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Rui Shi,1,* Wenbo Xu,1 Lei Feng,2,* Dan Ye,1 Beibei Luo,1 Yanmei Liu,2,3 Huiying Cao,1 Lingtong Tang1 1Department of Laboratory, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi City, Yunnan Province, People’s Republic of China; 2Clinical Laboratory, Yan’an Hospital of Kunming City, Kunming City, Yunnan Province, People’s Republic of China; 3Department of Laboratory Medicine, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenbo Xu, Department of Laboratory, The Sixth Affiliated Hospital of Kunming, Medical University, Yuxi City, Yunnan Province, People’s Republic of China, Tel +86 877 2014128, Email xwb103196@sina.com Lei Feng, Clinical Laboratory, Yan’an Hospital of Kunming City, Kunming City, Yunnan Province, People’s Republic of China, Tel +86 871 63612494, Email fngj2004@163.comAim: This investigation aims to assess the predictive value of the glycemic dispersion index (GDI), calculated by incorporating glycated hemoglobin, fasting plasma glucose, and 2-hour postprandial plasma glucose, in predicting major adverse cardiovascular events (MACE) within a 12-month timeframe for diabetic patients with concomitant acute coronary syndrome (ACS).Methods: A retrospective study was conducted on 3261 diabetic patients with ACS who were hospitalized in the Department of Cardiology, the Sixth Affiliated Hospital of Kunming Medical University, from January 2016 to July 2022. Based on the inclusion and exclusion criteria, 512 patients were ultimately enrolled in the study. Their general information and laboratory test indicators were collected, and the occurrence of MACE within 12 months after admission was followed up and recorded for the enrolled patients, With the last follow-up having been concluded on July 31, 2023. The enrolled patients were stratified into four groups (Q1, Q2, Q3, Q4) based on their GDI values, from the lowest to the highest. Cox proportional hazards regression analysis and Kaplan-Meier survival analysis were employed to investigate the risk factors associated with MACE occurrence across these groups and to assess the cumulative risk of MACE over time within each group.Results: The percentages of enrolled patients experiencing MACE in groups Q1 to Q4 were 10.16%, 12.50%, 15.63%, and 16.41%, respectively. GDI independently predicted the hazards for MACE in enrolled patients. The cumulative risk of MACE over time was considerably more significant in those with a GDI> 4.21 than those with a GDI≤ 4.21.Conclusion: The elevated GDI is correlated with an augmented risk of MACE in diabetic patients with concomitant ACS, thereby serving as an early indicator for assessing the unfavorable clinical prognosis of patients. This study offers novel insights into glycemic variability monitoring, enhancing prevention and treatment strategies for cardiovascular disease in people with diabetes.Keywords: diabetes, acute coronary syndrome, major adverse cardiovascular events, glycemic dispersion index, glycemic variability

Xiaowu Wang,1,2 Tuantuan Li,1,2 Yan Liu,1,2 Yilang Zhu,1,2 Lichang Chen,1,2 Yong Gao1,2 1Department of Clinical Laboratory, The Second People’s Hospital of Fuyang City, Fuyang, Anhui, People’s Republic of China; 2Department of Clinical Laboratory, Fuyang Infection Disease Clinical College of Anhui Medical University, Fuyang, Anhui, People’s Republic of ChinaCorrespondence: Yong Gao, The Second People’s Hospital of Fuyang City, No. 1088, West Yinghe Road, Fuyang, Anhui, People’s Republic of China, Email fyeryuangy8@126.comObjective: We retrospectively review consecutive patients with nontuberculous mycobacterium (NTM) pulmonary disease reported from a designated hospital for infectious diseases in the Fuyang district of China to determine the clinical characteristics of these patients.Methods: This research enrolled 234 patients with NTM pulmonary disease between January 2018 and May 2023 in the Fuyang district of China. Data were collected from the electronic medical records. The NTM strain composition and clinical characteristics of NTM pulmonary disease were retrospectively analyzed.Results: 73 (31.20%) patients had previous tuberculosis (TB) or TB exposure history and bronchiectasis. Mixed NTM infection accounted for 12.39%. Mycobacterium intracellulare strain was detected in 132 patients (49.62%). Women were found to be more affected by Mycobacterium avium infection, and men by Mycobacterium abscessus infection. Mycobacterium avium (34.21%) and Mycobacterium abscessus (33.33%) strains were most common in people with previous TB or TB exposure history. Among respiratory tract-related diseases, patients with bronchiectasis had the highest isolation rate of Mycobacterium avium (55.36%). Women were susceptible to bronchiectasis (P < 0.01). The median of mononuclear-to-lymphocyte ratio (MLR) was higher in men than in women (P < 0.01). The serum albumin (ALB) level was lower in patients with TB or TB exposure history than in those without TB history (P = 0.034). The prognostic nutritional index (PNI) was lower in patients with TB or TB exposure history than in those without tuberculosis history (P = 0.021). Patients with NTM lung disease were poorly treated.Conclusion: Clinical symptoms of the disease were not species-specific. Mycobacterium intracellulare and Mycobacterium avium strains were predominant in the Fuyang district of China. Previous TB or TB exposure history immensely enhanced the risk of NTM disease.Keywords: NTM, clinical symptoms, tuberculosis exposure history, bronchiectasis

Jing Sun,1 Tracy Lu,1 Yan Dang,1 Zigang Xu,2 Ying Liu2 1Medical & Scientific Affairs, Haleon (Formerly GSK Consumer Healthcare), Shanghai, People’s Republic of China; 2Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Key Discipline of Pediatrics, Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children‘s Health, Beijing, People’s Republic of ChinaCorrespondence: Ying Liu, Department of Dermatology, Beijing Children’s Hospital, Capital Medical University, National Key Discipline of Pediatrics, Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children’s Health, Beijing, People’s Republic of China, Email ying_lemon@aliyun.comAbstract: Mupirocin, an antibiotic produced by Pseudomonas fluorescens, is mainly used for the topical treatment of various skin and soft tissue infections caused by Staphylococcus (including methicillin-resistant Staphylococcus aureus) and Streptococcus around the world for decades. Nevertheless, the clinical application scope of mupirocin varies in different countries due to differences in their medical policies, prescription types, and drug resistance. According to the experience of Chinese doctors in the past few years, mupirocin presented low drug resistance rates, and could be used as a treatment option for various primary infections and secondary infections, with antibacterial effects in a broad application. In this review, we summarized the experience of mupirocin used in the Chinese population and discussed its clinical value to provide novel insights and inspiration for physicians.Keywords: experience, mupirocin, skin diseases, infectious

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

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

Mengfan Yang,1,&ast; Youqun Huang,1,&ast; Anqi Tang,1 Yu Zhang,2 Yu Liu,3 Zhenliang Fan,4 Mingquan Li1 1Department of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Nephrology, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi’an, Shaanxi Provincial, People’s Republic of China; 3Department of Nephrology, South China Hospital, Health Science Center, Shenzhen University, Shenzhen, People’s Republic of China; 4Department of Nephrology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingquan Li, Department of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China, Email limingquan@cdutcm.edu.cnPurpose: Acute kidney injury (AKI) is a common clinical critical condition that has become a significant healthcare burden. In recent years, the relationship between AKI and mitochondria has attracted increasing attention. Protecting mitochondria or restoring their function has emerged as a novel therapeutic strategy for alleviating AKI. This study aims to analyze and summarize the current status, research trends, and hotspots in this field, providing references and directions for future research.Methods: AKI and mitochondria-related literature from the Web of Science core collection were retrieved and collected. Bibliometric and visualization analyses were conducted using Microsoft Excel 2021, bibliometric tools (VosViewer, Citespace 6.3.R1, and the bibliometrix R package), R 4.3.2, and SCImagoGraphica software.Results: A total of 2433 publications were included in this study. The number of annual publications in this field has increased year by year. China and the United States are the two most productive countries. Central South University is the most influential research institution in terms of research output, and Parikh SM, Schnellmann RG, and Dong Z are the most influential authors in this field. KIDNEY INTERNATIONAL, JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, and AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY are the most influential journals. Initially, the research focused on keywords such as oxidative stress, ischemia-reperfusion injury, apoptosis, inflammation, and autophagy. In recent years, new research hotspots have emerged, including ferroptosis, aging, mitochondrial quality control, messenger RNA, mitochondrial-targeted antioxidants, extracellular vesicles, and nanodrug delivery.Conclusion: Research on the relationship between mitochondria and AKI has broad developing prospects, and targeting mitochondrial regulation will become a focus of future AKI prevention and treatment research.Keywords: acute kidney injury, mitochondria, bibliometric analysis, visualization, VOSviewer, citespace

Tianjie Zhang,1 Yan Liu,1 Dongwei Xu,2 Rui Dong,1 Ye Song1 1Department of Ultrasonography, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318, People’s Republic of China; 2Department of Critical Care Medicine, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Ye Song, Email songye@tongji.edu.cnBackground: In recent years, diaphragm ultrasound (DUS) has been used to identify diaphragm dysfunction in the intensive care unit (ICU). However, there are few studies on DUS parameters to evaluate function, normal ranges, and influencing factors in population. The aim of this study is to provide a methodological reference for clinical evaluation of diaphragm function by measuring different DUS parameters in a healthy population.Methods: A descriptive study was conducted 212 (105 males, 107 females) subjects with normal spirometry underwent ultrasound imaging in this study. The diaphragm contraction and motion related parameters and shear wave velocity (SWV) were measured in the supine position. The effects of gender, age, body mass index (BMI) and lifestyle on diaphragm ultrasound parameters were analyzed.Results: The diaphragm thickness at end-expiration (DT-exp) was 0.14 ± 0.05 cm, the diaphragm thickness at end- inspiration (DT-insp) was 0.29± 0.10 cm, with thickening fraction (TF) was 1.11± 0.54. The diaphragm excursion (DE) was 1.68± 0.37cm and diaphragm velocity was 1.45± 0.41 cm/s during calm breathing. During deep breathing, the DE was 5.06± 1.40cm and diaphragm velocity was 3.20± 1.18 cm/s. The Diaphragm shear modulus—longitudinal view were Mean16.72± 4.07kPa, Max25.04± 5.58kPa, Min11.06± 3.88kPa, SD2.56± 0.98. The results of diaphragmatic measurement showed that the DT of males was significantly greater than that of females (P< 0.05), but there was no significant difference in TF. The DT-insp (r=0.155, P= 0.024) and the DT-exp (r=0.252, P=0.000) were positively correlated with age, and the DE during calm breathing was negatively correlated with age (r=− 0.218, P= 0.001) and BMI (r=− 00.280, P= 0.000). The DE (R=0.371, P=0.000) and velocity (R=0.368, P=0.000) during deep breathing were correlated with lifestyle.Conclusion: Our study provides normal reference values of the diaphragm and evaluates the influence of gender, age, body mass index and lifestyle on diaphragmatic morphology.Keywords: diaphragm, reference values, ultrasound, supine position

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

Zhuohua Zhang,1,2 Yan Liu,2 Da Huang,2 Zhaohe Huang1,3,4 1Department of Cardiology, First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 2Department of Cardiology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, People’s Republic of China; 3Affiliated Southwest Hospital, Youjiang Medical University for Nationalities, Baise, 533000, People’s Republic of China; 4Graduate School, Youjiang Medical University for Nationalities, Baise, 533000, People’s Republic of ChinaCorrespondence: Zhaohe Huang, Department of Cardiology, First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China, Tel +86 13977691455, Fax +86 776-2853272, Email bshuangzhaohe@163.comPurpose: Myocardial ischemia-reperfusion injury (MIRI) is characterized by inflammation and ferroptosis, but the precise mechanisms remain unknown. This study used single-cell transcriptomics technology to investigate the changes in various cell subtypes during MIRI and the regulatory network of ferroptosis-related genes and immune infiltration.Methods: Datasets GSE146285, GSE83472, GSE61592, and GSE160516 were obtained from Gene Expression Omnibus. Each cell subtype in the tissue samples was documented. The Seurat package was used for data preprocessing, standardization, and clustering. Cellphonedb was used to investigate the ligand-receptor interactions between cells. The hdWGCNA analysis was used to create a gene co-expression network. GSVA and GSEA were combined to perform functional enrichment and pathway analysis on the gene set. Furthermore, characteristic genes of the disease were identified using Lasso regression and SVM algorithms. Immune cell infiltration analysis was also performed. MIRI rat models were created, and samples were taken for RT-qPCR and Western blot validation.Results: The proportion of MIRI samples in the C2, C6, and C11 subtypes was significantly higher than that of control samples. Three genes associated with ferroptosis (CD44, Cfl1, and Zfp36) were identified as MIRI core genes. The expression of these core genes was significantly correlated with mast cells and monocyte immune infiltrating cells. The experimental validation confirmed the upregulation of Cd44 and Zfp36 expression levels in MIRI, consistent with current study trends.Conclusion: This study used single-cell transcriptomics technology to investigate the molecular mechanisms underpinning MIRI. Numerous important cell subtypes, gene regulatory networks, and disease-associated immune infiltration were also discovered. These findings provide new information and potential therapeutic targets for MIRI diagnosis and treatment.Keywords: myocardial ischemia-reperfusion injury, ferroptosis, immune cell infiltration, single-cell transcriptome sequencing, WGCNA

