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Changhong Xu,1,* Yun Deng,1,* Xinyi Gong,2,* Huabin Wang,1 Jiangwei Man,1 Hailong Wang,1 Kun Cheng,1 Huiming Gui,1 Shengjun Fu,1 Shenghu Wei,3 Xiaoling Zheng,4 Tuanjie Che,4 Liyun Ding,3 Li Yang1 1Department of Urology, Institute of Urology, Gansu Province Clinical Research Center for Urinary System Disease, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, People’s Republic of China; 2The Second Clinical Medical College of Lanzhou University, Lanzhou, Gansu, 730030, People’s Republic of China; 3School of Physical Science and Technology, Lanzhou University, Lanzhou, 730000, People’s Republic of China; 4Innovation Center of Functional Genomics and Molecular Diagnostics Technology of Gansu Province, Lanzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Yang; Liyun Ding, Email ery_yangli@lzu.edu.cn; dingly@lzu.edu.cnBackground: Renal ischemia-reperfusion injury (RIRI) is a significant cause of acute kidney injury, complicating clinical interventions such as kidney transplants and partial nephrectomy. Recent research has indicated the role of cuproptosis, a copper-dependent cell death pathway, in various pathologies, but its specific involvement in RIRI remains insufficiently understood. This study aims to investigate the role of cuproptosis-related genes in RIRI and establish robust diagnostic models.Methods: We analyzed transcriptomic data from 203 RIRI and 188 control samples using bioinformatics tools to identify cuproptosis-related differentially expressed genes (CRDEGs). The relationship between CRDEGs and immune cells was explored using immune infiltration analysis and correlation analysis. Gene Set Enrichment Analysis (GSEA) was conducted to identify pathways associated with CRDEGs. Machine learning models, including Least Absolute Shrinkage and Selection Operator(LASSO) logistic regression, Support Vector Machine Recursive Feature Elimination (SVM-RFE), Clustering analysis, and weighted gene co-expression network analysis (WGCNA), were used to construct diagnostic gene models. The models were validated using independent datasets. Experimental validation was conducted in vivo using a mouse bilateral RIRI model and in vitro using an HK-2 cell hypoxia-reoxygenation (HR) model with copper chelation intervention. HE, PAS, and TUNEL staining, along with plasma creatinine and blood urea nitrogen (BUN) measurements, were used to evaluate the protective effect of the copper chelator D-Penicillamine (D-PCA) on RIRI in mice. JC-1 and TUNEL staining were employed to assess apoptosis in HK-2 cells under hypoxia-reoxygenation conditions. Immunofluorescence and Western blot (WB) techniques were used to verify the expression levels of the SDHB and NDUFB6 genes.Results: A total of 18 CRDEGs were identified, many of which were significantly correlated with immune cell infiltration. GSEA revealed that these genes were involved in pathways related to oxidative phosphorylation and immune response regulation. Four key cuproptosis marker genes (LIPA, LIPT1, SDHB, and NDUFB6) were incorporated into a Cuproptosis Marker Gene Model(CMGM), achieving an area under the curve (AUC) of 0.741– 0.834 in validation datasets. In addition, a five-hub-gene SVM model (MOAP1, PPP2CA, SYL2, ZZZ3, and SFRS2) was developed, demonstrating promising diagnostic performance. Clustering analysis revealed two RIRI subtypes (C1 and C2) with distinct molecular profiles and pathway activities, particularly in oxidative phosphorylation and immune responses. Experimental results showed that copper chelation alleviated renal damage and cuproptosis in both in vivo and in vitro models.Conclusion: Our study reveals that cuproptosis-related genes are significantly involved in RIRI, particularly influencing mitochondrial dysfunction and immune responses. The diagnostic models developed showed promising predictive performance across independent datasets. Copper chelation demonstrated potential therapeutic effects, suggesting that cuproptosis regulation may be a viable therapeutic strategy for RIRI. This work provides a foundation for further exploration of copper metabolism in renal injury contexts.Keywords: cuproptosis, renal ischemia-reperfusion injury, RIRI, gene diagnostic models, copper chelators, bioinformatics analysis

