: antimicrobial resistance, multi-drug resistance, niclosamide, a derivative, drug repurposing

Qian Cheng,1 Yishu Tang,2 Jing Liu,1 FeiYang Liu,1,&ast; Xin Li1,&ast; 1Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Emergency, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: FeiYang Liu; Xin Li, Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China, Tel +86-731-88618814 (88618214) ; Tel +86-731-88618814 (88618214), Email 546917399@qq.com; lixiner1975@163.comObjective: The role of chest computed tomography (CT) in distinguishing the causative pathogens of pulmonary infections in patients with hematological malignancies (HM) is unclear. The aim of our study was to compare and assess the clinical characteristics, radiologic features and potential differential diagnostic value of CT in HM patients and other different immune statuses patients with pulmonary infections.Methods: Patients were divided into immunocompetent (105 cases) and immunocompromised groups (99 cases) according to immune status. Immunocompromised patients included the HM group (63 cases) and the non-HM group (42 cases). The basic clinical data and CT findings were collected and statistically analyzed.Results: Regarding the pathogen distribution, viral, Pneumocystis jirovecii and mixed infections were more common in the immunocompromised group than the immunocompetent (p < 0.01), but viral infections were more common in the HM group than in the non-HM group (p=0.013). Immunocompromised patients had more diverse CT findings and more serious lesions (mostly graded 2– 4) than immunocompetent patients. The most common CT findings in HM patients were consolidation and ground-glass opacities (GGO), which were also found in the non-HM group. The overall diagnostic accuracy of CT was lower in immunocompromised patients than in immunocompetent patients (25.7% vs 50.5%, p< 0.01). CT had better diagnostic efficacy for fungi and Pneumocystis jirovecii in HM patients.Conclusion: CT diagnosis is less efficient in distinguishing the causative pathogens of HM patients. However, CT can help distinguish fungal pneumonia and Pneumocystis jirovecii pneumonia in HM patients.Clinical Relevance Statement: Our study might facilitate clinical decision-making in fungal pneumonia and Pneumocystis jirovecii pneumonia in HM patients.Keywords: pneumonia, hematological malignancies, computed tomography, diagnostic value

Xiao Shen,1 Jin-Xing Zhang,1 Jin Liu,2 Sheng Liu,1 Hai-Bin Shi,1 Yuan Cheng,3 Qing-Qiao Zhang,4 Guo-Wen Yin,5 Qing-Quan Zu1 1Department of Interventional Radiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 2Department of Clinical Medicine Research Institution, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 3Department of Medical Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, People’s Republic of China; 4Department of Interventional Radiology and Vascular Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, People’s Republic of China; 5Department of Interventional Radiology, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, People’s Republic of ChinaCorrespondence: Qing-Quan Zu, Department of Interventional Radiology, The First Affiliated Hospital with Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel +86-13913807470, Fax +86-25-83724440, Email zuqingquan@njmu.edu.cnPurpose: Transarterial chemoembolization (TACE), when used in combination with immunotherapy and antiangiogenic therapy, has been shown to have synergistic anticancer effects. The aim of this study was to further assess the efficacy and safety of TACE combined with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC) in the real world.Methods: Between August 2021 and September 2023, clinical information was collected from consecutive HCC patients who received treatment via TACE-Atezo/Bev at four tertiary institutions. This study evaluated the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) as outcomes. Predictors for OS and PFS were also analyzed. Treatment-related adverse events (TRAEs) were recorded and assessed.Results: Ninety-two patients were enrolled in this study, with a median follow-up duration of 14.1 months. The ORRs based on the modified Response Evaluation Criteria in Solid Tumors (RECIST) and RECIST 1.1 criteria were 54.3% and 41.3%, respectively. The median OS and PFS of the patients were 15.9 months [95% confidence interval (CI), 14.5– 17.2 months] and 9.1 months (95% CI, 7.4– 10.8 months), respectively. Multivariate analyses revealed that the Eastern Cooperative Oncology Group score and neutrophil‒lymphocyte ratio were independent risk factors for OS, whereas tumor size and extrahepatic metastasis were independent risk factors for PFS. Grade 3/4 TRAEs occurred in 16.3% (15/92) of the patients and were controlled conservatively.Conclusion: The combination of Atezo/Bev with TACE demonstrated acceptable synergistic therapeutic effects and manageable safety profiles in patients with unresectable HCC.Keywords: atezolizumab, bevacizumab, efficacy, hepatocellular carcinoma, transarterial chemoembolization

Weiqian Zhang,1,&ast; Shuiying Chen,1,&ast; Zhongyu Bai,1 Menglai Gan,2 Mingwei Chen,2 Ying Zhang,1 Sai Liu,2 Dongjuan Liu1 1Department of Emergency and Oral Medicine, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, Liaoning, People’s Republic of China; 2Department of Dental Materials, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongjuan Liu, Department of Emergency and Oral Medicine, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, No. 117 Nanjing North Street, Heping District, Shenyang, Liaoning, 110002, People’s Republic of China, Email dongjuanliu@cmu.edu.cn Sai Liu, Department of Dental Materials, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, No. 117 Nanjing North Street, Heping District, Shenyang, Liaoning, 110002, People’s Republic of China, Email liusai@cmu.edu.cnAbstract: Oral squamous cell carcinoma (OSCC) is the most prevalent and deadly malignancy of the head and neck. The standard treatments for OSCC are surgery, radiotherapy, and chemoradiotherapy, which can cause severe cosmetic and functional damage to the oral cavity and impair the patients’ quality of life. Photodynamic therapy (PDT) is a promising alternative that uses light-activated photosensitizers to induce selective phototoxicity and necrosis in the target tissues. PDT has several advantages over conventional treatments, such as minimal invasion, low side effects, high selectivity and preservation of the oral function and appearance. This review explores the principles, mechanisms, and current applications of PDT for OSCC. We address the challenges, such as the depth of light penetration and tissue hypoxia, and underscore the progressive innovations in photosensitizer enhancement, nanotechnological integration, and precision therapy. The exploration of biomarkers for refining patient selection and tailoring individualized treatment regimens is also undertaken. PDT holds promise as a secure and efficacious modality for OSCC management. Nonetheless, additional investigation is imperative to refine treatment protocols and validate sustained therapeutic success. Keywords: oral squamous cell carcinoma, photodynamic therapy, photosensitizers, nanotechnology, biomarkers