Chunjiao Lu,&ast; Xuewei Wu,&ast; Xin Meng,&ast; Yi Liu, Ting Yang, Yan Zeng, Yang Chen, Yishan Huang, Zhou Fang, Xiaojun Yang, Juanjuan Luo Engineering Research Center of Key Technique for Biotherapy of Guangdong Province, Shantou University Medical College, Shantou, 515041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaojun Yang; Juanjuan Luo, Shantou University Medical College, 22 Xinling Road, Shantou, 515041, People’s Republic of China, Email yangx@stu.edu.cn; 15jjluo1@stu.edu.cnIntroduction: The potential toxic effects of wastewater discharges containing silver nanoparticles (AgNPs) and their release into aquatic ecosystems on aquatic organisms are becoming a major concern for environmental and human health. However, the potential risks of AgNPs to aquatic organisms, especially for cardiac development by Focal adhesion pathway, are still poorly understood.Methods: The cardiac development of various concentrations of AgNPs in zebrafish were examined using stereoscopic microscope. The expression levels of cardiac development-related genes were analyzed by qRT-PCR and Whole-mount in situ hybridization (WISH). In addition, Illumina high-throughput global transcriptome analysis was performed to explore the potential signaling pathway involved in the treatment of zebrafish embryos by AgNPs after 72 h.Results: We systematically investigated the cardiac developing toxicity of AgNPs on the embryos of zebrafish. The results demonstrated that 2 or 4 mg/L AgNPs exposure induces cardiac developmental malformations, such as the appearance of pericardial edema phenotype. In addition, after 72 h of exposure, the mRNA levels of cardiac development-related genes, such as myh7, myh6, tpm1, nppa, tbx5, tbx20, myl7 and cmlc1, were significantly lower in AgNPs-treated zebrafish embryos than in control zebrafish embryos. Moreover, RNA sequencing, KEGG (Kyoto Encyclopedia of Genes) and Genomes and GSEA (gene set enrichment analysis) of the DEGs (differentially expressed genes) between the AgNPs-exposed and control groups indicated that the downregulated DEGs were mainly enriched in focal adhesion pathways. Further investigations demonstrated that the mRNA levels of focal adhesion pathway-related genes, such as igf1ra, shc3, grb2b, ptk2aa, akt1, itga4, parvaa, akt3b and vcla, were significantly decreased after AgNPs treatment in zebrafish.Conclusion: Thus, our findings illustrated that AgNPs could impair cardiac development by regulating the focal adhesion pathway in zebrafish.Keywords: AgNPs, focal adhesion, cardiac development, zebrafish

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

Kai Hong,1,&ast; Yan Liu,1,&ast; Hao Yin,2 Ke Huang,2 Xiao-Li Pu,1 Zhuan-Xu Zhu1 1Department of Gynaecology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China; 2Department of Obstetrics, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuan-Xu Zhu, Email 13636196733@163.comBackground: Ovarian cancer (OC) remains the deadliest gynecologic malignancy worldwide due to delayed diagnosis, recurrence, and drug resistance. This study aimed to identify key factors affecting delayed diagnosis in OC patients.Methods: A retrospective analysis was conducted on OC patients treated at Taihe Hospital, Hubei University of Medicine from June 2023 to September 2023. Patients were categorized based on a three-months cut-off point for delayed diagnosis. Collected data included demographics, tumor incidence, and disease cognition. The analysis of variance and the chi-squared test was used for comparison between groups.Results: The significant differences were found in age, residence, education level, family income, family history of tumor, histology, FIGO stage, and tumor location between groups (P< 0.05). Multifactorial logistic regression analysis identified education level [odds ratio (OR) = 0.606; 95% confidence interval (CI): 0.440, 0.833; P = 0.002], family history of tumor (OR = 0.462; 95% CI: 0.214, 0.997; P = 0.049), emotional barriers (OR = 1.332; 95% CI: 1.081, 1.642; P = 0.007), and practical barriers (OR = 2.964; 95% CI: 2.195, 4.004; P < 0.001) as risk factors for delayed diagnosis of OC.Conclusion: Patient cognition is crucial in OC diagnosis delay. Enhancing public awareness and understanding of OC is essential to eliminate fear and improve early diagnosis.Keywords: ovarian cancer, delayed diagnosis, disease awareness, emotional barriers

Fan Yang,1,&ast; Limin Pan,2,&ast; Xiaoyun Zhang,1,&ast; Jiaan Huang,3 Yan Liu,3 Peixuan Li,3 Yuehua Wang1,3,4 1College of Integrated Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050091, People’s Republic of China; 2First Affiliated Hospital, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050033, People’s Republic of China; 3College of Integrated Chinese and Western Medicine, Hebei University of Chinese Medicine, Hebei University of Chinese Medicine & Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang, Hebei, 050091, People’s Republic of China; 4Second Affiliated Hospital, Hebei University of Chinese Medicine, Hebei, 073000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuehua Wang, Email wangyuehua@hebcm.edu.cnPurpose: Preventing and treating diabetic nephropathy (DN) are global challenges due to the complexity and diversity of its causes and manifestations. It is important to find effective medications to treat DN.Patients and Methods: Gene expression files of DN were downloaded from the GEO database to identify the differentially expressed genes. Network pharmacology and molecular docking were used to explore the possible mechanisms of modified Buyang Huanwu Decoction (mBHD) in treating DN. Biochemical, histopathological, and real-time PCR analyses were conducted in both in vivo and in vitro DN models to investigate the effects of mBHD.Results: A total of 336 active ingredients and 124 potential targets of mBHD associated with DN were identified. Among them, 8 hub genes were found to be important targets for mBHD in treating DN and were significantly correlated with the infiltration status of six immune cells. Partially, the active ingredients of mBHD demonstrated good stability in binding to CASP3 and TP53. mBHD treatment significantly reduced levels of total cholesterol, triglyceride, blood urea nitrogen, serum creatinine, and microalbumin in db/db mice. HE and Masson’s staining results showed that mBHD attenuated renal injury in db/db mice. Additionally, mBHD treatment could significantly alter the expression of CASP3, CCL2, TP53, ALB, and HMOX1.Conclusion: mBHD may be involved in the treatment of DN through multiple ingredients, targets, and pathways. In addition, mBHD could alleviate renal injury in db/db mice, possibly involving CASP3, CCL2, TP53, ALB, and HMOX1.Keywords: diabetic nephropathy, network pharmacology, molecular docking, traditional Chinese medicine

Jing-Feng Zou,&ast; Shao-Tian Li,&ast; Li-Ping Wang,&ast; Nian-Li Zhou, Jia-Jia Ran, Xin Yang, Chun-Hui Tian, Yi-Ting Liu, Yun Liu, Wen Peng Department of General Practice, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, WuHan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Liu; Wen Peng, Department of General Practice, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jie Fang Avenue, WuHan, Hubei, 1227, People’s Republic of China, Email 8735225@qq.com; pengwen666@sina.comBackground: Emerging evidence suggests that systemic inflammatory and nutritional biomarkers, along with derived indices, could serve as predictors for sarcopenia in cancer population. This study aimed to compare these predictors, focusing on the nutritional risk index (NRI) and evaluate its diagnostic value, for sarcopenic patients without cancer.Methods: This cross-sectional retrospective study included 1674 participants. Sarcopenia is defined by skeletal muscle mass index (SMI). Laboratory data reflected the values of systemic inflammatory and nutritional biomarkers, from which the derived indices were calculated. Multiple logistic regression analysis, ROC curve analysis, and the Youden index were utilized to assess the association between these markers and sarcopenia and determine the cutoff value for predicting sarcopenia.Results: Among all participants (1110 men and 564 women, mean age 61.97 ± 9.83 years), 398 individuals were diagnosed with sarcopenia, indicating a prevalence of 23.78% in China’s middle-aged and elderly population without cancer. Logistic regression analysis revealed significant associations between all biomarkers and derived indices with sarcopenia. Following adjustment for potential confounders, lower NRI values were significantly associated with a higher incidence of sarcopenia. For sarcopenia diagnosis, the area under the curve (AUC) for NRI was 0.769 ([95% CI, 0.742, 0.796], P < 0.001), with a cutoff value of 106.016, sensitivity of 75.6% and specificity of 66.1%. NRI demonstrated greater predictive advantage for sarcopenia incidence in men compared to women.Conclusion: A lower NRI value was associated with a higher prevalence of sarcopenia. NRI shows promise for early, rapid, and effective sarcopenia screening, particularly in China’s middle-aged and elderly male population without cancer.Keywords: sarcopenia, systemic inflammation, nutritional risk index, NRI

Xiuju Guan,1 Yue Liu,2 Yajuan An,1 Xinshuang Wang,1 Liping Wei,2 Xin Qi2 1School of Graduate Studies, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2Department of Cardiology, Tianjin Union Medical Center, Tianjin, People’s Republic of ChinaCorrespondence: Xin Qi, Email qixinx2011@126.comAbstract: Atherosclerosis (AS) is a chronic progressive inflammatory disease of the vascular wall and the primary pathological basis of cardiovascular and cerebrovascular disease. Focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2), two highly homologous members of the FAK family kinases, play critical roles in integrin signaling. They also serve as scaffolding proteins that contribute to the assembly of cellular signaling complexes that regulate cell survival, cell cycle progression, and cell motility. Research indicates that the FAK family kinases is involved in the gene regulation of vascular cells and that aberrant expression of this family is associated with pathological changes in vascular disease. These findings establish the FAK family kinases as a critical signaling mediator in atherosclerotic lesions and inhibition of its activity has the potential to attenuate the pathological progression of AS. This review highlights the indispensable role of the FAK family kinases in abnormal vascular smooth muscle cell proliferation, endothelial cell dysfunction, inflammation, and lipid metabolism associated with AS. We also summarize therapeutic targets against the FAK family kinases, providing valuable insights into therapeutic strategies for AS.Keywords: FAK family kinases, atherosclerosis, inhibitors, cellular signaling

Min Zhang,1– 3,&ast; Man Mi,1,2,4,&ast; Zilong Hu,3,4,&ast; Lixian Li,3,4 Zhiping Chen,1– 3 Xiang Gao,5 Di Liu,3,4 Bilian Xu,3 Yanzhi Liu1– 3 1Zhanjiang Key Laboratory of Orthopaedic Technology and Trauma Treatment, Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang, 524037, People’s Republic of China; 2Key Laboratory of Traditional Chinese Medicine for the Prevention and Treatment of Infectious Diseases, Guangdong Provincial Administration of Traditional Chinese Medicine (Central People’s Hospital of Zhanjiang), Zhanjiang, 524037, People’s Republic of China; 3Marine Medical Research Institute of Zhanjiang, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang, 524023, People’s Republic of China; 4Guangdong Provincial Key Laboratory for Research and Development of Natural Drug, School of Pharmacy, Guangdong Medical University, Zhanjiang, 524023, People’s Republic of China; 5Stem Cell Research and Cellular Therapy Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bilian Xu, Marine Medical Research Institute of Zhanjiang, School of Marine and Tropical Medicine, Guangdong Medical University, Zhanjiang, 524023, People’s Republic of China, Tel +86-0759-2388588, Email 124879846@qq.com Yanzhi Liu, Zhanjiang Key Laboratory of Orthopaedic Technology and Trauma Treatment, Zhanjiang Central Hospital, Guangdong Medical University, Zhanjiang, 524037, People’s Republic of China, Tel +86-0759-3157875, Email liuyanzhi02@163.comAbstract: Polydopamine is a versatile and modifiable polymer, known for its excellent biocompatibility and adhesiveness. It can also be engineered into a variety of nanoparticles and biomaterials for drug delivery, functional modification, making it an excellent choice to enhance the prevention and treatment of orthopedic diseases. Currently, the application of polydopamine biomaterials in orthopedic disease prevention and treatment is in its early stages, despite some initial achievements. This article aims to review these applications to encourage further development of polydopamine for orthopedic therapeutic needs. We detail the properties of polydopamine and its biomaterial types, highlighting its superior performance in functional modification on nanoparticles and materials. Additionally, we also explore the challenges and future prospects in developing optimal polydopamine biomaterials for clinical use in orthopedic disease prevention and treatment.Keywords: polydopamine, biomaterials, nanoparticles, bone, orthopaedics