Shiya Zeng,1,* Yanyue Tan,1,2,* Zhiwei Cao,3 Yunhao Zheng,1 Tiqian Liu,1 Yifei Deng,1 Xin Xiong1 1State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Nursing, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3School of Stomatology, Tianjin Medical University, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Xiong, State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, No. 15, West Section 3, Second Ring Road, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86 028 85501425, Email drxiongxin@scu.edu.cnObjective: Growing researches explore vitamin D’s role in temporomandibular disorders (TMDs), but the link between vitamin D and TMDs remains debated. To clarify the causal relationship, we conducted a Mendelian randomization (MR) analysis using data from genome-wide association studies (GWAS).Subjects and Methods: The GWAS dataset of vitamin D (GWAS ID: ukb-d-30890_irnt; sample size: 329247) was obtained from the IEU Open GWAS project. And that of TMDs (GWAS ID: finn-b-TEMPORO; sample size: 134280), initiated on August 25th, 2017 and publicly released on December 18th, 2023, was extracted from the FinnGen dataset, whose cases were diagnosed based on the revised International Classification of Diseases, 10th Edition (ICD-10) code K07.6. Both datasets were obtained from the European population. According to three assumptions of MR analysis, a bi-directional MR analysis was performed to measure the causal relationship, with Inverse variance weighted (IVW) as the primary method and MR Egger and Weighted median as supplement. Moreover, diverse sensitivity analyses, including Cochran’s Q test, MR Egger intercept, Mendelian randomized polymorphism RESidual Sum and Outlier (MR-PRESSO), and leave-one-out analysis, were used to verify the stability of the findings.Results: The MR analysis supported causal effects of vitamin D levels on TMDs risks within the European population using IVW method [odds ratio = 1.316; 95% confidence interval = 1.086 to 1.595; P = 0.005], supported by MR Egger and Weighted median. While there was no indication that TMDs have a direct impact on vitamin D levels [β: − 0.00738, standard error = 0.00665; P = 0.568].Conclusion: The study revealed that within the European population higher levels of vitamin D led to higher risks of developing temporomandibular disorders, but found no obvious evidence that TMDs are causally associated with vitamin D. The conclusion should be cautiously interpreted, given the selection bias of TMDs patients sample.Keywords: Mendelian randomization analysis, temporomandibular joint disorders, vitamin D, 25-hydroxyvitamin D

Yang Deng,1,* Rui Duan,2,* Ye Hong,2,* Qiang Peng,2 Zhong-Yuan Li,2 Xiang-Liang Chen,2 Ying-Dong Zhang1 1Department of Neurology, Nanjing First Hospital, China Pharmaceutical University, Nanjing, 210006, People’s Republic of China; 2Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiang-Liang Chen, Department of Neurology, Nanjing First Hospital, Nanjing Medical University, No. 68, Changle Road, Nanjing, Jiangsu, 210006, People’s Republic of China, Email chenxl@njmu.edu.cn Ying-Dong Zhang, Department of Neurology, Nanjing First Hospital, China Pharmaceutical University, No.68, Changle Road, Nanjing, Jiangsu, 210006, People’s Republic of China, Email zhangyingdong@njmu.edu.cnPurpose: Vascular dementia (VaD) is the second most common dementia in the world. An increasing number of studies have demonstrated the important role of long non-coding RNAs (lncRNAs) in VaD. Our previous investigation demonstrated that Trimethylamine-N-oxide (TMAO) exacerbates cognitive impairment and neuropathological alterations in VaD rats. Thus, we hypothesized that TMAO could play an injury role in VaD by regulating lncRNAs.Materials and Methods: The rats using the bilateral common carotid artery (2VO) model were administered TMAO (120 mg/kg) for 8 consecutive weeks, 4 weeks preoperatively and 4 weeks postoperatively. High-throughput sequencing was conducted to investigate the effects of TMAO treatment on lncRNA expression in rat hippocampus and bioinformatics analysis was performed to identify potential downstream targets. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the levels of lncRNA fetal-lethal noncoding developmental regulatory RNA (Fendrr), miR-145-5p, and paxillin (PXN). Learning and spatial memory capacities were measured, as well as inflammatory factors. Nissl staining was used to observe neuronal injury in the CA1 area of the hippocampus. Furthermore, we used the Fendrr loss-of-function assay, miR-145-5p gain-of-function assays and PXN loss-of-function assay to explore the mechanisms by which TMAO acts on VaD.Results: TMAO administration upregulated lncRNA Fendrr expression in the rat hippocampus, while the damaging effects of TMAO were counteracted after knockdown of Fendrr. Fendrr exhibits highly expressed in 2VO rats and sponged miR-145-5p, which targets PXN. Silencing of Fendrr or PXN, or promotion of miR-145-5p improved neurological function injury, reduced neuronal damage, as well as repressed inflammation response. Inhibition of miR-145-5p abrogated up Fendrr knockdown mediated influence on 2VO rats.Conclusion: The results of this study indicated that TMAO inhibits the miR-145-5p/PXN axis by increasing the Fendrr expression, thus exacerbating the development of VaD.Keywords: trimethylamine N-oxide, neuroinflammation, Fendrr, MiR-145-5p, PXN, vascular dementia

Changhong Xu,1,&ast; Yun Deng,1,&ast; Jiangwei Man,1,&ast; Huabin Wang,1 Tuanjie Che,2 Liyun Ding,3 Li Yang1 1Department of Urology, Institute of Urology, Gansu Province Clinical Research Center for Urinary System Disease, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, People’s Republic of China; 2Innovation Center of Functional Genomics and Molecular Diagnostics Technology of Gansu Province, Lanzhou, People’s Republic of China; 3School of Physical Science and Technology, Lanzhou University, Lanzhou, 730000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Yang, Department of Urology, Institute of Urology, Gansu Province Clinical Research Center for Urinary System Disease, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, People’s Republic of China, Email ery_yangli@lzu.edu.cnObjective: This study investigates the targets, pathways, and mechanisms of Schisandrin B (Sch B) in alleviating renal ischemia-reperfusion injury (RIRI) using RNA sequencing and network pharmacology.Methods: The effects of Sch B on RIRI were assessed using hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining, along with measurements of blood creatinine and urea nitrogen (BUN). Differential gene expression in mouse models treated with RIRI and Sch B+RIRI was analyzed through RNA-Seq. Key processes, targets, and pathways were examined using network pharmacology techniques. The antioxidant capacity of Sch B was evaluated using assays for reactive oxygen species (ROS), mitochondrial superoxide, and JC-1 membrane potential. Molecular docking was employed to verify the interactions between key targets and Sch B, and the expression of these targets and pathway was confirmed using qRT-PCR, Western blot, and immunofluorescence.Results: Sch B pre-treatment significantly reduced renal pathological damage, inflammatory response, and apoptosis in a mouse RIRI model. Pathological damage scores dropped from 4.33 ± 0.33 in the I/R group to 2.17 ± 0.17 and 1.5 ± 0.22 in Sch B-treated groups (p < 0.01). Creatinine and BUN levels were also reduced (from 144.6 ± 21.05 μmol/L and 53.51 ± 2.34 mg/dL to 50.44 ± 5.61 μmol/L and 17.18 ± 0.96 mg/dL, p < 0.05). Transcriptomic analysis identified four key targets (AKT1, ALB, ACE, CCL5) and the PI3K/AKT pathway. Experimental validation confirmed Sch B modulated these targets, reducing apoptosis and oxidative stress, and enhancing renal recovery.Conclusion: Sch B reduces oxidative stress, inflammation, and apoptosis by modulating key targets such as AKT1, ALB, ACE, and CCL5, while activating the PI3K/AKT pathway, leading to improved renal recovery in RIRI.Keywords: renal ischemia-reperfusion injury, schisandrin B, transcriptomics, network pharmacology, PI3K/AKT pathway