Jiamin Mao,1,2 Xiaoyuan Liu,2 Lie Zhang,1 Yu Chen,2 Shiyu Zhou,2 Yujiao Liu,2 Jing Ye,2 Xiaohong Xu,2 Quan Zhang1– 4 1Department of Neurosurgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, People’s Republic of China; 2Sichuan Higher Education Institute Key Laboratory of Structure-Specific Small Molecule Drugs, Institute of Materia Medica, School of Pharmacy, Chengdu Medical College, Chengdu, 610500, People’s Republic of China; 3Development and Regeneration Key Laboratory of Sichuan Province, Department of Anatomy and Histoembryology, Chengdu Medical College, Chengdu, 610500, People’s Republic of China; 4Chengdu Nature’s Grace Biological Technology Co., Ltd., Chengdu, 610213, People’s Republic of ChinaCorrespondence: Quan Zhang, Email zhangquancdmc@126.comPurpose: Acute alcohol intoxication (AAI) is a life-threatening medical condition resulting from excessive alcohol consumption. Our research revealed the potential of morin (MOR) in treating AAI. However, MOR’s effectiveness against AAI was hindered by its poor solubility in water and low bioavailability. In this study, our aim was to develop a self-nanoemulsifying drug delivery system (SNEDDS) to enhance MOR’s solubility and bioavailability, evaluate its anti-AAI effects, and investigate the underlying mechanism.Methods: The composition of MOR-loaded self-nanoemulsifying drug delivery system (MOR-SNEDDS) was determined by constructing pseudo-ternary phase diagrams, and its formulation proportion was optimized using the Box-Behnken design. Following characterization of MOR-SNEDDS, we investigated its pharmacokinetics and biodistribution in healthy animals. Additionally, we assessed the anti-AAI effects and gastric mucosal protection of MOR-SNEDDS in an AAI mice model, exploring potential mechanisms.Results: After breaking down into tiny droplets, the optimized mixture of MOR-SNEDDS showed small droplet size on average, even distribution, strong stability, and permeability. Pharmacokinetic studies indicated that MOR-SNEDDS, compared to a MOR suspension, increased the area under the plasma concentration-time curve (AUC0-t) by 10.43 times. Additionally, studies on how drugs move and are distributed in the body showed that MOR-SNEDDS had an advantage in passively targeting the liver. Moreover, in a mouse model for alcohol addiction, MOR not only decreased alcohol levels by boosting the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the stomach and liver, which counteracted the loss of righting reflex (LORR), but also reduced alcohol-induced damage to the stomach lining by lowering malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) levels. Furthermore, MOR-SNEDDS notably amplified these effects.Conclusion: MOR exhibits significant potential as a new medication for treating AAI, and utilizing MOR-SNEDDS with high oral bioavailability represents a promising new strategy in combating AAI.Keywords: Morin, self-nanoemulsifying drug delivery system, acute alcohol intoxication, oral bioavailability, alcohol-induced tissue injury

Junmei Fan,1,&ast; Jinghui Zhao,2,&ast; Junkun Zhang,3 Yanhua Chen,1 Xingyu Bi,1 Huiping Liu,1 Junfen Liu,1 Jinbao Wang,1 Xueqing Wu1 1Department of Reproductive Medicine Center, Children’s Hospital of Shanxi and Women Health Center of Shanxi, Taiyuan, Shanxi, 030013, People’s Republic of China; 2Department of Pediatric and Adolescent Gynecology, Shenzhen Children’s Hospital, Shenzhen, Guangdong, 518000, People’s Republic of China; 3Department of Intensive Care Unit, Shanxi Bethune Hospital, The Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xueqing Wu, Department of Reproductive Medicine Center, Children’s Hospital of Shanxi and Women Health Center of Shanxi, 13th Xinmin North Street, Xinghualing District, Taiyuan, Shanxi, 030013, People’s Republic of China, Tel +86 351 3360725, Email xueqingw_wu95@163.comBackground: This study aimed to explore the effect of vitamin D supplementation on lymphocyte subsets in infertile women.Methods: The study involved a total of 247 patients who suffered recurrent embryo implantation failure (RIF) or recurrent spontaneous abortion (RSA) between January and December 2019 in the Reproductive Medicine Center of Children’s Hospital of Shanxi and Women Health Center of Shanxi. The differences in the vitamin D and lymphocyte subsets of the two diseases, the correlation between the 25-hydroxy vitamin D and lymphocyte subsets, the changes in the lymphocyte subsets after vitamin D supplementation and the impact on pregnancy outcome were analysed.Results: The prevalence of vitamin D deficiency was 77.33% (191/247). After vitamin D supplementation, there were no significant differences in helper T cells (Th), cytotoxic T cells (Tc), Th/Tc and natural killer cells (NK) (p > 0.05), but there were significant differences in leukocyte differentiation antigens 3+ (CD3+), natural killer T cells (NKT), B lymphocytes and vitamin D (p < 0.05). Before vitamin D supplementation, the difference in the composition ratio of different vitamin D levels between the RIF and RSA groups was not statistically significant. At different vitamin D levels, there were no significant differences in CD3+, Th, Tc, Th/Tc, NK or B lymphocyte (p > 0.05), but there was a significant difference in NKT (p < 0.05).Conclusion: Vitamin D supplementation can reduce the level of NKT in infertile women, which may be of benefit to the pregnancy outcome of couples who experience RIF.Keywords: recurrent embryo implantation failure, infertility, lymphocyte subsets, recurrent spontaneous abortion, vitamin D

Abstract Background With the improvement of anastomotic techniques and the iteration of anastomotic instruments, robotic intracorporeal suturing has become increasingly proficient. The era of fully intracorporeal anastomosis in robotic gastric cancer resection is emerging. This study aims to explore the impact of totally robotic distal gastrectomy (TRDG) and robotic-assisted distal gastrectomy (RADG) on patients’ quality of life. Patients and methods This study is a comparative retrospective study of propensity score matching. This study included 306 patients who underwent robotic distal gastrectomy for gastric cancer between June 2016 and December 2023 at our center. Covariates used in the propensity score included sex, age, BMI, ASA score, maximum tumour diameter, degree of histological differentiation, Pathological TNM stage, Pathological T stage, Pathological N stage, and Lauren classification. Outcome measures included operative time, intraoperative bleeding, time to first venting, time to first fluid intake, postoperative hospital stay, total hospitalization cost, total length of abdominal incision, postoperative complications, inflammatory response, body image, and quality of life. Results According to the results of the study, compared with the RADG group, the TRDG group had a faster recovery time for gastrointestinal function (P = 0.025), shorter length of abdominal incision (P