Caige Li,1,2 Yu Xue,1 Yiwei Liu,1 Kangning Zheng,1 Yuting Gao,1,3 Yi Gong,1 Junlan Lu,1 Yuman Zhang,1 Jingmin Ji,1 Zhiqin Zhang,1 Xinli Shi1 1Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3School of Basic Medical Sciences, Shanxi University of Chinese Medicine, Jinzhong, Shanxi, People’s Republic of ChinaCorrespondence: Xinli Shi, Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, 3 Xingyuan Road, Shijiazhuang, Hebei, 050200, People’s Republic of China, Tel +86-0311-89926237, Email sxlsunshine@sina.comIntroduction: Yes-associated protein 1 (YAP1) is a crucial molecule in the Hippo pathway. The impact of hepatocyte-specific Yap1 knockout (Yap1LKO) on hepatic lipid droplets (LD) and pePLIN2 in metabolic fatty liver has not been reported. This study aims to explore whether Yap1LKO could offer a protective effect in a liver injury model.Methods: Three-week-old Yap1LKO and Yap1Flox mice were given aristolochic acid I (AAI) combined carbon tetrachloride (CCL4) establish liver injury model. Eight-week-old Yap1LKO and Yap1Flox mice were fed with a high-fat diet for 18 weeks to establish obesity-related liver injury model. Further biochemical, histomorphological, immunohistochemical, and lipidomic analyses were performed on serum and liver tissues of these mice to elucidate the effects of hepatocyte-specific Yap1 knockout on hepatic lipid metabolism.Results: Yap1LKO reduced triglyceride (TG) content and PLIN2 expression level in the liver during the intervention of AAI combined CCl4. Moreover, Yap1LKO improved lipid metabolism homeostasis in the liver by increasing the beneficial lipid molecules and reducing the harmful lipid molecules through lipidomics. Finally, Yap1LKO reduced TG content in the serum and liver, hepatic vacuolar degeneration, and hepatic PLIN2 expression level in mice fed with a high-fat diet (HFD).Conclusion: Yap1LKO is protective in regulating liver and blood TG when induced with toxic substances AAI combined CCl4 and a high-fat diet.Keywords: yes-associated protein, hepatocyte-specific Yap1 knockout, perilipin-2, lipidomic, triglyceride

Jun Wang,1 Yuan Liu,2 Guo-zhen Jin3 1Department of Cardiology, Hongze District People’s Hospital, Huaian, 223100, People’s Republic of China; 2Community Health Service Center of Huaihai Road, Nanjing, 210002, People’s Republic of China; 3Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People’s Republic of ChinaCorrespondence: Guo-zhen Jin, Email wjjinguozhen@126.comObjective: The success rate of polyvinyl alcohol (PAV) granules in the treatment of coronary artery perforation (CAP) was investigated to determine their safety and efficacy.Methods: Forty patients with II and III coronary artery perforations during percutaneous coronary intervention were divided into two groups. One group was only occluded by low pressure balloons (balloon occlusion group), and the other one was occluded with PVA granules during low-pressure balloon dilatation (PVA granules embolization group). Retrospective analysis of clinical data was used to compare the success rate and safety of various methods.Results: The balloon embolization group had 16 cases (88.9%) of coronary perforation type II and 2 cases (11.1%) of coronary perforation type III. The PVA granules embolization group had 20 cases (90.9%) of coronary perforation type II and 2 cases (9.1%) of coronary perforation type III. Of the 18 patients in the balloon occlusion group, 13 were immediately occluded, with a success rate of 72.2%, while the remaining 5 required embolization or covered stents. 6 of the 18 patients had pericardial effusion, and two of them underwent pericardiocentesis. Among the 22 patients in the PVA granules embolization group, 21 were immediately blocked, with a 95.5% success rate, while the other was occluded by a covered stent. The results revealed that the success rate of transcatheter closure in the PVA granules embolization group was significantly higher than that in the balloon embolization group, and the risk of pericardial effusion and pericardiocentesis in the PVA granules embolization group was significantly lower than that in the balloon embolization group.Conclusion: In comparison to the simple use of low-pressure balloon occlusion, the use of PAV granules in the treatment of II, III coronary artery perforation has a high success rate and safety, and is a viable method for treating coronary artery perforation.Keywords: percutaneous coronary intervention, coronary artery perforation, polyvinyl alcohol granules

Xiaoqin Wei,1,&ast; Fang Wang,2,&ast; Ying Liu,3 Zeyong Li,4 Zhong Xue,2 Mingyue Tang,5 Xiaowen Chen1 1School of Medical Imaging, North Sichuan Medical College, Nanchong City, Sichuan Province, People’s Republic of China; 2Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd, Shanghai, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Chengdu Medical College, Chengdu City, Sichuan Province, People’s Republic of China; 4Department of Radiology, Bishan Hospital of Chongqing Medical University, ChongQing, People’s Republic of China; 5Department of Physics, School of Basic Medicine, North Sichuan Medical College, Nanchong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaowen Chen, School of Medical Imaging, North Sichuan Medical College, 234 Fujiang Road, Nanchong City, Sichuan Province, People’s Republic of China, 637001, Email 56833804@qq.comPurpose: To predict the efficacy of patients treated with hepatectomy and transarterial chemoembolization (TACE) based on machine learning models using clinical and radiomics features.Patients and Methods: Patients with HCC whose first treatment was hepatectomy or TACE from June 2016 to July 2021 were collected in the retrospective cohort study. To ensure a causal effect of treatment effect and treatment modality, perfectly matched patients were obtained according to the principle of propensity score matching and used as an independent test cohort. Inverse probability of treatment weighting was used to control bias for unmatched patients, and the weighted results were used as the training cohort. Clinical characteristics were selected by univariate and multivariate analysis of cox proportional hazards regression, and radiomics features were selected using correlation analysis and random survival forest. The machine learning models (Deathhepatectomy and DeathTACE) were constructed to predict the probability of patient death after treatment (hepatectomy and TACE) by combining clinical and radiomics features, and an optimal treatment regimen was recommended. In addition, a prognostic model was constructed to predict the survival time of all patients.Results: A total of 418 patients with HCC who received either hepatectomy (n=267, mean age, 58 years ± 11 [standard deviation]; 228 men) or TACE (n=151, mean age, 59 years ± 13 [standard deviation]; 127 men) were recruited. After constructing the machine learning models Deathhepatectomy and DeathTACE, patients were divided into the hepatectomy-preferred and TACE-preferred groups. In the hepatectomy-preferred group, hepatectomy had a significantly prolonged survival time than TACE (training cohort: P < 0.001; testing cohort: P < 0.001), and vise versa for the TACE-preferred group. In addition, the prognostic model yielded high predictive capability for overall survival.Conclusion: The machine learning models could predict the outcomes difference between hepatectomy and TACE, and prognostic models could predict the overall survival for HCC patients.Keywords: radiomics, hepatocellular carcinoma, prognosis, hepatectomy

Yong Liu,1 Hui Liu,2 Queqiao Bian,1 Shuhuan Zhang,1 Yanmin Guan3 1Department of Dermatology & STD, The Third Central Hospital of Tianjin; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases; Artificial Cell Engineering Technology Research Center; Tianjin Institute of Hepatobiliary Disease, Tianjin, People’s Republic of China; 2Tianjin Institute of Hepatobiliary Disease, The Third Central Hospital of Tianjin, Tianjin, People’s Republic of China; 3Department of Tuberculosis, Tianjin Haihe Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Yong Liu, Department of Dermatology & STD, The Third Central Hospital of Tianjin; Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases; Artificial Cell Engineering Technology Research Center; Tianjin Institute of Hepatobiliary Disease, No. 83, Jintang Road, Hedong District, Tianjin, 300170, People’s Republic of China, Email liuyongtj@163.comBackground: Herpes zoster (HZ) and postherpetic neuralgia (PHN) significantly affect patients’ quality of life (QoL). Cultural differences may lead to different patient-reported outcomes across countries. The current study aims to evaluate the detrimental impact of HZ and PHN on QoL in China.Methods: This prospective study was conducted from January 2020 to April 2023. We used the Zoster Brief Pain Inventory (ZBPI) and 5-level EuroQol-5 Dimension (EQ-5D-5L) questionnaire to assess the QoL of HZ and PHN patients. Patients were required to complete the questionnaires at 15, 30, 60, and 90 days after the onset of the HZ rash. Additional questionnaires were administered at 120, 150, and 180 days for those who developed PHN within three months of the rash’s onset.Results: A cohort of 633 patients with a median age of 63 years were included in the study. The mean delay from the appearance of the initial HZ rash to the first medical consultation was 5.1 ± 2.8 days. Approximately 30% of the HZ patients (189/633) went on to develop PHN. For patients with HZ who did not progress to PHN, the ZBPI worst pain score and impaired QoL had nearly resolved by day 90 post-rash onset. Conversely, there was no significant improvement in the ZBPI worst pain score and QoL for those with PHN, even by day 180 post-rash onset.Conclusion: Both HZ and PHN significantly impaired patients’ QoL. However, the impairment caused by PHN was more severe in both intensity and duration.Keywords: herpes zoster, pain, post-herpetic neuralgia, quality of life

Yapu Liu, Yuanyuan Su, Zhonghao Luan, Xiuwei Hou, Guangliang Wu, Yonghui Xu, Songmao Wang, Lifeng Gao, Xiaochen Zheng Department of Spinal Surgery, Second Affiliated Hospital of Luohe Medical College, Luohe, People’s Republic of ChinaCorrespondence: Yapu Liu, Department of Spinal Surgery, Second Affiliated Hospital of Luohe Medical College, 463 Haihe Avenue, Luohe, 462300, People’s Republic of China, Tel/Fax +86-0395-6162312, Email 460547380@qq.comPurpose: To introduce the surgical methods and clinical results of percutaneous vertebroplasty (PVP) combined with hollow screw placement as a treatment for patients with Kummell’s disease and pedicle rupture.Methods: From January 2020 to January 2023, a total of 10 patients with Kummell’s disease and pedicle rupture confirmed via imaging underwent three-column intensive therapy using hollow screws combined with PVP. There were two males and eight females with an average age 75.7± 6.11 years old. The time of operation, bone cement injection amount, bone cement leakage during operation were recorded. X-ray and CT were reexamined after operation. The improvement in quality of life was assessed using the Oswestry Disability Index (ODI), and the improvement in low back pain was assessed using the visual analogue scale (VAS).Results: Hollow screw placement combined with PVP was successfully performed in all patients. The average operation time was 39.2± 5.1 min, and the average volume of bone cement injected was 5.85± 0.83mL. No leakage of bone cement into spinal canal occurred.The mean preoperative ODI score was 75.70± 4.39, but this decreased significantly postoperatively(P< 0.05), being 37.70± 6.95 at 1 day and 26.40± 4.90, 23.70± 4.87, 21.70± 5.46, and 20.50± 4.21 at 1, 3, 6, and 12 months after the operation, respectively. The mean VAS pain score before the operation was 8.35± 0.63, but the symptoms of back pain were significantly relieved after operation(P< 0.05). The mean VAS scores 1 day and 1, 3, 6, and 12 months after the operation were 3.45± 0.47, 2.55± 0.60, 1.89± 0.48, 1.50± 0.27, and 1.12± 0.20, respectively.Conclusion: Hollow screw placement combined with percutaneous vertebroplasty serves as a valuable three-column intensive treatment for patients with Kummell’s disease and pedicle rupture. This procedure has the advantages of minimal trauma, less pain and quick recovery. The strong anchoring of bone cement and hollow screws provides stable and firm healing conditions for vertebral and pedicle fractures.Keywords: three-column enhancement, PVP, hollow screw, Kummell’s disease, pedicle rupture