Hao Huang,1 Zhiping Long,2 Ying Deng,3 Zhicong Huang,3 Zhonghua Lv,4 Qian Sun,4 Hui Liu,4 Hongsheng Liang,5 Fulan Hu6 1Department of Preventive Medicine, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong, People’s Republic of China; 2Department of Epidemiology, Public Health School of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 3Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Neurosurgery, Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 5Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 6Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Medical School, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Fulan Hu, Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Medical School, Shenzhen, Guangdong, People’s Republic of China, Email hufu1525@163.com Hao Huang, Department of Preventive Medicine, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong, People’s Republic of China, Email hhxiaowo@163.comPurpose: Mitochondrial metabolism is essential for energy production and the survival of brain cells, particularly in astrocytes. Cuproptosis is a newly identified form of programmed cell death that occurs due to the disruption of mitochondrial metabolism caused by excessive copper toxicity. However, the relationship between cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) and the prognosis of gliomas remains unclear.Patients and Methods: In this study, we utilized 32,293 cells obtained from three in-house single-cell RNA sequencing (scRNA-seq) datasets, along with 6,148 cells acquired from the Chinese Glioma Genome Atlas (CGGA) involving 14 glioma patients, to identify and validate the TME of gliomas.Results: Based on an analysis of 32,293 single cells, we investigated intra-tumor heterogeneity, intercellular communication, and astrocyte differentiation trajectories in gliomas. Our findings revealed that the TGFβ signaling pathway exhibited a higher relative strength in astrocyte subpopulations. Additionally, we identified a novel three-gene signature (CDKN2A, SOX2, and MPC1) was identified for prognostic prediction. Furthermore, glioma patients with a high-risk score demonstrated poorer overall survival (OS) compared to those with a low-risk score in both training and testing datasets (Ptraining set < 0.001; Ptest set = 0.037).Conclusion: Our study revealed the prognostic value of the CRGs in astrocytes exhibiting tumor immunosuppressive characteristics in glioma. We established a novel three-gene prognostic model that offers new insights into the prognosis and treatment strategies for gliomas. Keywords: scRNA-seq, gliomas, astrocyte, cuproptosis, prognosis

Ning Rong,1 Zhi-Wei Li,1 Jian Yuan,2 Ze-Min Shao,2 Yun Deng,2 De-Sheng Zhu,2,3 Zhong-Wu Sun1 1Department of Neurology, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2Department of Neurology, Baoshan Branch, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200444, People’s Republic of China; 3Department of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of ChinaCorrespondence: Zhong-Wu Sun, Department of Neurology, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China, Tel +86-13805515857, Email sunzhwu@126.com De-Sheng Zhu, Department of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, No. 160, Pujian Road, Shanghai, 200127, People’s Republic of China, Tel +86-13564719779, Email deshengzhu2008@sina.comObjective: Fasting blood glucose (FBG) is a recognized risk factor for Ischemic Stroke, but little research has examined the interaction among FBG, Platelet Distribution Width (PDW) and the severity of neuronal damage. Thus, the present study constructs a moderated mediation model aimed to elucidate the relationships among FBG, PDW, and NIHSS scores in patients with acute ischemic stroke (AIS).Methods: We conducted a cross-sectional study on 431 AIS patients. Upon hospital admission, we assessed the patients’ NIHSS scores and collected blood samples to measure FBG and PDW levels. The relationship between FBG and NIHSS scores moderated by PDW was analyzed by linear curve fitting analysis, multiple linear regression analysis, and moderated mediation analysis respectively.Results: In the tertile grouping based on FBG, both PDW and NIHSS scores of AIS patients demonstrated an increase corresponding with rising levels of FBG (p< 0.001 for both). Multiple linear regression analysis revealed that, the β coefficients (95% CI) for the