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

Siqi Liu, Xin Sun, Na Liu, Fangcai Lin Department of Breast Surgery, Beijing Electric Power Hospital, Beijing, 100071, People’s Republic of ChinaCorrespondence: Fangcai Lin, Beijing Electric Power Hospital, Beijing, 100071, People’s Republic of China, Email bjdltgyx@163.comBackground: Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an RNA-binding protein with N6-methyladenosine (m6A) reader function, is associated with the poor prognosis of various tumors, including triple-negative breast cancer (TNBC). Small nuclear ribonucleoprotein D1 polypeptide (SNRPD1), a spliceosome member, exerts diagnostic and therapeutic functions in breast cancer by regulating the cell cycle and is a potential therapeutic target. However, the interaction between IGF2BP2 and SNRPD1 in the progression of TNBC remain unclear.Objective: This study aimed to investigate the interaction between IGF2BP2 and SNRPD1 in TNBC and elucidate the underlying mechanisms.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression levels of SNRPD1 and IGF2BP2 in human normal breast cells (MCF10A) and TNBC cells (MDA-MB-231). MDA-MB-231 cells were transfected with SNRPD1 interference or overexpression vectors, or co-transfected with SNRPD1 interference and IGF2BP2 overexpression vectors simultaneously. Cell viability, apoptosis, and invasion were assessed using MTT, flow cytometry, and Transwell assays. RNA stability, m6A levels, and the interaction between SNRPD1 and IGF2BP2 were evaluated using qRT-PCR, methylated RNA immunoprecipitation, and RIP assays.Results: SNRPD1 was significantly up-regulated in TNBC cells, promoting cell viability and invasion while inhibiting apoptosis. IGF2BP2 was also up-regulated in TNBC cells and enhanced SNRPD1 mRNA stability via m6A modification. Furthermore, IGF2BP2 overexpression reversed the anti-tumor effect of SNRPD1 knockdown.Conclusion: IGF2BP2 and SNRPD1 were significantly highly expressed in TNBC cells. IGF2BP2 might enhance the stability and protein expression of SNRPD1 through m6A-dependent mechanisms, potentially contributing to the progression of TNBC.Keywords: triple-negative breast cancer, IGF2BP2, SNRPD1, m6A-dependent

Bin Liu,&ast; Bingtian Zhao,&ast; Yan Yin, Yan Jiang, Xue Feng, Lei Wang, Liang Zhai, Guangxin Liu, Dongsheng Shi, Jianwen Qin Department of Respiratory and Critical Medicine, Tianjin Chest Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongsheng Shi; Jianwen Qin, Tianjin Chest Hospital, No. 261, Taierzhuang South Road, Jinnan District, Tianjin, 300051, People’s Republic of China, Email shi_ds@126.com; qinjianwen2005@aliyun.com; 5020200603@nankai.edu.cnPurpose: DNA methylation plays a regulatory role in the oncogenesis and tumor progression and is valuable in the diagnosis and prognosis of cancer. While circulating tumor DNA (ctDNA) is widely used in the detection of oncogenic mutations and the guidance of treatment in advanced non-small cell lung cancer (NSCLC), studies of ctDNA methylation remains insufficient. We aim to investigate the methylation profiles of ctDNA in patients with advanced NSCLC undergoing EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy and to discover novel biomarkers with predictive or prognostic value.Patients and Methods: We recruited 49 patients with EGFR-mutated advanced NSCLC undergoing EGFR-TKI as first-line treatment. Utilizing next-generation sequencing, we examined the somatic mutations and methylation signatures within the tumor-associated genomic regions of ctDNA from pre-treatment blood. Subsequently, we explored the association of these molecular features with the patients’ response to therapy and their progression-free survival (PFS).Results: Genomic mutation profiling revealed no significant association of PFS or best overall response (BOR) and ctDNA status. Evaluation of ctDNA methylation showed a negative correlation between the methylation of small nucleolar RNA (snoRNA) genes and PFS (R=− 0.31, P=0.043). Furthermore, high-level methylation of SNORD3F was associated with poorer PFS (mPFS 346d vs 243d, HR 0.49, 95% CI 0.24– 0.93, P=0.029).Conclusion: Our study explored the prognostic value of ctDNA methylation in patients with advanced NSCLC undergoing targeted therapies and first revealed the predictive role of SNORD3F.Keywords: ctDNA, EGFR, DNA methylation, lung cancer, snoRNA, SNORD3F

XingYun Liu,1,&ast; JingDuo Zhao,2,&ast; FuRong Liu,1 ZhiZhong Xie,2 XiaoYong Lei,2 Zhe Wang,3 Zerui Yang,4 YuSheng Zhou,1,3 GuoTao Tang2 1The Affiliated Nanhua Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China; 2Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, People’s Republic of China; 3The Second Affiliated Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China; 4NMPA Key Laboratory for Technology Research and Evaluation of Pharmacovigilance, Guangdong Pharmaceutical University, Guangzhou, 510086, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: YuSheng Zhou, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China, Email yszhou08@126.com GuoTao Tang, Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang Medical School, Hengyang, Hunan, 421001, People’s Republic of China, Email tgtzq@163.comBackground: Breast cancer treatment has been a global puzzle, and targeted strategies based on the hypoxic tumor microenvironment (TME) have attracted extensive attention. As a signature transcription factor overexpressed in hypoxia tumor, hypoxia-inducible factor-1 (HIF-1) contribute to cancer progression. Compound 7-(3-(2-chloro-1H-benzo[d]1midazole-1-yl) propoxy)-2-(3,4,5-trime-thoxyphenyl)-4H-chromen-4-one, synthesized and named FB15 in our earlier research, a potential inhibitor of HIF-1α signaling pathway, has been proved a promising drug candidate for many kinds of cancer chemotherapy. However, the poor solubility and undesirable pharmacokinetics of FB15 leads to limited treatment efficacy of tumor, which ultimately restricts its potential clinical applications. Carbonic anhydrase IX (CAIX), a tumor cell transmembrane protein, was overexpressed in hypoxia tumor site. Acetazolamide (AZA), a highly selective ligand targeting CAIX, can be utilized to delivery FB15 to hypoxia tumor site.Methods: In this study, we prepared and characterized FB15 loaded nano-mixed micelles with the AZA conjugated poloxamer 188 (AZA-P188) and D-a-Tocopherol Polyethylene 1000 Glycol Succinate (TPGS), denoted as, AZA-P188/TPGS@FB15. Its delivery efficiency in vitro and in vivo was assessed by in vitro drug release, cytotoxicity assay, cellular uptake, and in vivo pharmacokinetics and fluorescence imaging. Finally, therapeutic effect of AZA-P188/TPGS@FB15 was investigated using a preclinical breast cancer subcutaneous graft model in vivo.Results: In vitro studies revealed that AZA-P188/TPGS@FB15 could efficiently target breast cancer cells mediated by CAIX receptor, trigger FB15 release in response to acidic condition, and enhance cellular uptake and cytotoxicity against breast cancer cells. The pharmacokinetic studies showed that FB15-loaded AZA-functionalized micelles exhibited significantly increased AUC0-t over free FB15. In vivo imaging demonstrated that AZA-functionalized micelles significantly increased the drug distribution in the tumor site. In vivo experiments confirmed that AZA-P188/TPGS@FB15 exhibited superior inhibition of tumor growth in nude mice with good biosafety.Conclusion: AZA-P188/TPGS@FB15 hold promise as a potentially effective therapeutic way for breast cancer. Its targeted delivery system utilizing AZA as a carrier shows potential for improving the efficacy of FB15 in cancer therapy.Keywords: carbonic anhydrase IX-targeting, FB15, hypoxia inducible factor-1, nano-mixed micelles, pH-responsive