Lijuan Liang,1,&ast; Ming Jia,2,3,&ast; Min Zhao,4,&ast; Yiping Deng,5,&ast; Jun Tang,5 Xinghui He,2 Yilin Liu,2 Kexin Yan,2 Xin Yu,6 Hong Yang,7 Chunhong Li,2 Yao Li,2,8 Tao Li4 1Department of Pharmacy, Hejiang County People’s Hospital, Luzhou, Sichuan, People’s Republic of China; 2Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Nanchong Institute for Food and Drug Control, Nanchong, Sichuan, People’s Republic of China; 4Key Laboratory of Medical Electrophysiology of Ministry of Education, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Analysis and Testing Center, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 6Chinese Pharmacy Laboratory, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 7Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 8Science and Technology department, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yao Li; Tao Li, Email lnetyao@163.com; leta49@swmu.edu.cnAbstract: As a pivotal transition metal oxide, manganese dioxide (MnO2) has garnered significant attention owing to its abundant reserves, diverse crystal structures and exceptional performance. Nanosizing MnO2 results in smaller particle sizes, larger specific surface areas, optimized material characteristics, and expanded application possibilities. With the burgeoning research efforts in this field, MnO2 has emerged as a promising nanomaterial for tumor diagnosis and therapy. The distinctive properties of MnO2 in regulating the tumor microenvironment (TME) have attracted considerable interest, leading to a rapid growth in research on MnO2-based nanomaterials for tumor diagnosis and treatment. Additionally, MnO2 nanomaterials are also gradually showing up in the regulation of chronic inflammatory diseases. In this review, we mainly summarized the recent advancements in various MnO2 nanomaterials for tumor diagnosis and therapy. Furthermore, we discuss the current challenges and future directions in the development of MnO2 nanomaterials, while also envisaging their potential for clinical translation.Keywords: manganese dioxide nanoparticles, tumors, inflammation, biomedicine, research progress

Yang Liu,1 Lanxi Zhang,2 Jie Zhao,1,3 Ruilong Lu,1 Xuejie Shao,1 Kexin Xu,1 Jiansheng Li,1,3,4,&ast; Yange Tian1,3,&ast; 1Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province and Education Ministry of People’s Republic of China, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2School of Basic Medicine (Zhongjing School), Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 3Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 4First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiansheng Li; Yange Tian, Email li_js8@163.com; yange0910@126.comPurpose: The main objective of this study was to explore the mechanism of effective component compatibility of Bufei Yishen formula III (ECC-BYF III) in inhibiting mitochondrial oxidative stress in a rat model of chronic obstructive pulmonary disease (COPD).Methods: A549 cells exposed to cigarette smoke extract (CSE) were used to establish a model of mitochondrial oxidative damage. The cells were treated with the plasmid encoding Pkm2 and the enzymes and proteins involved in oxidative stress and mitochondrial function were measured. A rat model of COPD was established using CS and bacteria. Two different treatments were established, ECC-BYF III (5.5 mg/kg/d) and N-acetylcysteine (54 mg/kg/day). Animals were tested for pulmonary function (Vt, PEF, FVC, FEV0.1s and Cdyn) after eight weeks of therapy and were sacrificed. Pulmonary H&E staining was performed, and the total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) content were measured. The mitochondrial function was also examined. Furthermore, the Pkm2/Nrf2 signaling pathway was evaluated.Results: Overexpression of Pkm2 dramatically ameliorated the CS-induced mitochondrial oxidative damage. Further studies indicated that ECC-BYF III significantly improved mitochondrial function and inhibited oxidative stress in the lung tissues of COPD rats. Moreover, it can upregulate mitochondrial respiratory chain enzyme activity. ECC-BYF III also decreased the MDA content and increased T-SOD, GSH-Px, and T-AOC expression to facilitate oxidative homeostasis. Finally, our results indicated that the Pkm2/Nrf2 pathway is regulated by ECC-BYF III in A549 cells and lung tissue.Conclusion: These results indicate that ECC-BYF III exerts a strong effective therapeutic effect against cigarette smoke combined with bacteria-induced COPD in rats by activating the Pkm2/Nrf2 signaling pathway and restoring mitochondrial oxidative stress. Although more in vivo animal model research is needed to confirm these findings, this study contributes new data to support the conventional usage of ECC-BYF III.Keywords: chronic obstructive pulmonary disease, oxidative stress, ECC-BYF III, Pkm2, Nrf2

Zaifeng Si,1,2,&ast; Shengmei Zhao,3,&ast; Yingying Hao,3 Qian Wang,3 Yanfa Zhong,2 Yue Liu,3 Ran Chen,3 Yan Jin,3 Zhiming Lu1,3 1Department of Clinical Laboratory, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Clinical Laboratory, Dezhou Municipal Hospital of Traditional Chinese Medicine, Dezhou, Shandong, People’s Republic of China; 3Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Jin; Zhiming Lu, Email sdjinyan@163.com; luzhiming@sdu.edu.cnBackground: Enterobacter cloacae complex (ECC), which includes major nosocomial pathogens, causes urinary, respiratory, and bloodstream infections in humans, for which colistin is one of the last-line drugs.Objective: This study aimed to analyse the epidemiology and resistance mechanisms of colistin-resistant Enterobacter cloacae complex (ECC) strains isolated from Shandong, China.Methods: Two hundred non-repetitive ECC strains were collected from a tertiary hospital in Shandong Province, China, from June 2020 to June 2022. Whole-genome sequencing and bioinformatics analyses were performed to understand the molecular epidemiology of the colistin-resistant ECC strains. The nucleotide sequences of heat shock protein (hsp60) were analyzed by using BLAST search to classify ECC. The gene expression levels of ramA, soxS, acrA, acrB, phoP, and phoQ were assessed using RT-qPCR. MALDI-TOF MS was used to analyse the modification of lipid A.Results: Twenty-three colistin-resistant strains were detected among the 200 ECC clinical strains (11.5%). The hsp60 cluster analysis revealed that 20 of the 23 ECC strains belonged to heterogeneous resistance clusters. Variants of mgrB, phoPQ, and pmrAB, particularly phoQ and pmrB, were detected in the 23 ECC strains. The soxS and acrA genes were significantly overexpressed in all 23 colistin-resistant ECC strains (P < 0.05). Additionally, all 23 ECC strains contained modified lipid A related to colistin resistance, which showed five ion peaks at m/z 1876, 1920, 1955, 2114, and 2158. Among the 23 ECC strains, 6 strains possessed a phosphoethanolamine (pETN) moiety, 16 strains possessed a 4-amino-4-deoxy-L-arabinose (−L-Ara4N) moiety, and one strain had both pETN and −L-Ara4N moieties.Conclusion: This study suggests that diverse colistin resistance existed in ECC, including unknown resistance mechanisms, exist in ECC. Mechanistic investigations of colistin resistance are warranted to optimise colistin use in clinical settings and minimise the emergence of resistance.Keywords: Enterobacter cloacae complex, ECC, epidemiology, colistin, resistance mechanism

Wei Sun,1,&ast; Yun Liu,2,&ast; Li Wang3 1Department of Oncology, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 2Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 3Department of Oncology, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Wang, Department of Oncology, Beijing Luhe Hospital, Capital Medical University, No. 82, Xinhua South Road, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel +86 18010279916, Email lhyywl@163.comObjective: This study aimed to investigate the feasibility of the efficacy and safety of TACE combined with Lenvatinib and PD-1 blockade in HCC with portal vein tumor thrombus (PVTT).Methods: Patients with HCC and PVTT who underwent TACE combined with Lenvatinib and PD-1 blockade as first-line therapy in clinical practice were retrospectively included. All subjects were followed-up regularly to obtain prognostic outcomes. The safety profile observed during the combination therapy was collected and documented. The Log rank test was used for exploratory analysis of prognosis and baseline characteristics and Cox regression analysis was used for multivariate analysis.Results: A total of 67 HCC patients with PVTT who received TACE combined with Lenvatinib and PD-1 blockade were included in this study. The best therapeutic response during treatment suggested that 4 patients achieved complete response, 30 patients showed partial response, 25 patients were stable disease, 5 patients had disease progression and 3 patients were not available. Objective response rate of this regimen was 50.7% [95% confidence interval (CI): 38.2– 63.2%] and disease control rate was 88.1% (95% CI: 77.8– 94.7%). The median progression-free survival of 67 HCC patients with PVTT who received TACE combined with Lenvatinib and PD-1 blockades was 9.3 months (95% CI: 5.85– 12.75), and the median overall survival was 24.4 months (95% CI: 19.11– 29.69). The safety profile highlighted that 65 patients experienced adverse reactions regardless of grade during treatment (97.0%), among whom 34 patients were deemed as grade ≥ 3 adverse reactions (50.7%). The most common adverse reactions were hypertension, fatigue, abnormal liver function, nausea, vomiting, and diarrhea. Overall adverse reactions were acceptable and controllable.Conclusion: TACE combined with Lenvatinib and PD-1 blockades as first-line therapy for HCC with PVTT demonstrated potential feasibility and encouraging clinical outcomes, providing long-term survival benefits for HCC patients. This conclusion should be confirmed in prospective large-scale clinical trials.Keywords: hepatocellular carcinoma, portal vein tumor thrombus, TACE, Lenvatinib, PD-1 blockades, efficacy, safety

Zhangnan Sun,1,&ast; Ji Shi,2,&ast; Chaolei Liu,1 Jingjing Zhang,1 Yue Liu,1 Yini Wu,3 Xin Han,3 Hong Dai,3 Jimin Wu,3 Lijun Bo,1 Faxing Wang3 1Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Anesthesiology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Anesthesiology, Lishui People’s Hospital, Lishui Hospital of Wenzhou Medical University, Lishui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Faxing Wang, Department of Anesthesiology, Lishui People’s Hospital, Lishui Hospital of Wenzhou Medical University, No. 15, Dazhong Street, Lishui, Zhejiang Province, 323000, People’s Republic of China, Email wfx2023@wmu.edu.cn Lijun Bo, Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email 27901566@hebmu.edu.cnObjective: This study investigates the effect of low-dose dexmedetomidine infusion on perioperative neurocognitive function in elderly patients undergoing endoscopic retrograde cholangiopancreatography (ERCP).Patients and Methods: This double-blind trial enrolled 80 elderly ERCP patients randomized to receive dexmedetomidine (Group D) or placebo (Group S). Group D received dexmedetomidine at 0.4 μg·kg− 1·h− 1 starting 15 minutes before surgery until completion, along with propofol at 1.5 mg/kg for anesthesia. Group S received saline and propofol in a similar manner. Anesthesia was maintained with dexmedetomidine at 0.4 μg·kg− 1·h− 1 and propofol at 1– 2 mg/kg during surgery. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) preoperatively and on postoperative days 1, 3, and 5. Primary outcome was perioperative neurocognitive disorder (PND) incidence on day 5; secondary outcomes included changes in perioperative IL-6, cortisol, S100-β, hemodynamics, anesthesia parameters, postoperative pain, agitation scores, and adverse events.Results: All 80 patients completed the trial. On postoperative day 5, the cumulative probability of PND incidence was significantly lower in Group D than in Group S (12.5% vs 35%, P=0.018). Group D also had lower levels of IL-6 (F=199.472, P< 0.001), S100-β (F=2681.964, P< 0.001), and cortisol (F=137.637, P< 0.001). Propofol doses were lower in Group D (706.1 ± 202.4 vs 1003.3 ± 203.7, P< 0.001), and bradycardia rates were higher (45% vs 15%, P=0.003), though atropine use did not significantly differ between groups. Group D showed greater stability in mean arterial pressure. Postoperative complications and adverse reactions were similar across groups.Conclusion: Perioperative low-dose dexmedetomidine infusion with propofol in elderly ERCP patients ensures safe and effective monitored anesthesia care (MAC), reducing PND incidence by mitigating peripheral inflammation and stress responses. Long-term follow-up is needed to fully evaluate PND incidence.Keywords: ERCP, PND, dexmedetomidine, elderly patients