relationship between FBG and NIHSS scores were 1.49 (1.27– 1.71, p< 0.01) post-adjustment for potential confounders. The β coefficients (95% CI) for the relationship between FBG and PDW were 0.02 (0.01– 0.04, p< 0.01) post-adjustment. Likewise, for the relationship between PDW and NIHSS scores, the β coefficients (95% CI) were 4.33 (3.07– 5.59, p< 0.01) after adjustment. These positive association remained consistent in sensitivity analysis and hierarchical analysis. Smoothed plots suggested that there are linear relationships between FBG and PDW and NIHSS scores respectively. Further mediation analysis indicated that increased PDW significantly (p< 0.01) mediated 5.91% of FBG-associated increased NIHSS scores.Conclusion: This study suggested that FBG levels were associated with NIHSS scores, and the FBG-associated neurological impairment may be partially mediated by PDW. These findings underscore the importance of monitoring FBG and PDW levels in AIS patients, potentially guiding risk intervention strategies.Keywords: acute ischemic stroke, fasting blood glucose, platelet distribution width, multivariate analysis, mediation analysis

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

Jianming Yang,1,&ast; Yu Zhang,2,&ast; Yewu Chen,1,&ast; Yang Yang,1,3 Yinan Deng1 1Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Breast Surgery, Sun Yat-sen Memorial Hospital, Guangzhou, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Yang; Yinan Deng, Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, People’s Republic of China, Tel +86 20 85253106, Fax +86 20 85252276, Email yysysu@163.com; dengyinan2010@163.comBackgrounds and Aims: Multiple regimens of immune checkpoint inhibitors (ICIs) plus targeted therapies are commonly prescribed as first-line treatments for unresectable hepatocellular carcinoma (uHCC). Here, we aimed to investigate the correlation between dynamic changes of neutrophil-to-lymphocyte ratio (NLR) and tumor response to the combination of ICIs and targeted therapies for uHCC.Methods: Sixty-one patients who received ICIs plus targeted therapies for uHCC were enrolled in this retrospective study. The NLR before and at 3– 6 weeks after treatments were assessed to calculate the dynamic NLR changes (ΔNLR). Multivariate logistic regression and Cox regression models were used to explore the relationship between dynamic NLR changes and tumor response or progression-free survival (PFS), respectively. Furthermore, we assessed the predictive effect of alpha-fetoprotein (AFP) changes in combination with dynamic NLR changes compared to AFP changes alone.Results: The NLR at 3– 6 weeks and ΔNLR after treatments significantly increased in patients who underwent progressive disease (PD), while the baseline NLR showed no significant difference between different tumor responses. Increased NLR and AFP after treatments were both independent predictors of PD (For NLR increase: OR, 2.28; 95% CI, 1.47– 3.88, P < 0.001; For AFP increase: OR, 1.46; 95% CI, 1.03– 2.17, P = 0.043), and correlated with worse PFS (for NLR increase: HR, 4.08; 95% CI, 1.99– 8.36, P < 0.001; for AFP increase: HR, 2.10; 95% CI, 1.04– 4.24, P = 0.039). The receiver operating characteristic (ROC) curve and net reclassification index (NRI) showed that the combination of dynamic NLR and AFP changes was better than AFP changes alone on predicting PD (AUC: 0.83 vs 0.68, P = 0.034; NRI: 0.340, P = 0.048) and PFS (AUC: 0.80 vs 0.70, P = 0.166; NRI: 0.431, P = 0.042).Conclusion: Dynamic changes of NLR might be an effective predictor of the therapeutic response to ICIs plus targeted therapies for uHCC.Keywords: hepatocellular carcinoma, neutrophil-to-lymphocyte ratio, immune checkpoint inhibitors, targeted therapies