Bohao Dai,1,&ast; Xiaorong Peng,1,&ast; Jia Sun,1 Xueling Zhu,1 Xiang Liu,1 Ye Xiong,1 Zhikai Wan,1 Dairong Xiang,1 Jiangjin Hui,1 Chenxi Ying,2 Huiting Liu,1 Biao Zhu1,&ast; 1The Department of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Cardivascular Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Biao Zhu, The Department of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qing Chun Road, Hangzhou, 310006, People’s Republic of China, Email zhubiao1207@zju.edu.cnBackground: HIV-1 CRF01_AE is becoming the predominant HIV-1 subtype among patients in China. The distribution and characteristics of transmission clusters of HIV-1 CRF01_AE in Zhejiang, Eastern China remains unclear. This study analyzed the epidemiologic characteristics and transmission clusters of HIV-1 CRF01_AE in Zhejiang.Methods: Plasma samples obtained from 152 patients of HIV-1 CRF01_AE not undergoing ART were used to amplify HIV-1 pol and env gene. CRF01_AE drug resistance mutations (DRM) prevalence was analysed using Stanford University’s HIV Drug Resistance Database. A phylogenetic tree was constructed using FastTree (version 2.1.11) based on the GTR nucleotide substitution model and visualized using Figtree (version 1.4.4) and The Interactive Tree of Life; the Chinese HIV Gene Sequence Data Platform was used to construct genetic transmission networks.Results: Majority samples could be grouped into CRF01_AE transmission Clusters 1 (11.2%), 4 (64.5%), and 5 (7.2%). The CD4+ T-cell counts in Cluster 1, 4a, 4b are lower than 5 were 15, 38, 30, and 248 cells/mm3, respectively (P < 0.05). The high X4 tropism rates were 13.2%, 11.8%, 20.0%, and 0.0% in Clusters 1, 4a, 4b, and 5, respectively. DRM rates in Clusters 4a and 4b were 17.6%, and 25.45% respectively (P < 0.05), whereas they were 17.6% and 18.2% in Clusters 1 and 5, respectively. In total, 24 transmission genetic networks, comprising 72 sequences and 61 links, were discovered; of them, 61.2%, 11.7%, and 18.2% were from Clusters 4, 1, and 5, respectively (P < 0.05).Conclusion: In Zhejiang, different CRF01_AE clusters displayed unique clinic features. Cluster 4, particularly Cluster 4b, was considered a high-risk transmission cluster. The surveillance of epidemiology of HIV-1 should be enhanced to minimize its transmission.Keywords: HIV-1 CRF01_AE, drug resistance mutation, transmission cluster

Qian Meng,1,&ast; Xiaowei Yang,1,&ast; Zhongcheng Liu,2 Guoxing You,3 Wanyi Chen,3 Bing Zhao,1 Huizi Zhu,4 Liang Xu,1 Yan Zhou,1 Xiang Liu,1 Chunjuan Zhai,5 Rong Wang,1 Lian Zhao,3 Jing Sun1 1Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 2Department of Cardiovascular, The North City Hospital of Jinan, Jinan, Shandong, 250031, People’s Republic of China; 3Academy of Military Medical Sciences, Beijing, 100850, People’s Republic of China; 4Department of Nephrology, Fuyang People’s Hospital, Fuyang, Anhui, 236000, People’s Republic of China; 5Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Sun, Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, Shandong, 250021, People’s Republic of China, Tel +86 151 6888 6367, Email sunj5708@126.com Lian Zhao, Academy of Military Medical Sciences, 27 Taiping Road, Beijing, 100850, People’s Republic of China, Tel +8613671217095, Email zhaolian@bmi.ac.cnPurpose: Chronic kidney disease (CKD) is associated with persistent systemic inflammation. Reduced red blood cell (RBC) survival in patients with CKD has been identified for several decades. The purpose of this study is to explore whether excessive erythrophagocytosis exists and contributes to systemic inflammation in CKD.Patients and methods: A CKD rat model was induced by 5/6 nephrectomy. Erythrocyte osmotic fragility was determined with hypotonic NaCl solutions. Erythrocyte deformability was evaluated by filterability. RBC cell death was quantified using fluorescence-activated cell sorting analyses of fluorescent annexin V–bound surface phosphatidylserine (PS). Erythrophagocytosis was evaluated in vivo and in vitro. RT-qPCR and immunohistochemistry were used to determine the inflammatory effects after erythrophagocytosis.Results: Erythrocyte osmotic fragility and deformability progressively declined, and the percentage of PS-exposing RBCs progressively increased in CKD rats. Levels of erythrophagocytosis in vivo were evaluated by autologous injection of CFSE-labeled erythrocytes. In comparison with the control group, higher fluorescence intensity of CFSE was detected in the spleen homogenates of rats with CKD. In vitro, more of erythrocytes from 5/6Nx rats were phagocytosed by peritoneal macrophages in comparison to those from control rats. Compared with macrophages phagocytosed control erythrocytes, macrophages phagocytosed CKD erythrocytes exhibited higher mRNA levels of IL-6, CXCL-10, CXCL-11, iNOS, IL-1β, ICAM-1 and MCP-1. Compared with the control group, the red pulp of rats with CKD exhibited higher levels of p-NFκB, IL-6, iNOS and CXCL-10. ELISA results showed significantly increased plasma levels of both IL-6 and CXCL-10 in patients with long-term hemodialysis compared with those in healthy controls (2.30 ± 1.38 pg/mL vs 1.33 ± 0.65 pg/mL, P=0.01; 78.11 ± 27.34 pg/mL vs 37.45 ± 7.08 pg/mL, P=0.001).Conclusion: Our results indicated that excessive erythrophagocytosis may contribute to systemic inflammation in CKD. Keywords: chronic kidney disease, chronic inflammation, erythrocyte, phagocytosis