Aiben Kayierhan,1,2,&ast; Abuduwupuer Haibier,1,2,&ast; Aikebaierjiang Aisaiti,1,2,&ast; Alimujiang Aximu,1,2 Liang Ma,1,2 Yuntao Liu,1,2 Tuerhongjiang Abudurexiti1,2 1Minimally Invasive Spine Surgery, Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, People’s Republic of China; 2Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tuerhongjiang Abudurexiti, Email 2676661815@qq.comObjective: To evaluate the clinical effectiveness of endoscopic removal of spinal infections and posterior pedicle surgery, including bone grafting, fixation, and chemotherapy, and to outline preventive strategies for complications, offering guidance for clinical practice.Methods: 128 spinal infectious disease patients (2018– 2022) were categorized into Group A (endoscopic removal, n=44) and Group B (posterior pedicle removal+bone grafting+fixation, n=84). Pre-surgery, all received quadruple antibiotic therapy. Metrics tracked: operation time, blood loss, drainage, recovery, stay, transfusion, complications, and pre/post-surgery VAS, ODI, ESR, CRP, PCT, D-dimer, NLR, Hb, albumin.Results: (1) Preoperative data: There were no statistically significant differences in age, gender, body mass index, involved segments, past medical history (cardiovascular and cerebrovascular diseases, respiratory diseases, endocrine system diseases, metabolic diseases and tuberculosis), smoking history, preoperative erythrocyte sedimentation rate, C-reactive protein, procalcitonin, D-dimer, lymphocyte and neutrophil-lymphocyte ratio, hemoglobin, total protein, waist VAS score and waist ODI score (P> 0.05). (2) The main postoperative indexes were significantly lower than those of group B at the last follow-up at 3 months and the last follow-up in group A, and the difference was significant (P< 0.05), the hemoglobin and total protein in group A were significantly higher than those in group B at the last postoperative follow-up (P< 0.05), and the recurrence rate in group B was significantly higher than that in group A, and the difference was significant (P=0.048). (3) Postoperative secondary indicators: the amount of blood transfusion in group A was significantly lower than that in group B, and the difference between the two groups was statistically significant (P< 0.05), while the operation time, intraoperative blood loss and postoperative hospital stay in group A were significantly smaller than those in group B, and the difference between the two groups was statistically significant (P< 0.05).Conclusion: Endoscopic lesion removal for spinal infections achieves similar safety to posterior pedicle surgery, with shorter operation time, less blood loss, lower recurrence, and reduced drainage. It enhances ESR, spine function, and pain relief, meriting promotion.Keywords: spinal infectious diseases, lesion removal, spinal tuberculosis, brucellosis, drug chemotherapy

Yanhong Liu, Dongyun Jia, Lin Li, Meiyan Wang Center for Prenatal Diagnosis, Center for Reproductive Medicine, First Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Meiyan Wang, Email wangmeiyan0426@jlu.edu.cnAbstract: The endometrium is an extremely important component of the uterus and is crucial for individual health and human reproduction. However, traditional methods still struggle to ideally repair the structure and function of damaged endometrium and restore fertility. Therefore, seeking and developing innovative technologies and materials has the potential to repair and regenerate damaged or diseased endometrium. The emergence and functionalization of various nanomedicine and biomaterials, as well as the proposal and development of regenerative medicine and tissue engineering techniques, have brought great hope for solving these problems. In this review, we will summarize various nanomedicine, biomaterials, and innovative technologies that contribute to endometrial regeneration, including nanoscale exosomes, nanomaterials, stem cell-based materials, naturally sourced biomaterials, chemically synthesized biomaterials, approaches and methods for functionalizing biomaterials, as well as the application of revolutionary new technologies such as organoids, organ-on-chips, artificial intelligence, etc. The diverse design and modification of new biomaterials endow them with new functionalities, such as microstructure or nanostructure, mechanical properties, biological functions, and cellular microenvironment regulation. It will provide new options for the regeneration of endometrium, bring new hope for the reconstruction and recovery of patients’ reproductive abilities. Keywords: nanomedicine, biomaterials, endometrium, regeneration, stem cells

Roumei Wang,1,&ast; Shien Fu,2,&ast; Rui Huang,3,&ast; Chengcheng Qiu,1 Yunxia Tang,1 Yaoli Liu1 1Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3College of Public Hygiene of Guangxi Medical University, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yaoli Liu, Department of Medical Ultrasound, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Tel +86-771-5356706, Email 100youngly@163.comObjective: This study aimed to evaluate the quadriceps femoris in patients with chronic thyrotoxic myopathy (CTM) using musculoskeletal ultrasound and to explore its practical clinical value for the diagnosis of CTM.Methods: A total of 241 subjects recruited from the First Affiliated Hospital of Guangxi Medical University were surveyed for detailed medical history and underwent grip strength tests, fixed-distance walking, and quadriceps femoris ultrasound examinations. Differences in muscle parameters between the CTM, non-CTM, and healthy groups were analyzed. An Receiver operating characteristic (ROC) curve was established to analyze the predictive value of various ultrasound measurements for CTM, and Spearman correlation analysis and binary logistic regression were applied to explore the factors associated CTM.Results: The quadriceps femoris contraction index, muscle thickness, muscle cross-sectional area, and pennation angle in the CTM group were significantly lower than those in the non-CTM and healthy groups (p< 0.01). The ROC curve prediction showed that the pennation angle had the best sensitivity and specificity for diagnosing myogenesis, with an area under the curve of 89%. Moreover, the pennation angle of the CTM group was positively correlated with step speed (r=0.245, p=0.031) and body surface area (r=0.276, p=0.014), but negatively correlated with age (r=− 0.306, p=0.007). Regression analysis showed that the quadriceps femoris contraction index, muscle thickness, pennation angle, and cross-sectional area were factors that related the CTM. After adjusting for potential confounding factors, the association between Muscle Bundle Length and CTM became significant (OR=1.99, 95% CI: 1.22, 3.35, p=0.007). Muscular echo in patients was observed to varying degrees of enhancement.Conclusion: Musculoskeletal ultrasonography in the quantitative analysis of muscle parameters and muscle echo of the quadriceps femoris can provide essential imaging evidence for predicting CTM.Keywords: chronic thyrotoxic myopathy, musculoskeletal ultrasound, muscle echo intensity, Heckmatt Scale

Ying Wang,1,&ast; Xuelong Li,2,&ast; Yakun Gao,2 Xun Zhang,3 Yiyi Liu,3 Qing Wu1,3 1Department of Psychiatry, Affiliated Psychological Hospital of Anhui Medical University, Anhui Mental Health Center, Hefei Fourth People’s Hospital, Hefei, Anhui, People’s Republic of China; 2Qingdao Mental Health Center, Qingdao, Shandong, People’s Republic of China; 3School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Wu, Department of Psychiatry, Affiliated Psychological Hospital of Anhui Medical University, Hefei Fourth People’s Hospital, 316 Huangshan Road, Hefei, 230022, People’s Republic of China, Tel +86-13856919530, Email wuqinghf@163.comPurpose: The co-morbidity of non-alcoholic fatty liver disease (NAFLD) in patients with bipolar disorder (BD) has a negative impact on patient treatment and prognosis. This study aimed to identify the prevalence of NAFLD in patients with BD and investigate the risk factors of NAFLD.Patients and Methods: A total of 678 patients with BD were included in the study. Clinical data were obtained from the hospital’s electronic health record system. Data included fasting blood glucose, alanine aminotransferase, triglycerides, aspartate aminotransferase, high-density lipoprotein cholesterol (HDL), alkaline phosphatase, total cholesterol, glutamine transpeptidase, uric acid, apolipoprotein A1, apolipoprotein B, and liver ultrasound findings.Results: The prevalence of NAFLD was 43.66% in patients with BD. Significant differences in body mass index (BMI), mean age, diabetes prevalence, course of BD, fasting blood glucose, alanine aminotransferase, HDL, alkaline phosphatase, triglycerides, aspartate aminotransferase, uric acid, glutamine transpeptidase, apolipoprotein B, total cholesterol, and apolipoprotein A1 were seen between the groups (all P< 0.01). Male sex, age, BMI, course of BD, alanine aminotransferase, fasting blood glucose, aspartate aminotransferase, diabetes, glutamine transpeptidase, total cholesterol, alkaline phosphatase, triglycerides, uric acid, apolipoprotein B, HDL, and apolipoprotein A1 levels were correlated with NAFLD (all P< 0.05). In patients with BD, diabetes (OR=6.412, 95% CI=1.049− 39.21), BMI (OR=1.398, 95% CI=1.306− 1.497), triglycerides (OR=1.456, 95% CI=1.036− 2.045), and apolipoprotein A1 (OR=0.272, 95% CI=0.110− 0.672) were risk factors for NAFLD (all P< 0.05).Conclusion: Risk factors for NAFLD in patients with BD include diabetes, BMI, course of BD, and a low level of apolipoprotein A1. A proactive approach to disease management, such as appropriate physical activity and adoption of a healthy diet, and regular monitoring of changes in patient markers should be adopted to reduce the prevalence of NAFLD.Keywords: China, comorbidity, Psychiatry

Tong Chen,1– 4 Yu Liu,2,3 Shiquan Wu,2 Siyu Long,2 Ling Feng,4,5 Wenqian Lu,6 Wenya Chen,2 Guoai Hong,2 Li Zhou,2 Fang Wang,2 Yuechan Luo,2 Hequn Zou,2,4,6 Weihua Liu7 1Department of Nephrology, Chongqing Key Laboratory of Prevention and Treatment of Kidney Disease, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, People’s Republic of China; 2South China Hospital of Shenzhen University, Shenzhen, 518116, People’s Republic of China; 3Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National Regional Key Technology Engineering Laboratory for Medical Ultrasound School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, People’s Republic of China; 4Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 5Department of Nephrology, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 6School of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China; 7Department Nephrology of Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fujian, 350001, People’s Republic of ChinaCorrespondence: Weihua Liu, Department Nephrology of Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fujian, 350001, People’s Republic of China, Email lwh10280465@163.com Hequn Zou, School of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China, Email zouhequn@cuhk.edu.cnBackground: Obesity and insulin resistance (IR) are positively associated with chronic kidney disease (CKD). Previous studies have identified triglyceride-glucose index (TyG) as a valuable surrogate of insulin resistance. Recently, new indicators combining TyG and simple anthropometric indices have emerged, The objective of this study was to assess the diagnostic accuracy of TyG and newly TyG related indicators in detecting CKD and explore which indices were superior in associating with CKD in Chinese population.Methods: Correlation test, logistic regression analysis, and receiver operating characteristic (ROC) analyses were used to evaluate the optimal cut-off and value of TyG, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), TyG-waist to height ratio (TyG-WHtR) for predicting CKD.Results: TyG-WHtR, TyG-WC, and TyG-BMI correlated with several risk factors for CKD. After adjusting for confounders, TyG-WHtR and TyG-WC remained significantly associated with CKD, while TyG-BMI did not. The highest quartiles of TyG-WHtR and TyG-WC had 1.95- and 1.91-fold increased risk of CKD than the lowest quartiles (P< 0.05). TyG-WHtR had the largest AUC (0.687) for CKD detection, followed by TyG-WC (0.669), TyG (0.652), and TyG-BMI (0.648). A united model that involved TyG-WHtR and other risk variables had higher predictive performance (AUC=0.791) than a single TyG related indicator. However, TyG had the highest OR (2.713, 95% CI, 1.446– 5.090) for reduced eGFR in the fully adjusted model. A united model that involved TyG and WHtR separately had stronger predictive ability (AUC: 0.794) than the model that involved TyG-WHtR individually (AUC:0.791).Conclusion: This study found that TyG-WHtR had a better diagnostic value in the diagnosis of CKD, compared to other TyG related indicators, but none of the TyG related indicators showed a stronger association with CKD than TyG. Further research and more refined algorithms are needed to verify these new indicators.Keywords: chronic kidney disease, insulin resistance, obesity, TyG related indicators