Cai-Dong Liu,1,2,&ast; Qiang Peng,3,&ast; Shi-Yao Wang,3,&ast; Yang Deng,2 Zhong-Yuan Li,3 Zhao-Han Xu,3 Liang Wu,3 Ying-Dong Zhang,2,3 Rui Duan3 1Department of Laboratory Medicine, Nanjing First Hospital, China Pharmaceutical University, Nanjing, Jiangsu, 210006, People’s Republic of China; 2School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, 210006, People’s Republic of China; 3Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, 210006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying-Dong Zhang; Rui Duan, Department of Neurology, Nanjing First Hospital, Nanjing Medical University, No. 68, Changle Road, Nanjing, Jiangsu, People’s Republic of China, Email zhangyingdong@njmu.edu.cn; duanruicpu@163.comPurpose: Acute ischemic stroke (AIS) has seriously threatened people’s health worldwide and there is an urge need for early diagnosis and effective treatment of AIS. This research intended to clarify the regulatory role of circ_0008146/miR-342-5p/ACSL4 axis in AIS.Methods: High-throughput small RNA sequencing analysis was adapted to identify differentially expressed miRNAs between the AIS and control group. The circ_0008146, miR-342-5p, and ACSL4 levels were detected by qRT-PCR. Middle cerebral artery occlusion/reperfusion (MCAO/R) models were constructed in C57BL/6J mice. Assay kits were used to determine Fe2+ levels and a battery of oxidative stress and lipid peroxidation indicators, including ROS, MDA, LPO, SOD and GSH/GSSG ratio. The protein levels of ACSL4 were measured by Western blot. The behavioral function was assessed using neurobehavioral tests. TTC staining was employed to visualize infarction size. Nissl staining was adapted to detect histopathological changes. Receiver operating characteristic curve and correlation analysis were applied to investigate the clinical value and association of miR-342-5p and ACSL4.Results: A total of 44 AIS patients and 49 healthy controls were enrolled in our study. The small RNA sequencing unveiled a significant decrease in miR-342-5p levels in AIS patients. MiR-342-5p inhibited oxidative stress and RSL3-induced ferroptosis after cerebral ischemic/reperfusion injury in vivo by targeting ferroptosis-related gene ACSL4. Circ_0008146 acted as a sponge of miR-342-5p, and overexpression of circ_0008146 increased neurological deficits and brain injury in mice. Circ_0008146 contributed to ferroptosis in cerebral infarction via sponging miR-342-5p to regulate ACSL4. Plasma miR-342-5p and ACSL4 demonstrated significant correlation and good diagnostic value for AIS patients.Conclusion: This study provides the first in vivo evidence to show that circ_0008146 exacerbates neuronal ferroptosis after AIS via the miR-342-5p/ACSL4 axis. Furthermore, miR-342-5p/ACSL4 axis holds promise as a viable therapeutic target and practical biomarkers for AIS patients.Keywords: ischemic stroke, miRNA, circRNA, ferroptosis, biomarker

Lei Liu,1,&ast; Shanshan Liu,2,&ast; Fuyan Bai,1 Yangxin Deng,1 Xinhuan Zhang,1 Li Wang3 1Department of Endocrinology, the Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, People’s Republic of China; 2General Gynecology, the Tai ‘an Central Hospital, Taian, Shandong, People’s Republic of China; 3Department of Pharmacy, the Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinhuan Zhang; Li Wang, Email zhangxh22009@126.com; suxinlan1027@126.comBackground: An important factor in the pathogenesis of polycystic ovary syndrome (PCOS) is chronic low-grade inflammation. However, the exact pathophysiology of PCOS is currently unknown, which makes clinical diagnosis and the development of effective treatments more difficult. We aimed to investigate the role of the inflammatory response in initiating and progressing PCOS.Methods: 13 control granulosa cell samples and 15 granulosa cell samples from patients with PCOS were obtained from the GSE102293, GSE34526, and GSE5850 datasets. The gene set variation analysis (GSVA) method was used to calculate the inflammatory response score. Subsequently, the genes associated with inflammation in the hub were identified using differential expression analysis and weighted gene co-expression network analysis (WGCNA). The findings were confirmed by analysis of independent datasets and examination of clinical samples by qRT-PCR analysis. A consensus cluster analysis was conducted to categorize the PCOS samples into subtypes related to inflammation. Functional enrichment and analysis of immune cell infiltration were conducted to explore the potential mechanisms involved. Additionally, the CMap database was utilized to predict potential drugs, and the results were confirmed through molecular docking.Results: During the training cohort