Ting Liu,1,* Chao Lei,1,* Qinhong Huang,2,* Weiqi Song,3 Chen Li,1 Ning Sun,4,5 Zhihua Liu6 1Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510799, People’s Republic of China; 2The First Clinical College, Guangzhou Medical University, Guangzhou, 511400, People’s Republic of China; 3Department of Public Health, Guangzhou Medical University, Guangzhou, People’s Republic of China; 4Guangzhou 11th People’s Hospital, Guangzhou Cadre and Talent Health Management Center, Guangzhou, 510530, People’s Republic of China; 5The State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, the Hong Kong Polytechnic University, 999077, Hong Kong, China; 6Department of Anorectal Surgery, the Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital), Dongguan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhihua Liu; Ning Sun, Email liuzhihua83@hotmail.com; ning.sun@connect.polyu.hkIntroduction: Obesity, which is associated with gut microbiota dysbiosis, low-grade chronic inflammation and intestinal barrier dysfunction, can cause a variety of chronic metabolic diseases. Phytochemical flavonoids have a variety of biological activities, among which there may be safe and effective anti-obesity solutions.Methods: We tested a plant-derived flavonoid hesperidin and fecal microbiota transplantation (FMT) to alleviate diet-induced obesity. High-fat diet (HFD)-fed mice were treated with hesperidin (100 and 200 mg/kg BW) and FMT.Results: Results indicated that hesperidin had the effects of reducing obesity as indicated by reduction of body weight, fat accumulation and blood lipids, reducing inflammation as indicated by reduction of pro-inflammation factors including TNFα, IL-6, IL-1βand iNOS, and improving gut integrity as indicated by increasing colon length, reducing plasma gut permeability indicators iFABP and LBP, increased mRNA expression of mucus protein Muc2, tight junction p Claudin 2, Occludin and ZO-1 in the HFD-fed mice. The anti-obesity effects of hesperidin treatment have a dose-dependent manner. In addition, 16S rRNA-based gut microbiota analysis revealed that hesperidin selectively promoted the growth of Lactobacillus salivarius, Staphylococcus sciuri and Desulfovibrio C21_c20 while inhibiting Bifidobacterium pseudolongum, Mucispirillum schaedleri, Helicobacter ganmani and Helicobacter hepaticus in the HFD-fed mice. Horizontal feces transfer from the normal diet (ND)-fed mice to the HFD-fed mice conferred anti-obesity effects and transmitted some of the HFD-modulated microbes.Conclusion: We concluded that hesperidin and FMT both affect the reduction of body weight and improve HFD-related disorders in the HFD-fed mice possibly through modulating the composition of the gut microbiota.Keywords: hesperidin, high-fat diet, obesity, gut microbiota, fecal microbiota transplantation

Abstract [Objective] PEX (pollen extensin-like) gene is involved in controlling pollen development, which plays a crucial role in embryogenesis of pollen microspores and haploid culture. In this study, the authors isolated the CaPEX3 gene from pepper and analyzed its protein structure and expression pattern, which provides a theoretical foundation for further investigation into the function of the CaPEX3 gene. [Methods] CaPEX3 was cloned by PCR, and its protein structure, evolution, and gene regulation were analyzed by bioinformatics. Expression of CaPEX3 in different tissues and pollen of different varieties were detected by qRT-PCR. Pollen viability of different pepper varieties was detected by staining method and their relationship with CaPEX3 expression was analyzed. [Results] The coding region of CaPEX3 was 1 581 bp in length, encoding 526 amino acids, which belongs to the LRX (leucine-rich repeats/extensins) gene family. The protein had phosphorylation and glycosylation sites, signaling peptides, and transmembrane domains. The expression level of CaPEX3 was the highest in flowers, and the gene expression was higher in tissues with high pollen vitality. The regulatory network predicted that CaPEX3 might be involved in the regulation of pollen development through the action of genes related to flower development. [Conclusion] CaPEX3 was specifically expressed in flowers, and a correlation was observed between its expression level and the activity of pollen grains. The analysis of gene expression and the construction of related vectors provided a theoretical foundation and technical support for the subsequent investigation of gene function and mechanism of CaPEX3

Abstract Inspired by the concept of “natural camouflage,” biomimetic drug delivery systems have emerged to address the limitations of traditional synthetic nanocarriers, such as poor targeting, susceptibility to identification and clearance, inadequate biocompatibility, low permeability, and systemic toxicity. Biomimetic nanocarriers retain the proteins, nucleic acids, and other components of the parent cells. They not only facilitate drug delivery but also serve as communication media to inhibit tumor cells. This paper delves into the communication mechanisms between various cell-derived biomimetic nanocarriers, tumor cells, and the tumor microenvironment, as well as their applications in drug delivery. In addition, the additional communication capabilities conferred on the modified biomimetic nanocarriers, such as targeting and environmental responsiveness, are outlined. Finally, we propose future development directions for biomimetic nanocarriers, hoping to inspire researchers in their design efforts and ultimately achieve clinical translation. Graphical Abstract

Kai-Wen Ho,1,2 Yen-Ling Liu,2,3 Tzu-Yi Liao,2,3 En-Shuo Liu,2,3 Tian-Lu Cheng1– 3 1Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanCorrespondence: Tian-Lu Cheng, Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, No. 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan, Tel +886 7 3121101 2697, Fax +886 7 3227508, Email tlcheng@kmu.edu.twAbstract: Polyethylene glycol (PEG)-modified nanoparticles (NPs) often struggle with reduced effectiveness against metastasis and liquid tumors due to limited tumor cell uptake and therapeutic efficacy. To address this, actively targeted liposomes with enhanced tumor selectivity and internalization are being developed to improve uptake and treatment outcomes. Using bi-functional proteins to functionalize PEGylated NPs and enhance targeted drug delivery through non-covalent attachment methods has emerged as a promising approach. Among these, the one-step and two-step targeting strategies stand out for their simplicity, efficiency, and versatility. The one-step strategy integrates streptavidin-tagged antibodies or bispecific antibodies (bsAbs: PEG/DIG × marker) directly into PEGylated NPs. This method uses the natural interactions between antibodies and PEG for stable, specific binding, allowing the modification of biotin/Fc-binding molecules like protein A, G, or anti-Fc peptide. Simply mixing bsAbs with PEGylated NPs improves tumor targeting and internalization. The two-step strategy involves first accumulating bsAbs (PEG/biotin × tumor marker) on the tumor cell surface, triggering an initial attack via antibody-dependent and complement-dependent cytotoxicity. These bsAbs then capture PEGylated NPs, initiating a second wave of internalization and cytotoxicity. Both strategies aim to enhance the targeting capabilities of PEGylated NPs by enabling specific recognition and binding to disease-specific markers or receptors. This review provides potential pathways for accelerating clinical translation in the development of targeted nanomedicine.Keywords: PEGylated nanoparticle, monoclonal antibody, antibody-containing nanodrugs, functionalization, targeted cancer therapy