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

Liming Qin,1,2,&ast; Moqin Qiu,3,&ast; Jingmei Tang,2 Shuyan Liu,4 Qiuling Lin,5 Qiongguang Huang,2 Xiaoxia Wei,5 Qiuping Wen,1 Peiqin Chen,6 Zihan Zhou,7 Ji Cao,7 Xiumei Liang,8 Qian Guo,9 Cunli Nong,9 Yizhen Gong,5 Yuying Wei,1 Yanji Jiang,10 Hongping Yu,1,2,11– 13 Yingchun Liu1 1Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2School of Public Health, Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 4Key Laboratory of Biological Molecular Medicine Research, Education Department of Guangxi Zhuang Autonomous Region, Guangxi Medical University, Nanning, People’s Republic of China; 5Department of Clinical Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 6Editorial Department of Chinese Journal of Oncology Prevention and Treatment, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 7Department of Cancer Prevention and Control, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 8Department of Disease Process Management, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 9Liuzhou Worker’s Hospital, Liuzhou, People’s Republic of China; 10Department of Scientific Research, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 11Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Guangxi Medical University, Nanning, People’s Republic of China; 12Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, People’s Republic of China; 13Key Cultivated Laboratory of Cancer Molecular Medicine of Guangxi Health Commission, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingchun Liu; Hongping Yu, Department of Experimental Research, Guangxi Medical University Cancer Hospital, 71&num; Hedi Road, Qingxiu District, Nanning, People’s Republic of China, Tel +86-15877191237 ; +86-771-5330850, Fax +86-771-5312000, Email liuyingchun@stu.gxmu.edu.cn; yuhongping@stu.gxmu.edu.cnPurpose: P53 is a suppressor gene closely related to carcinogenesis. However, the associations between genetic variants in the p53 signaling pathway and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unknown. The current study aims to analyze associations between the single nucleotide polymorphisms (SNPs) in p53 pathway-related genes and survival of patients with HBV-HCC.Methods: We evaluated the associations between 4698 SNPs in 70 genes of the p53 pathway and overall survival (OS) of 866 patients in additive genetic models by using Cox proportional hazards regression analysis. Stepwise multivariable Cox regression analysis was conducted to determine the independent effects of identified SNPs in single-locus analyses. The expression of quantitative trait loci (eQTL) was also analyzed using data from GTEx and 1000 Genomes Project, and functional prediction of SNPs was performed by using RegulomeDB v2.2, 3DSNP v2.0, HaploReg v4.2 and VannoPortal.Results: We found that two novel SNPs of CD82 rs7925603 A > G and PMAIP1 rs4396625 A > T, were significantly and independently associated with OS [adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were 1.27 (1.10– 1.48) and 0.77 (0.66– 0.91), respectively; P = 0.001 and = 0.002, respectively] and that the combined risk genotypes of these SNPs showed a significant association with OS in patients with HBV-HCC (Ptrend < 0.001). Further eQTL analysis in the GTEx dataset showed that the rs7925603 G allele was associated with lower CD82 mRNA expression levels, while the rs4396625 T allele was associated with higher PMAIP1 mRNA expression levels in whole blood cells.Conclusion: We identified two observed survival-associated SNPs in CD82 and PMAIP1 in the p53 pathway, which influenced HBV-HCC survival possibly through a mechanism of altering mRNA expression. Large studies are warranted to validate our findings.Keywords: hepatocellular carcinoma, hepatitis B virus, p53 signaling pathway, genetic variants, survival

Cong Peng,1 Yan Liu,2 Yuqin Zhou,3 Zhenyun Zhang4 1School of Education and Psychology, Hubei Engineering University, Xiaogan, 432000, People’s Republic of China; 2School of Education, Hunan University of Science and Technology, Xiangtan, 411201, People’s Republic of China; 3School of Foreign Languages, Hubei Engineering University, Xiaogan, 432000, People’s Republic of China; 4School of Computer and Information Science, Hubei Engineering University, Xiaogan, 432000, People’s Republic of ChinaCorrespondence: Cong Peng; Zhenyun Zhang, Email pengcong2023@hbeu.edu.cn; 3132980866@qq.comBackground: Adolescent anxiety is closely associated with the quality of parent-child attachment. However, previous studies have predominantly focused on the impact of mother-child attachment. Little is known about the direct and indirect associations of father-child attachment on adolescent anxiety.Purpose: This study aims to investigate the association and underlying mechanisms that link father-child attachment and adolescent anxiety. A bidirectional chain mediating model was constructed to test whether neuroticism and peer attachment play bidirectional mediating roles in father-child attachment and adolescent anxiety.Methods: The proposed model was examined among 763 adolescents aged 11− 16 years (male 53.1%) from four middle schools in Central China. Students completed questionnaires on father-child attachment, anxiety, neuroticism and peer attachment. The correlation and bidirectional chain mediating effect analyses were conducted using SPSS Process.Results: (1) Father-child attachment negatively correlated with adolescent anxiety and neuroticism, and positively correlated with peer attachment; (2) Father-child attachment had an indirect association on adolescent anxiety through three pathways: a partial mediating effect on neuroticism, a partial mediating effect on peer attachment, and a bidirectional chain mediating effect involving both neuroticism and peer attachment.Conclusion: This study revealed father-child attachment has an indirect association with adolescent anxiety through the bidirectional chain mediation of neuroticism and peer attachment. These empirical findings shed light on the intricate dynamic between father-child attachment and anxiety among Chinese adolescents, highlighting the crucial role of fathers in the prevention and reduction of adolescent anxiety from the perspectives of father-child dynamics, personal traits, and interpersonal relationships.Keywords: father-child attachment, adolescent anxiety, neuroticism, peer attachment, bidirectional chain mediating effect

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

Chunliu Hou,1,&ast; Ying Liu,2,&ast; Xuesen Su,1 Shouyuan Tian,1 Yan Li1,2 1College of Anesthesia, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Anesthesiology, Tianjin Jizhou People’s Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shouyuan Tian; Yan Li, Email chinatsyjj@sxmu.edu.cn; drliyan@163.comBackground: Due to the global prevalence of opioid drugs, postsurgical prescriptions can lead to substantial opioid consumption, highlighting the increasing need for alternative medications. Alternative medicines can markedly lessen the usage of opioids after surgery, but the variety and notable side effects of these alternatives require meticulous experimental support.Objective: This study explored the efficacy and safety of ulinastatin for alleviating postsurgical pain, for reducing the need for opioids, and for inclusion in conventional treatment methods.Methods: A total of 108 patients undergoing elective hip replacement were randomly allocated into either the experimental group (56 cases, standard pain relief treatment plus 60 IU ulinastatin) or the control group (40 cases, standard pain relief treatment). The main outcomes measured were the total consumption of opioids at 24, 48, and 72 h postoperatively. Secondary outcomes comprised patient-reported pain indices and levels of satisfaction with pain control. The frequency of adverse events evaluated medication safety.Results: There were no statistically significant differences in age, sex, or underlying diseases between the two groups. Over 24 hours, opioid consumption was higher in the standard treatment group (66.6 mg; mean difference [MD]: 4.43 mg; 95% CI: 57.6– 75.5) than in the intervention group (54.5 mg; MD: 1.91 mg; 95% CI: 50.7– 58.3). The standard treatment group exhibited a notably higher incidence of adverse reactions. However, there was no disparity in post-discharge satisfaction between the groups, with an odds ratio of 1.058 (95% CI: 0.62– 1.82; P > 0.05). Additionally, significant differences in C-reactive protein levels were observed immediately and 6 h after surgery between the two groups.Conclusion: Within 72 h post-surgery, ulinastatin was effective in substantially reducing the use of opioids while maintaining adequate pain control. Ulinastatin may be beneficial for postoperative pain management and for reducing the risks associated with opioid use.Registered: ClinicalTrials.gov ChiCTR2300072126.Keywords: ulinastatin, postoperative pain, pain management, opioid

Zhuoran Li,1,&ast; Yirui Zhai,1,&ast; Fan Wu,2,&ast; Dayong Cao,2,&ast; Feng Ye,3,&ast; Yan Song,4 Shulian Wang,1 Yueping Liu,1 Yongwen Song,1 Yuan Tang,1 Hao Jing,1 Hui Fang,1 Shunan Qi,1 Ningning Lu,1 Ye-Xiong Li,1 Jianxiong Wu,2 Bo Chen1 1State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China; 2Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China; 3Department of Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China; 4Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Chen, State Key Laboratory of Molecular Oncology, Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China, Tel +86-10-87788280, Email chenboo@outlook.com Jianxiong Wu, Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, People’s Republic of China, Tel +86-10-87781700, Email Dr_wujx@163.comPurpose: This study evaluated the clinical outcomes of patients with hepatocellular carcinoma (HCC) with hepatic vein tumor thrombus (HVTT) and/or inferior vena cava tumor thrombus (IVCTT) receiving radiotherapy (RT) combined with systemic therapies.Patients and Methods: Patients with HCC with HVTT and/or IVCTT who received RT were identified at our institution. The prescription doses were 30– 65 Gy for planning target volume and 40– 65 Gy for the gross tumor volume. Targeted therapy and immune checkpoint inhibitors were used concurrently if patients were at a high risk of or already had distant metastasis. After RT completion, follow-up was performed at 1, 3, 6, and 12 months, and 3 to 6 months thereafter. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and toxicity were recorded.Results: Thirty-four patients were retrospectively enrolled between January 2016 and September 2021. Most patients received concurrent targeted therapy (70.6%) and/or post-RT (79.4%). The in-field ORR and disease control rates were 79.4% and 97.1%, respectively. The OS rates were 77.6% at 1 year and 36.3% at 2 years (median OS, 15.8 months). The median PFS and median in-field PFS were 4.2 months and not reached, respectively. The PFS and in-field PFS rates were 24.6% and 79.2% at 1 year, 19.7% and 72.0% at 2 years, respectively. An alpha-fetoprotein level > 1000 ng/mL was a significant prognostic factor for worse OS (HR, 5.674; 95% CI, 1.588– 20.276; p=0.008); in-field complete/partial response was a significant prognostic factor for better OS (HR, 0.116; 95% CI, 0.027– 0.499; p=0.004). The most common site of first failure was the lungs (13/34 patients, 38.2%), followed by the liver (7/34 patients, 20.6%). No patients developed radiation-induced liver disease or pulmonary embolism during follow-up.Conclusion: Combining RT and systemic therapy was safe and effective in treating patients with HCC with HVTT and IVCTT.Keywords: liver cancer, immunotherapy, systemic therapy, radiation therapy

Lili Huang,1,&ast; Yesong Liu,2,&ast; Tingting Geng,1,&ast; Nannan Zhang,2 Liang Sun,1 Shouling Wu,3 Xiang Gao1 1Department of Nutrition and Food Hygiene, School of Public Health, Institute of Nutrition, Fudan University, Shanghai, People’s Republic of China; 2Department of Neurology, Kailuan General Hospital, Tangshan, People’s Republic of China; 3Department of Cardiology, Kailuan General Hospital, Tangshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Gao, Department of Nutrition and Food Hygiene, School of Public Health, Institute of Nutrition, Fudan University, 130 Dongan Road, Shanghai, 200032, People’s Republic of China, Email xiang_gao@fudan.edu.cn Shouling Wu, Department of Cardiology, Kailuan General Hospital, 57 Xinhua East Road, Tangshan, 063000, People’s Republic of China, Tel +86 315 3025655, Fax +86 315 3725312, Email drwusl@163.comBackground: Sleep complaints were reported to be associated with stroke, however, the evidence on the association between healthy sleep pattern and stroke risk in Chinese is limited.Objective: The aim of this study was to investigate the association between healthy sleep pattern and stroke in Chinese, and the influence of metabolic diseases on the association.Methods: A total of 11,851 participants from the Kailuan study in China without stroke at baseline were included. We calculated a healthy sleep score according to four sleep factors, and defined the low-risk groups as follows: no insomnia, no excessive daytime sleepiness, no frequent snoring, and sleep 7– 8h/d. Each low-risk sleep factor was assigned a score of 1. Cox proportional hazard models were used to assess the association between healthy sleep score and stroke. Mediation analysis was used to estimate the role of metabolic diseases (obesity, diabetes, and hypertension) in the healthy sleep score-stroke association.Results: During a mean follow-up period of 7.7 years, 504 cases of stroke were identified. A higher healthy sleep score was associated with a lower risk of stroke in a dose-response manner (P-trend=0.03). The adjusted hazard ratio (HR) for participants with a healthy sleep score of 4 versus ≤ 2 was 0.75 (95% confidence interval [CI]: 0.56, 0.96). In addition, obesity, diabetes, and hypertension collectively explained 21.9% (95% CI: 17.2, 26.5) of the association between healthy sleep score and stroke.Conclusion: Adherence to healthy sleep pattern was associated with a lower risk of stroke, and the favorable association was partially mediated by metabolic diseases.Keywords: healthy sleep pattern, metabolic disease, stroke, mediation