analysis, we identified five distinct genes (TGFBR2, ICAM3, WIPF1, SLC11A1, and NCF2) that could serve as potential diagnostic markers for PCOS. The expression levels of these genes were confirmed through validation in both the test set and clinical samples. In training cohort, two distinct inflammatory patterns (C1 and C2) were identified, and the C2 subtype exhibited activated immune- and inflammation-related pathways. Esmolol was shown to have potential as a drug to treat PCOS and it showed good results for molecular binding at TGFBR2, ICAM3, WIPF1, SLC11A1, and NCF2 proteins.Conclusion: Five diagnostic biomarkers and two inflammation-related molecular types associated with PCOS were identified, and esmolol was a potential drug for PCOS treatment. Our findings provided new diagnostic markers and potential small-molecule drugs for PCOS diagnosis and prevention.Keywords: polycystic ovary syndrome, inflammatory response, diagnostic biomarkers, molecular subtypes, esmolol

Xiamin Pu,1 Houqiang Huang,2 Xiaolei Zhao,3 Feng Liu,1 Yebo Leng,4 Ya Deng,5 Lingyi Huang,5 Xingchen Zhou,5 Fen Xu,1 Yongli Huang,6 Shengmin Guo2 1Department of Cardiovascular Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Nursing, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Department of Hematology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 4Department of Orthopedics, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 5School of Nursing, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 6Department of Outpatient, The Affiliated Hospital, Southwest Medical University, Luzhou, People’s Republic of ChinaCorrespondence: Shengmin Guo, Department of Nursing, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel +86-13980255653, Email 2930773281@qq.comBackground: A global public health problem, frailty is closely associated with poor prognosis after percutaneous coronary intervention (PCI) in older patients with acute myocardial infarction (AMI). Although exercise intervention is the most commonly used method to reverse and alleviate frailty, its application is restricted in patients with acute myocardial infarction following PCI due to cardiovascular instability and autonomic imbalance. Consequently, there is a need for a new practical intervention to address frailty syndrome in these patients.Purpose: This study aimed to investigate the effect of neuromuscular electrical stimulation in frail older AMI patients post-PCI.Patients and Methods: A single-blind, randomized controlled trial was carried out in the Department of Cardiovascular Medicine from March to October 2023. A total of 100 eligible participants were randomly divided into two groups: experimental (n = 50) and control (n = 50) groups, respectively. Both groups received usual care. The experimental group underwent neuromuscular electrical stimulation (NMES) on bilateral quadriceps and gastrocnemius muscles for 30 minutes daily from day 1 to day 7 after surgery. The primary outcomes measured included the frailty score, lower limb muscle strength, and lower limb muscle quality. Secondary outcomes included the activities of daily living score, inflammatory markers, and length of hospital stay. All participants were included in an intention-to-treat analysis after the study ended.Results: The frailty scores of the two groups exhibited a gradual decrease over time, and the scores of the experimental group were lower than those of the control group at 4 and 7 days after surgery (P< 0.001). Concurrently, the lower limb muscle strength showed an increasing trend over the time in the experimental group and a decreasing trend in the control group, and the scores of the experimental group surpassed those of the control group (p< 0.001). Moreover, a statistical difference was observed in the lower limb muscle mass across the groups after 7 days postoperatively compared with baseline on both sides (p< 0.05).Conclusion: Neuromuscular electrical stimulation has the potential to enhance lower limb function and alleviate frailty in elderly patients with acute myocardial infarction after PCI. These findings introduce a novel intervention approach for frailty management in the elderly population.Keywords: acute myocardial infarction, older, frailty, neuromuscular electrical stimulation, PCI