Using multiple observations such as S-band radar (SPOL) in Shijiazhuang, X-band phased array radar (XPAR) in Xiong'an, and ground-based encrypted automatic stations, detection features and evolutions of EF2 tornado at Donglü Village, Qingyuan District of Baoding City Hebei Province on 21 July 2021 are studied. The tornado occurred within the center of high dew point values and in an area characterized by a significant temperature gradient. There are convergence lines within the center of high dew point temperatures and a temperature gradient zone. From perspectives of environmental conditions such as convective available potential energy (CAPE), 0-6 km vertical wind shear, and the lifting condensation level (LCL), there is a possibility for tornado occurrence. It is evident that the tornado formed within a low-vortex precipitation cloud system, showing significant divergence at high altitudes. The subsequent storm propagation leads to multiple single-cell mergers and a supercell formation. A significant reflectivity factor core moving from southeast to northwest is observed at the top of hook echo, corresponding to the tornado location. Both SPOL and XPAR detected continuous mesocyclones on average radial velocity images, with dimensions ranging from 1.4 to 4.2 km, and rotating speeds of 10-20 m·s-1, indicating weak mesocyclones with short durations (30-35 min). During tornado development, a decrease in the lower angle detection of adjacent rotational speed pairs coincides with mesocyclone downward extension to 1.2-1.4 km and its diameter shrinking to 0.8-1 km, indicating tornado formation. Tornado storm parameters show maximum rotation speed and vorticity at low levels, promoting its intensification. Compared with XPAR storm parameters, SPOL features a larger maximum reflectivity factor (noless than 55 dBZ) and a greater distribution height (8-10 km). The consistency of SPOL and XPAR in detecting the tornado location, radial velocity, and storm diameter is compared. On the radar radial velocity image, there are pairs of positive and negative velocity values arranged symmetrically along the radial direction. The echo top of XPAR radar is approximately 6 km higher than that of SPOL radar, and the peak time of XPAR echo coincides with the storm's appearance. The tornado vortex signature (TVS) reaches its strongest period from 1536 BT to 1542 BT, extending vertically up to 2-4 km.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disease caused by abnormal expression of glycosylphosphatidylinositol (GPI) on the cell membrane due to mutations in the phosphatidylinositol glycan class A(PIGA) gene. It is commonly characterized by intravascular hemolysis, repeated thrombosis, and bone marrow failure, as well as multiple systemic involvement symptoms such as renal dysfunction, pulmonary hypertension, swallowing difficulties, chest pain, abdominal pain, and erectile dysfunction. Due to the rarity of PNH and its strong heterogeneity in clinical manifestations, multidisciplinary collaboration is often required for diagnosis and treatment. Peking Union Medical College Hospital, relying on the rare disease diagnosis and treatment platform, has invited multidisciplinary clinical experts to form a unified opinion on the diagnosis and treatment of PNH, and formulated the Expert Consensus of Multidisciplinary Diagnosis and Treatment for Paroxysmal Nocturnal Hemoglobinuria (2024), with the hope of promoting the standardization of PNH diagnosis and treatment.

Objective To explore the clinical effectiveness of microparticle oral mucosa vaginoplasty.Methods A retrospective analysis was conducted on the clinical data of 149 patients with reproductive tract malformation (MRKH syndrome and vaginal atresia) who required vaginoplasty and were treated at Gansu Provincial Maternal and Child-Care Hospital from February 2013 to January 2024. Patients were divided into three groups based on the surgical method: oral mucosa vaginoplasty group (n=95), peritoneal vaginoplasty group(n=31), and biological patch vaginoplasty group (n=23). Surgical-related indicators, artificial vagina-related indicators, and sexual function indicators were compared to evaluate the clinical effectiveness of microparticle oral mucosa vaginoplasty. Results The oral mucosa group and the biological patch group demonstrated significantly better outcomes in terms of operation time and blood loss compared to the peritoneal group(P

Jiyang shale oil resources have enormous potential. However， there is a lack of systematic understanding of seepage mechanism and development laws in the multi-scale spaces after fracturing due to the influence of complex geological conditions， making it difficult to achieve large-scale beneficial development. In order to clarify the formation mechanism of the development law of Jiyang shale oil， the multi-scale fracture characteristics of Jiyang shale oil were analyzed. The formation mechanism and combination mode of fracture networks after fracturing were studied using physical experiments and numerical simulations. In addition， seepage mechanisms in multi-medium spaces were researched， including the stress sensitivity of multi-scale fractures， nonlinear flow in multi-scale pores and fractures， and imbibition displacement of pore-fracture systems. According to the differences in the distribution of multi-scale fracture networks and their flow laws after fracturing， a three-zone flow pattern of “easy flow-slow flow-difficult flow” for shale oil was established. Finally， the flow characteristics and production laws of Jiyang shale oil at different flow stages were clarified. The research results indicated that the developed bedding fractures could improve the physical properties of reservoirs， enhance imbibition displacement efficiency， and reduce start-up pressure gradient. During the elastic development stage， the flow channels reduce， and the fracture network conductivity decreases as the formation pressure declines， resulting in significant stress sensitivity. In the development process of Jiyang shale oil， the initial flow state is mainly dominated by linear flow and elliptical flow of fractures supplied by the easy flow zone. In the middle stage of development， the slow flow zone supplies energy to the easy flow zone， and the flow state changes to elliptical flow in the formation. Moreover， the shale oil in the difficult flow zone is gradually produced， and the flow state changes to boundary-controlled flow in the later stage of development. Due to the influence of geological conditions and production systems， there are significant differences in the energy change， water cut decrease， and production change law of different horizontal wells. Reasonably optimizing the shut-in time and production system can ensure imbibition displacement efficiency， efficiently utilize formation energy， and improve shale oil production capacity.

In order to realize the effective development of shale oil with low maturity in continental faulted basins in Jiyang Depression， systematic evaluations have been carried out simultaneously in Boxing， Niuzhuang， and Minfeng sags since 2019， based on the 10 000 meters of systematic coring and more than 100 000 core tests. Significant breakthroughs have been made in single well evaluation and stereoscopic development of well groups. A pilot test of eight wells in three layers was conducted in Boxing Sag， and the first 100 000-ton shale oil development well group of SINOPEC was built. A large-platform stereoscopic development test of well groups was carried out with 20 wells in five layers， and all wells were put into production in Niuzhuang Sag. A comprehensive overall evaluation and stereoscopic development test was launched in Minfeng Sag， following the mode of “overall deployment of a large platform and step-by-step implementation of a small well group.” Peak daily oil production exceeded one hundred tons in 28 wells， including Wells FYP1 and FY1-1HF ternary-element （storage， fracture， and pressure） storage and flow theory of shale oil in Jiyang Depression was proposed. The technologies of shale oil development， stereoscopic fine evaluation of development sweet spots， integrated modeling and numerical simulation， and stereoscopic development optimization were developed. A theoretical and technical system of stereoscopic development of shale oil in continental faulted basins with Shengli characteristics was initially constructed. It effectively supported the construction of the shale oil national demonstration area in Jiyang Depression， Shengli Oilfield.

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

Ticks are obligate blood-feeding arthropods that cause significant economic losses in domestic animal husbandry and threaten public health. However, information about soft ticks (Acari: Argasidae) and tick-borne pathogens in the Xinjiang Uygur Autonomous Region (XUAR) of China is scarce.