Demeng Xia,1,2,&ast; Qingqing Qian,1,&ast; Sheng Wang,3,&ast; Xiao Dong,4 Ying Liu5 1Department of Pharmacy, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, 200240, People’s Republic of China; 2Department of Pharmacy, Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, 200120, People’s Republic of China; 3Department of Traumatic Orthopedics, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200434, People’s Republic of China; 4School of Medicine, Shanghai University, Shanghai, 200444, People’s Republic of China; 5Institute of Translational Medicine, Shanghai University, Shanghai, 200444, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Liu; Xiao Dong, Email liuchanger1984@163.com; dong-xiao@shu.edu.cnIntroduction: Osteoporosis, characterized by dysregulation of osteoclastic bone resorption and osteoblastic bone formation, severely threatens human health during aging. However, there is still no good therapy for osteoporosis, so this direction requires our continuous attention, and there is an urgent need for new drugs to solve this problem.Methods: Traditional Chinese Medicine Salvia divinorum monomer pomolic acid (PA) could effectively inhibit osteoclastogenesis and ovariectomized osteoporosis. However, its poor solubility and lack of targeting severely limits its further application. A novel bone-targeting nanomedicine (PA@TLipo) has been developed to reconstruct the osteoporotic microenvironment by encapsulating pomolic acid in alendronate-functionalized liposomes. Through a series of operations such as synthesis, purification, encapsulation, and labeling, the PA@TLipo have been prepared. Moreover, the cytotoxicity, bone targeting and anti-osteoporosis effect was verified by cell and animal experiments.Results: In the aspect of targeting, the PA@TLipo can effectively aggregate on the bone tissue to reduce bone loss, and in terms of toxicity, PA@TLipo could increase the bone target ability in comparison to nontargeted liposome, thereby mitigating systemic cytotoxicity. Moreover, PA@TLipo inhibited osteoclast formation and bone resorption in vitro and reduced bone loss in ovariectomy-induced osteoporotic mice.Conclusion: In this study, a novel therapeutic agent was designed and constructed to treat osteoporosis, consisting of a liposome material as the drug pocket, PA as the anti-osteoporosis drug, and ALN as the bone-targeting molecule. And our study is the first to employ a bone-targeted delivery system to deliver PA for OVX-induced bone loss, providing an innovative solution for treating osteoporosis.Keywords: bone targeting, alendronate functionalized liposome, pomolic acid, osteoporosis therapy

Qianqian Li,1,&ast; Yujie Liu,2,&ast; Zulun Zhang,1 Sheng Zhang,1 Xiao Ding,2 Faming Zhang1,3 1Department of Microbiota Medicine & Medical Center for Digestive Diseases, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, People’s Republic of China; 2Department of Medicine & Therapeutics, the Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 3National Clinical Research Center for Digestive Diseases, Xi’an, 710032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Faming Zhang, Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, 121 Jiangjiayuan, Nanjing, 210011, People’s Republic of China, Email fzhang@njmu.edu.cnPurpose: There is scarce evidence to support the effectiveness of faecal microbiota transplantation (FMT) in improving sleep among individuals with inflammatory bowel disease (IBD). Our study aimed to evaluate the effect of washed microbiota transplantation (WMT) (the new method of FMT) on the sleep of patients with IBD in short term.Patients and Methods: This prospective study was conducted as part of two interventional clinical trials (starting on February 2013 and expected to end on December 2025) and placed significant emphasis on evaluating sleep quality in patients with IBD. To measure subjective sleep, we used the Pittsburgh sleep quality index (PSQI). The primary endpoint was the PSQI score one month after WMT.Results: This stage study included 52 eligible patients evaluated by PSQI questionnaire who underwent WMT from January 2020 to March 2021 and 47 patients were enrolled for analysis. The age of the patients ranged from 13 to 60 years, with a mean of 33.4 years, and 57.4% (25/47) of the patients were male. The PSQI scores for all 47 patients one month after undergoing WMT were significantly lower (Cohen d = 0.59, p < 0.001) compared to the baseline. Moreover, baseline PSQI score was correlated with the difference value of the PSQI score before and after WMT (post-PSQI minus pre-PSQI) (r = 0.61, p < 0.05).Conclusion: The study suggests that WMT might be a helpful intervention for improving the sleep quality of patients with IBD, encouraging clinicians to consider its use in clinical practice for addressing poor sleep in IBD patients.Clinical Trial Registration: ClinicalTrials.gov; ID: NCT01793831, NCT01790061.Keywords: faecal microbiota transplantation, transendoscopic enteral tubing, sleep disorder, Crohn’s disease, ulcerative colitis, inflammatory bowel disease

Jiangpei Shi,1,&ast; Rongguang Zhang,1,&ast; Yu Wang,1 Yingwei Sun,1 Xiaoyan Gu,1 Yu An,1 Xinyu Chai,1 Xiaoyu Wang,2 Zhi Wang,1 Yaqi Lyu,1 Teng Guo,1 Nianping Feng,1 Ying Liu1 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nianping Feng; Ying Liu, Email npfeng@shutcm.edu.cn; debbyly@shutcm.edu.cnBackground: Metastasis is a complex process involving multiple factors and stages, in which tumor cells and the tumor microenvironment (TME) play significant roles. A combination of orally bioavailable therapeutic agents that target both tumor cells and TME is conducive to prevent or impede the progression of metastasis, especially when undetectable. However, sequentially overcoming intestinal barriers, ensuring biodistribution in tumors and metastatic tissues, and enhancing therapeutic effects required for efficient therapy remain challenging.Methods: Inspired by the unique chemical features of natural herbs, we propose an oral herb–nanoparticle hybrid system (HNS) formed through the self-binding of Platycodon grandiflorum–Curcuma zedoaria (HG), a herb pair/group used in clinical practice to treat breast cancer metastasis, to lipid–polymer nanoparticles (LPNs) loaded with silibinin. The molecular structure responsible for HG association with LPNs was assessed using surface-enhanced Raman spectroscopy for HNS surface chemistry characterization. Moreover, the molecular class of HG was identified using UPLC–Orbitrap–MS/MS to further confirm the surface binding. Mucus diffusion and in vivo biodistribution were evaluated using in vitro multiple-particle tracking and environment-responsive fluorescence probe in 4T1 tumor-bearing mice, respectively. The alleviation of breast cancer metastasis was assessed in 4T1 tumor-bearing mice, and the underlying mechanism was investigated.Results: The HNS reduced particle–mucus interactions by altering hydrophilicity and surface characteristics compared to LPNs. The epithelium transportation of HNS and absorption through Peyer’s patch in mice were improved, promoting their biodistribution in the lung and tumor tissues. Furthermore, the HNS alleviated lung metastasis by inducing cell apoptosis and regulating the expression of MMP-9 and TGF-β 1, which altered the TME in 4T1 tumor-bearing mice.Conclusion: HNS provides an appealing system with multi-component binding of herbal medicine to facilitate both oral nanoparticle delivery efficiency and the alleviation of lung metastasis. This strategy may potentially help improve treatment for patients with breast cancer.Keywords: herb–nanoparticle hybrid system, intestinal biological barrier, tumor microenvironment, breast cancer lung metastasis

Xinling Zhao,1,2,&ast; Huijin Jie,3,&ast; Jun Wang,1 Yu Liu,4 Yilin Liu,2 Fuyi Qin,2 Qing Long,2 Xi Hou,5 Xin-Wen Zhang,6 Wenzhi Wu,7 Xiaoqin Wu,2 Jing Li,8 Yong Zeng2 1Department of Clinical Psychology, People’s Hospital of Chongqing Liang Jiang New Area, Chongqing, People’s Republic of China; 2Department of Psychiatry, the Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Haining Fourth People’s Hospital, Haining, People’s Republic of China; 4Department of Psychiatry, the First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 5Department of Clinical Psychology, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi, People’s Republic of China; 6Department of Psychiatry, Hong He Second People’s Hospital, Jian Shui, People’s Republic of China; 7Faculty of psychology, Beijing Normal University, Beijing, People’s Republic of China; 8Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Li; Yong Zeng, Email lijingjingjing222@163.com; zengyong@kmmu.edu.cnBackground: Adolescents with major depressive (MDD) episodes associated with childhood trauma have a poorer response to treatment and a higher risk of suicide. The underlying etiology is unclear. Brain-derived neurotrophic factor (BDNF) could improve depressive symptoms by down-regulating mammalian target of rapamycin (mTOR) signaling pathways, which was involved in adverse environmental stimuli during neurodevelopment. BDNF and mTOR have not been reported simultaneously in adolescents with major depressive episodes associated with childhood trauma.Methods: Childhood Trauma Questionnaire-Short Form (CTQ-SF), Children’s Depression Inventory (CDI) and Children’s Depression Rating Scale-Revised (CDRS-R) were used to evaluate the recruited adolescents with major depression episodes. Serum BDNF and p-mTOR levels were measured by ELISA in 31 adolescents with major depression episodes with childhood trauma and 18 matched healthy control.Results: The serum levels of BDNF were significantly lower (p< 0.001); and the serum levels of p-mTOR were high (p=0.003) in the adolescents with the first episode of major depressive episode accompanied by childhood trauma. Of the 31 adolescents with major depressive episodes, 17 had suicide or self-injury. Compared with the healthy control group, the serum levels of BDNF in patients with suicide or self-injury were lower than those without suicide or self-injury(p< 0.001); the serum levels of p-mTOR were higher than those without suicide or self-injury (p=0.01). While in patients without suicide or self-injury, only serum p-mTOR was significantly higher than that in healthy group (p=0.028). BDNF was negatively correlated with CDRS-R (r=− 0.427, p=0.006), p-mTOR was positively correlated with CDI (r=0.364, p=0.048). According to Receiver Operating Characteristic Curve (ROC), the combination of serum BDNF and p-mTOR levels have better diagnostic value.Conclusion: Neurotrophic and signaling pathways, involving BDNF and p-mTOR, may play a role in adolescent MDD with a history of childhood trauma, especially patients with suicide and self-injury tendencies.Keywords: brain-derived neurotrophic factor, p-mTOR, major depressive disorder, suicide, adolescent, childhood trauma

Yongsheng Cao,1 Jianqin Zhao,2 Yanjuan Ma,2 Shujie Cao,2 Ying Liu2 1Department of Neurology, Sunshine Union Hospital, Weifang, Shandong, People’s Republic of China; 2Department of Endocrinology, Sunshine Union Hospital, Weifang, Shandong, People’s Republic of ChinaCorrespondence: Ying Liu, Department of Endocrinology, Sunshine Union Hospital, 9000 Yingqian Street, Weifang City, Shandong, 261000, People’s Republic of China, Email 175198989@qq.comBackground: Cardiovascular outcome trials indicate renal benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs); however, real-world efficacy and safety studies in Diabetic kidney disease (DKD) are scarce.Methods: This retrospective, single-arm real-world trial involved adults with DKD treated with GLP-1RA for at least 6 months. The primary endpoint was hemoglobin A1c (HbA1c) levels after 6 months.Results: This study included a total of 364 patients with DKD, 153 (42.0%) of whom were female. The median disease duration was 8.0 years, and the mean values of age, HbA1c level, body mass index, and the urinary albumin-to-creatinine ratio (UACR) were 52.1 years, 8.6%, 27.8 kg/m2, and 88.0 mg/g, respectively. Additionally, 73.6% and 26.4% of patients had mild and moderate DKD, respectively. Following 6 months of GLP-1RA treatment, the mean HbA1c level and UACR declined by 1.77% and 40.3%, respectively (both p < 0.001). Compared to their baseline values, patients exhibited significant improvements in 24-h urinary protein, estimated glomerular filtration rate (eGFR), fasting blood glucose, body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (all p < 0.001). Patients with a disease duration of < 10 years had more pronounced changes in the HbA1c level, UACR, and eGFR (all p < 0.001) than those with a disease duration of ≥ 10 years. Changes in SBP and DBP were more pronounced in patients also taking angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEis/ARBs) than in those not taking ACEis/ARBs, whereas the changes in UACR and eGFR did not significantly differ.Conclusion: Six-month GLP-1RA treatment improves glucose, blood pressure, lipids, and body weight in patients with mild-to-moderate DKD while slowing down kidney disease progression. It independently reduces proteinuria beyond ACEi/ARB impact, with early use yielding faster outcomes, supporting evidence-based practice.Keywords: diabetic kidney disease, type 2 diabetes, GLP-1RA, HbA1C, UACR