Jing Ye,1,2,&ast; Ping Li,1,2,&ast; Pengcheng Liu,1,2 Wenjing Pei,1,2 Ruowen Wang,1,2 Hui Liu,1,2 Changxiu Ma,1,2 Dahai Zhao1,2 1Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of China; 2Institute of Respiratory Diseases, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dahai Zhao, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Anhui Medical University, 678 Furong Road, Hefei, Anhui Province, 230601, People’s Republic of China, Email zhaodahai@ahmu.edu.cnBackground: Anxiety and depression are two of the most common comorbidities of COPD, which can directly lead to the number of acute exacerbations and hospitalizations of COPD patients and reduce their quality of life. At present, there are many studies on anxiety and depression in stable COPD, but few studies on anxiety and depression in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients.Objective: We aim to explore the changes of serum metabolomics in AECOPD complicated with anxiety and depression and to provide some clues for further understanding its pathogenesis.Methods: This is an observational high-throughput experimental study based on retrospective data extraction. Twenty-one AECOPD with anxiety and depressive patients and 17 healthy controls (HCs) were retrospectively enrolled in the Second Affiliated Hospital of Anhui Medical University. Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) for anxiety and depression were used to assess the patients with AECOPD. Untargeted metabolomics analysis was carried out to investigate different molecules in the serum of all participants. General information of all participants, baseline data and clinical measurement data of AECOPD patients were collected. Statistical analysis and bioinformatics analysis were performed to reveal different metabolites and perturbed metabolic pathways.Results: A total of 724 metabolites in positive ionization mode and 555 metabolites in negative ionization mode were different in AECOPD patients with anxiety and depression. The 1,279 serum metabolites could be divided into 77 categories. Based on multivariate and univariate analysis, 74 metabolites were detected in positive ionization mode, and 60 metabolites were detected in negative ionization as differential metabolites. The 134 metabolites were enriched in 18 pathways, including biosynthesis of unsaturated fatty acids, aldosterone synthesis and secretion, protein digestion and absorption, ovarian steroidogenesis, long−term depression, retrograde endocannabinoid signaling, and so on.Conclusion: This work highlights the key metabolites and metabolic pathways disturbed in AECOPD patients with anxiety and depression. These findings support the use of metabolomics to understand the pathogenic mechanisms involved in AECOPD patients with anxiety and depression.Keywords: metabolomics, AECOPD, anxiety, depression, exacerbation

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

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

Yuetong Liu,1,&ast; Lanxin Liu,1,&ast; Hongmei Zhou,2 Guangfang Chen,2 Changhui Wen,2 Ran Wu2 1Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, 550002, People’s Republic of China; 2Department of Dermatology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, 550001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ran Wu, Department of Dermatology, The first affiliated hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, 550001, People’s Republic of China, Email wuranshou@126.comAbstract: Atopic dermatitis (AD) and psoriasis (Pso) are both recurrent inflammatory diseases. Recently, it has been reported that a small number of AD patients experience immune drift after receiving dupilumab treatment, leading to a transition from eczema-like lesions to psoriasis-like lesions. Here, we report a case of pustular psoriasis caused by dupilumab treatment for atopic dermatitis. This case underscores the diagnostic challenges associated with immune drift related to biological agents while also highlighting the shortened time frame for immune drift onset compared to previous reports.Keywords: immune drift, dupilumab, atopic dermatitis, pustular psoriasis

Zixu Zhang,1,2 Muhan Chen,1,2 Jiahua Wang,1,2 Mo Liu,1,2 Ruibo Guo,1,2 Lu Zhang,1,2 Liang Kong,1,2 Yang Liu,1,2 Yang Yu,1– 3 Xuetao Li1,2 1School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, People’s Republic of China; 2Shenyang Key Laboratory of Chinese Medicine targeted Delivery Key laboratory, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People’s Republic of China; 3Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, 110032, People’s Republic of ChinaCorrespondence: Xuetao Li; Yang Yu, School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, People’s Republic of China, Tel +86411 8589 0170, Fax +86411 8589 0128, Email lixuetao1979@163.com; yuqn0702@163.comIntroduction: Resistance of intracellular pathogens is a challenge in microbial therapy. Methicillin-resistant Staphylococcus aureus (MRSA), which is able to persist inside the cells of infected tissues, is protected from attack by the immune system and many antimicrobial agents. To overcome these limitations, nano-delivery systems can be used for targeted therapy of intracellular MRSA.Methods: Hyaluronic acid-modified azithromycin/quercetin micelles (HA-AZI/Qe-M) were synthesized by thin film hydration. The micelles were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and Fourier transform infrared spectroscopy (FTIR), and the drug loading (DL) and encapsulation efficiency (EE) were detected by high performance liquid chromatography (HPLC). The uptake ability of RAW264.7 cells was investigated, and its distribution in mice was evaluated by in vivo imaging. The inhibitory effect of the micelles against MRSA in vitro and its ability to eliminate intracellular bacteria were evaluated. Bacterial muscle-infected mice were constructed to evaluate the therapeutic effect of the micelles on bacterial infections in vivo and the biocompatibility of the micelles was investigated.Results: HA-AZI/Qe-M had suitable physical and chemical properties and characterization. In vitro antibacterial experiments showed that HA-AZI/Qe-M could effectively inhibit the growth of MRSA, inhibit and eliminate the biofilm formed by MRSA, and have an excellent therapeutic effect on intracellular bacterial infection. The results of RAW264.7 cells uptake and in vivo imaging showed that HA-AZI/Qe-M could increase the cellular uptake, target the infection site, and prolong the treatment time. The results of in vivo antibacterial infection experiments showed that HA-AZI/Qe-M was able to ameliorate the extent of thigh muscle infections in mice and reduce the expression of inflammatory factors.Conclusion: HA-AZI/Qe-M is a novel and effective nano-drug delivery system that can target intracellular bacterial infection, and it is expected to be safely used for the treatment of MRSA infection.Keywords: MRSA, hyaluronic acid, antibiotics, micelles, azithromycin, quercetin

Abstract Introduction In the current study, we screened for highly sensitive and specific predictors of premature birth, with the aim to establish an sPTB prediction model that is suitable for women in China and easy to operate and popularize, as well as to establish a sPTB prediction scoring system for early, intuitive, and effective assessment of premature birth risk. Methods A total of 685 pregnant women with a single pregnancy during the second trimester (16–26 weeks) were divided into premature and non-premature delivery groups based on their delivery outcomes. Clinical and ultrasound information were collected for both groups, and risk factors that could lead to sPTB in pregnant women were screened and analyzed using a cut-off value. A nomogram was developed to establish a prediction model and scoring system for sPTB. In addition, 119 pregnant women who met the inclusion criteria for the modeling cohort were included in the external validation of the model. The accuracy and consistency of the model were evaluated using the area under the receiver operating characteristic (ROC) and C-calibration curves. Results Multivariate logistic regression analysis showed a significant correlation (P

Cheng-Jie Mao,1,&ast; Hao Peng,2,&ast; Sheng Zhuang,1,&ast; Ying-Chun Zhang,3 Wei-Ye Xie,1 Jia-Hui Yan,1 Hui-Hui Liu,1 Jing Chen,1 Jun-Yi Liu,4 Jianan Zhang,5 Hai Jiang,5 Yonghong Zhang,2 Mingzhi Zhang,2 Chun-Feng Liu1,6 1Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Epidemiology, School of Public Health, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 3Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 4Department of Neurology, The Fourth Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 5Department of Chronic Disease, Taicang Center of Disease Prevention and Control, Suzhou, People’s Republic of China; 6Institute of Neuroscience, Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun-Feng Liu, Department of Neurology and Clinical Research Center of Neurological Disease, the Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, People’s Republic of China, Email liuchunfeng@suda.edu.cn Mingzhi Zhang, Department of Epidemiology, School of Public Health, Medical College of Soochow University, 199 Renai Road, Industrial Park, Suzhou, 215123, People’s Republic of China, Email zhangmingzhi@suda.edu.cnBackground: Sleep is critical in health problems including Parkinson’s disease (PD). This study examined the association between sleep characteristics and the likelihood of prodromal PD.Methods: At baseline examination of the Heart and Brain Investigation in Taicang (HABIT) study, potential PD biomarkers were obtained for 8777 participants aged over 50 years, and the probability of prodromal PD was assessed based on the Chinese expert consensus and Movement Disorder Society (MDS) criteria. General and component sleep characteristics were evaluated by the Pittsburgh Sleep Quality Index (PSQI). Median regression was applied to examine the association between sleep and the probability of prodromal PD, adjusting for age, sex, education level, physical activity, obesity, fast plasma glucose, lipids, and hypertension.Results: Based on China criteria, a higher level of PSQI score was significantly associated with a higher probability of prodromal PD (β = 0.02, 95% CI: 0.01– 0.03) and a higher risk of having an increased probability of prodromal PD (OR = 1.04, 95% CI: 1.02– 1.05). Compared to participants with good quality sleep, those with poor quality sleep had a 0.07% increased probability of prodromal PD (95% CI: 0.01– 0.13) and a 19% increased risk of having a high prodromal PD probability (95% CI: 1.04– 1.20). Similar associations between sleep quality and the probability of prodromal PD were also observed using the MDS criteria. Subjective sleep quality, sleep latency, habitual sleep efficiency, daytime dysfunction, and use of sleep medications were also associated with the probability of prodromal PD.Conclusion: Poor sleep quality was associated with a high probability of prodromal PD. Sleep may be helpful for understanding and intervention of prodromal PD.Keywords: prodromal Parkinson’s disease, sleep, Parkinson’s disease

Ruixi Li,1 Lulu Liu,1 Yong Liu,1 Jiang Tang,1 Jinsong Li2 1Yueyang Guangji Hospital, Yueyang, Hunan, People’s Republic of China; 2Department of Spine Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Jinsong Li, Department of Spine Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China, Tel +86-731-88618826, Fax +86-731-88618526, Email jinsongli_csu@163.comIntroduction: Protocadherin 9 (PCDH9), a member of the cadherin superfamily of transmembrane proteins, plays a role in cell adhesion and neural development. Recent studies suggest that PCDH9 may function as a tumor suppressor in certain cancers, though its specific role in breast cancer remains unclear.Methods: UALCAN database to retrieve information on PCDH9 expression in breast cancer tissues compared with that in normal tissues. The biological effects of PCDH9 in breast cancer cells were analyzed using the DepMap database. Stable knockdown or overexpression of PCDH9 in breast cancer cell lines and subsequently assessed tumor cell proliferation and migration. Synthetic lethal screening was conducted for breast cancer cells with low PCDH9 expression or deficiency.Results: In this study, we observed significant downregulation of PCDH9 in breast cancer tissues, with its expression negatively correlated with progression-free survival. Further investigations revealed that decreased PCDH9 expression promotes breast cancer cell proliferation and migration, while overexpression of PCDH9 has the opposite effect. Subsequently, we identified the TAS-102, an approved drug for metastatic colorectal cancer, exhibited selective cytotoxicity against breast cancer cells with low PCDH9 expression.Conclusion and discussion: In summary, our study identified PCDH9 as a tumor suppressor in breast cancer and highlighted TAS-102 as a potential therapeutic option for tumors with low PCDH9 expression or deficiency. The specific interaction between TAS-102 and PCDH9 warrants further exploration, providing deeper insights into its mode of action in treating PCDH9-deficient breast cancer.Keywords: breast cancer, PCDH9, synthetic lethality, TAS-102

Qingqing Shen,1– 3,&ast; Qing Zhang,2,3,&ast; Yunxiao Liu,1– 3,&ast; Yingao Cui,1– 3 Jingwen Shang,1– 3 Xiaoping Yuan,2,3 Feng Geng,4 Liang Sun,5 Zhiwei Liu,5 Rongchun Yang,5 Kai Zhang,2,3 Huanzhong Liu2,3,6 1Department of Psychiatry, School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Anhui Psychiatric Center, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 4Department of Psychology and Sleep Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 5Department of Psychiatry, Fuyang Third People’s Hospital, Fuyang, Anhui, People’s Republic of China; 6Brain Bank Construction and Resource Utilization, Anhui Provincial Key Laboratory, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Zhang; Huanzhong Liu, Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China, Email zhangkai@ahmu.edu.cn; huanzhongliu@ahmu.edu.cnPurpose: The purpose of this study was to further explore the association of pain intensity and sensitivity with suicidal ideation in adolescents with depressive disorder by comparing the differences in pain intensity and sensitivity between adolescent patients with depressive disorders and healthy controls.Patients and Methods: A consecutive enrollment method was used to select 158 adolescent patients with depressive disorders from three hospitals in Anhui Province as the MDD group, and 47 healthy adolescents were recruited as the Control group. The subjects’ suicidal ideation was assessed using the Positive and Negative Suicide Ideation scale (PANSI), and the intensity of somatic pain was assessed using the Numerical Rating Scale-11 (NRS-11). Subjects were assessed for forearm and tibial pain sensitivity using a hand-held pressure pain instrument, and experimental pain sensitivity measures included pressure pain threshold (PPT) and pressure pain tolerance (PTO). Differences in pain intensity and sensitivity between the MDD group and the Control group were compared, and the association of pain intensity and sensitivity with suicidal ideation was analyzed.Results: The incidence of physical pain in adolescent depressive disorder was higher at 88.6%, which was significantly higher than the Control group (P< 0.001), and the pain intensity in the MDD group (3.77± 2.48) was significantly higher than the Control group (0.617± 0.99) (P < 0.001).The Pain tolerance was significantly higher in the MDD group (forearm 105.37 ± 41.46; tibia 121.29 ± 41.60) than in the Control group (forearm 91.92 ± 37.62; tibia 105.47 ± 35.52) (P < 0.05).Linear regression analysis showed that the greater the pain intensity and pain tolerance, the higher the total PANSI score.Binary logistic regression showed that pain intensity was an influencing factor for suicidal ideation.Conclusion: Adolescents with depressive disorders have higher pain intensity and lower pain sensitivity than healthy adolescents. Increased pain intensity and pain tolerance were positively correlated with suicidal ideation.Keywords: adolescents, depressive disorder, pain intensity, pain sensitivity, suicidal ideation