Longyi Zheng,1,&ast; Chengjing Zhang,2,&ast; Shichang Bu,1,&ast; Wencheng Guo,3,&ast; Tongtong Li,4 Ying Xu,5 Yunan Liu,4 Caimei Yuan,4 Chengwu Feng,4 Geng Zong,4 Jingwen Zhu,4 Maoying Xing,5 Xin Geng5 1Department of Endocrinology, Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Nutrition, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, People’s Republic of China; 3Department of General Surgery and Vascular Surgery, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 4CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China; 5National Center for Liver Cancer, Naval Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Maoying Xing; Xin Geng, Email xmyxing@sina.com; gxouc@hotmail.comBackground: Neuregulin 4 (NRG4) was known to be associated with serum lipid levels and atherosclerosis. However, it is unknown whether the role of NRG4 in lipid homeostasis is causal to atherosclerosis and whether the effect is beneficial across different atherosclerosis subtypes.Methods: We investigated the causal role of the levels of serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides regulated by NRG4 in subtypes of atherosclerosis through two sample Mendelian randomization. Aggregated genome-wide association study (GWAS) summary data for serum lipid level of 1.32 million individuals with European ancestry were obtained from the Global Lipids Genetics Consortium. GWAS summary data for four atherosclerosis subtypes (peripheral, coronary, cerebral and the other atherosclerosis) were obtained from FinnGen Consortium. Generalized inverse-variance–weighted Mendelian randomization and several sensitivity analyses were used to obtain the causal estimates.Results: A 1-SD genetically elevated LDL-C level mediated by NRG4 was validated to be nominally associated with the risk of peripheral atherosclerosis (log (odds ratio)= 4.14, 95% confidence interval 0.11 to 8.17, P = 0.04), and the other associations were not significant or could not be validated by sensitivity analyses.Conclusion: LDL-C lowering mediated by NRG4 is likely to prevent peripheral atherosclerosis.Keywords: Mendelian randomization analysis, NRG4, atherosclerosis, lipid

Wei Tang,1,2,&ast; Ying Liu,3,&ast; Xin Li,2 Guiyun Leng,2 Ju Gao,2 Yawu Wang,2 Jie Yao,2 Zhou Liu,2 Qiang Zhou,2 Yuanhong Xu1 1Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2Department of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of China; 3High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhong Xu, Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei, Anhui, 230022, People’s Republic of China, Tel +86 135 0569 4447, Fax +86 551 6292 2125, Email xyhong1964@ahmu.edu.cnPurpose: This study aimed to investigate the microbiological characteristics of clinically isolated Staphylococcus aureus with different hemolytic phenotypes in China.Materials and Methods: Using the three-point inoculation method, the hemolytic phenotypes of 1295 clinically isolated S. aureus strains were detected and categorized. Antimicrobial susceptibility testing of all strains was performed using a VITEK 2 Compact System. After sample size matching, plasma coagulase activity, catalase activity, mRNA expression of hemolysin genes (hla, hlb, hlc, and hld), biofilm formation, growth kinetics, inflammatory response of macrophages and cytotoxicity of S. aureus with different hemolytic phenotypes using the rabbit plasma kit, the catalase test on slides, qRT-PCR, crystal violet staining, the microcultivation assay, the ELISA kits, and the CCK-8 assay, respectively.Results: Seven categories of hemolytic phenotypes were identified. Accordingly, strains were categorized into seven different groups, including S. aureus with complete hemolytic phenotype (SCHP), S. aureus with weak hemolytic phenotype (SWHP), S. aureus with incomplete hemolytic phenotype 1 (SIHP-1), SIHP-2, SIHP-3, SIHP-4 and SIHP-5, the last three of which were reported for the first time. Except for the hemolytic phenotype, all seven groups differed in clinical isolation rates, antibiotic resistance profile, plasma coagulase activity, mRNA expression of hemolysin genes, biofilm formation, growth kinetics, inflammatory response of macrophages, and cytotoxicity.Conclusion: S. aureus with different hemolytic phenotypes have distinctive microbiological characteristics. Clinical microbiologists need to be vigilant about the hemolytic phenotypes when culturing S. aureus strains, and actively enhance communication with clinicians to optimize the treatment of infection.Keywords: Staphylococcus aureus, hemolytic phenotype, hemolysin, microbiological characteristics, antibiotic resistance

Kang Zhao,1,&ast; Rui Mao,2,&ast; Wei Yi,3– 6 Zhengyun Ren,3– 6 Yanjun Liu,3– 5 Huawu Yang,3– 5 Senlin Wang,3– 6 Zhonghui Feng4– 6 1Section for Day Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiao Tong University, Chengdu, 610031, People’s Republic of China; 2Department of Dermatology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3College of Medicine, Southwest Jiaotong University, Chengdu, People’s Republic of China; 4Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiao Tong University, Chengdu, Sichuan, People’s Republic of China; 5The Center for Obesity and Metabolic Health, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiao Tong University, Chengdu, 610031, People’s Republic of China; 6Medical Research Center, The Third People’s Hospital of Chengdu, The Affiliated Hospital of Southwest Jiao Tong University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhonghui Feng, Center of Gastrointestinal and Minimally Invasive Surgery, Department of General Surgery, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, 610031, People’s Republic of China, Email fengzh.2008@tsinghua.org.cnAim/Introduction: Type 2 diabetes mellitus (T2DM) is one of the most frequent and widespread disease in the world.Obesity is the most significant predictor of T2DM, but the exact mechanism how obesity promotes T2DM remains unknown. Finding specific biomarkers to assist in diagnosing and treating patients with obese and T2DM is critical.Materials and Methods: We collected liver tissues from obesity patients with and without T2DM for proteomic sequencing and immunohistochemistry assay. Analysis Gene Ontology(GO) enrichment, Kyoto Encyclopedia of Genes and Genomes(KEGG), and protein interaction network (PPI) were performed on the parameters and data derived from the Tandem Mass Tags(TMT)-based proteomics analysis of liver tissues. Transcriptome data were downloaded from the Gene Expression Omnibus(GEO)website and genes that are deferentially expressed in both transcriptome and proteome were selected.Results: We identified 140 deferentially expressed proteins from proteomic sequencing. Six biomarkers were deferentially expressed in both proteome and transcriptome with consistent changes in direction. The protein–protein interaction (PPI) analysis suggested CMPK1, the expression with greatest difference, was the core protein among the six biomarkers. Immunohistochemistry validated CMPK1 was upregulated significantly in the liver tissues of T2DM patients. The correlation analysis revealed that the expression of CMPK1 was significantly associated with key molecules in T2DM-related pathways at both protein and transcriptome levels.Conclusion and Novelty: Our study showed CMPK1 was upregulated in the liver of T2DM patients and provides a possible new target for screening and diagnosing T2DM in patients with obese and a novel theoretical basis for the pathophysiological mechanism of obesity-related metabolic diseases.Keywords: type 2 diabetes mellitus, obesity, CMPK1, proteomic, transcriptomic, immunohistochemistry

Jie Yu,1 Yanping Liu,2 Lingling Xu1 1Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Clinical Nutrition, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Yanping Liu; Lingling Xu, Email liuyp1227@vip.sina.com; llxuwsh@163.comBackground: The relationship between vitamin A levels and gestational diabetes mellitus (GDM) is not well understood, and prospective studies are lacking.Methods: This was a prospective, longitudinal study. A total of 391 women in early pregnancy were recruited between October and December 2018 at Shunyi District Maternal and Child Health Hospital (Beijing, China). Serum vitamin A concentration was measured at enrollment. GDM was diagnosed on the basis of a 75 g oral glucose-tolerance test at 24– 28 weeks of follow-up. Logistic regression was used for the analysis.Results: None of the subjects in the cohort had vitamin A deficiency or excess. At the follow-up, 76 participants had developed GDM. Participants who developed GDM were older and had higher body mass index, fasting insulin, HbA1c, fasting glucose, homeostasis model assessment for insulin resistance, triglyceride, low-density lipoprotein cholesterol, and high-sensitivity CRP levels, as well as higher serum vitamin A levels at baseline. On logistic multivariate analysis, higher vitamin A was positively associated with higher risk of GDM. The adjusted OR was 2.85 (95% CI 1.04– 7.80, P=0.042) for Q4 versus Q1 and 1.59 (95% CI 1.11– 2.28, P=0.011) for every 1 SD increase in serum vitamin A levels. In participants within the vitamin A reference range (0.33– 0.78 mg/L), the positive association also maintained significance.Conclusion: Higher serum vitamin A levels were associated with higher GDM risks, even within the reference range. The results and possible mechanisms need to be further verified and clarified.Keywords: gestational diabetes mellitus, vitamin A, insulin resistance, inflammation

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

Hui Sun,&ast; Yan Liu,&ast; Ling Wang, Xiaoling Liu, WenHui Wang Department of Tuberculosis, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Wang; Xiaoling Liu, Department of Tuberculosis, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, No. 1-1 Zhongfu Road, Nanjing, Jiangsu Province, 210000, People’s Republic of China, Tel +86 83626512, Email liuxiaoling15l@163.comObjective: Accurate diagnosis is very important to block the transmission of tuberculosis. The quality of sputum culture affects the diagnostic accuracy. The quality of sputum samples is not optimistic. Therefore, this study investigated whether health care failure mode and effect analysis (HFMEA) can improve specimen quality and detection efficiency in sputum specimen management in tuberculosis departments.Methods: This study is a non-randomized controlled trial study. A convenience sampling method was used to select 110 patients who visited the Department of Tuberculosis of the Second Hospital of Nanjing from September to November 2022 and December 2022 to February 2023 as the control group and the experimental group. Control groups followed standard operating procedures for sputum specimen collection. In the experimental group, HFMEA model was used to control the quality on this basis. After 3 months of intervention, the qualified rate and positive detection rate of sputum samples were compared between the two groups.Results: A total of 634 sputum specimens were included in the experimental group and 647 in the control group. Compared with the control group, the qualification rate of sputum specimens was higher in the experimental group (84.54% vs 79.13%); the positive detection rates of the X-Pert assay (27.88% vs 16.19%), sputum culture (20.29% vs 12.68%), and sputum smear (22.29% vs 15.81%) were all higher in the experimental group (all P < 0.05). Patients in the experimental group had higher knowledge mastery and nurse sputum sample management scores (P < 0.05). However, patient satisfaction with sputum specimen management in the experimental group was lower than in the control group (7.72 ± 0.74 vs 8.38 ± 0.85, P < 0.001).Conclusion: The application of the HFMEA model in sputum specimen management can effectively improve specimen quality and positive detection rates.Keywords: healthcare failure mode and effect analysis (HFMEA), tuberculosis, sputum, nursing care, risk management

Bo Jin,1 Kexin Lu,2 Wenna Gao,1 Yixian Liu,3 Mengfei Wang,2 Xiaojun Zhang,3 Huiping Chen,3 Liyun Zheng,3 Min Zou3 1Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Hennan, 450052, People’s Republic of China; 2BGI College, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 3Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450052, People’s Republic of ChinaCorrespondence: Min Zou; Liyun Zheng, Email Minzou1980@126.com; zhengliyun@zzu.edu.cnBackground: At present, the few photothermal/chemotherapy studies about retinoblastoma that have been reported are mainly restricted to ectopic models involving subcutaneous implantation. However, eyeball is unique physiological structure, the blood-retina barrier (BRB) hinders the absorption of drug molecules through the systemic route. Moreover, the abundant blood circulation in the fundus accelerates drug metabolism. To uphold the required drug concentration, patients must undergo frequent chemotherapy sessions.Purpose: To address these challenges above, we need to develop a secure and effective drug delivery system (FA-PEG-PDA-DOX) for the fundus.Methods: We offered superior therapeutic efficacy with minimal or no side effects and successfully established orthotopic mouse models. We evaluated cellular uptake performance and targeting efficiency of FA-PEG-PDA-DOX nanosystem and assessed its synergistic antitumor effects in vitro and vivo. Biodistribution assessments were performed to determine the retention time and targeting efficiency of the NPs in vivo. Additionally, safety assessments were conducted.Results: Cell endocytosis rates of the FA-PEG-PDA-DOX+Laser group became 5.23 times that of the DOX group and 2.28 times that of FA-PEG-PDA-DOX group without irradiation. The fluorescence signal of FA-PEG-PDA-DOX persisted for more than 120 hours at the tumor site. The number of tumor cells (17.2%) in the proliferative cycle decreased by 61.6% in the photothermal-chemotherapy group, in contrast to that of the saline control group (78.8%). FA-PEG-PDA-DOX nanoparticles(NPs) exhibited favorable biosafety and high biocompatibility.Conclusion: The dual functional targeted nanosystem, with the effects of DOX and mild-temperature elevation by irradiation, resulted in precise chemo/photothermal therapy in nude mice model.Keywords: retinoblastoma, orthotopic model, nanoparticle, synergistic therapy