Jingzhan Huang,1,&ast; Jialong Liu,1,&ast; Jin Lan,1,&ast; Jingbo Sun,1 Kun Zhou,1 Yunyao Deng,1 Li Liang,2 Lixin Liu,1,&ast; Xiaolong Liu1 1Department of General Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lixin Liu; Xiaolong Liu, Department of General Surgery, The Third Affiliated Hospital, Southern Medical University, 183 West Zhongshan Avenue, Guangzhou, Guangdong, 510630, People’s Republic of China, Email llx0129@i.smu.edu.cn; lxl1979@i.smu.edu.cnBackground: Guanine-rich RNA sequence binding factor 1 (GRSF1), part of the RNA-binding protein family, is now attracting interest due to its potential association with the progression of a variety of human cancers. The precise contribution and molecular mechanism of GRSF1 to colorectal cancer (CRC) progression, however, have yet to be clarified.Methods: Immunohistochemistry and Western Blot analysis was carried out to detect the expression of GRSF1 in CRC at both mRNA and protein levels and its subsequent effects on prognosis. A series of functional tests were performed to understand its influence on proliferation, migration, and invasion of CRC cells.Results: The universal downregulation of GRSF1 in CRC was identified, indicating a correlation with poor prognosis. Our functional studies unveiled that the elimination of GRSF1 enhances tumour activities such as proliferation, migration, and invasion of CRC cells, while GRSF1 overexpression curtailed these abilities.Conclusion: Notably, we uncovered that GRSF1 insufficiency modulates the PI3K/Akt signaling pathway and Ras activation in CRC. Therefore, our data suggest GRSF1 operates as a tumor suppressor gene in CRC and may offer promise as a potential biomarker and novel therapeutic target in CRC management. Keywords: GRSF1, CRC, proliferation, metastasis, Ras/PI3K/Akt

Worms spreading directly between cell-phones over short-range radio (Bluetooth, WiFi, etc.) are increasing rapidly. Communication by these technologies is opportunistic and has very close relation with the social characteristics of the phone carriers. In this paper, we try to evaluate the impact of different characteristics on the spreading performance of worms. On the other hand, the behaviors of worms may have certain impact, too. For example, worms may make phones be completely dysfunctional and these phones can be seen as killed. We study the impact of the killing speed. Using the Markov model, we propose some theoretical models to evaluate the spreading performance in different cases. Simulation results show the accuracy of our models. Numerical results show that if users do not believe the data coming from others easily, the worms may bring less damage. Surprisingly, if the users are more willing to install the anti-virus software, the worms may bring bigger damage when the software becomes to be outdated with high probability. Though the worms can bring big damage on the network temporarily by killing phones rapidly, numerical results show that this behavior may decrease the total damage in the long time. Therefore, killing nodes more rapidly may be not optimal for worms.

Wenjie Xie,1,2,&ast; Yixun Zhang,1,2,&ast; Qianfeng Xu,1,2,&ast; Guowei Zhong,1,2 Jundong Lin,2,3 Huichan He,3 Qiuling Du,2 Huijing Tan,1,2 Muqi Chen,1,2 Zhenjie Wu,1– 3 Yulin Deng,1,2 Zhaodong Han,1– 3 Jianming Lu,1,2,4 Jianheng Ye,1,2,4 Fen Zou,1,2 Yangjia Zhuo,1,2 Weide Zhong1– 4 1Department of Urology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China; 2Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China; 3Urology Key Laboratory of Guangdong Province, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510230, People’s Republic of China; 4State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, 999078, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yangjia Zhuo; WeideZhong, Email eyyangjiazhuo@scut.edu.cn; zhongwd2009@live.cnPurpose: Current treatment approaches for Prostate cancer (PCa) often come with debilitating side effects and limited therapeutic outcomes. There is urgent need for an alternative effective and safe treatment for PCa.Methods: We developed a nanoplatform to target prostate cancer cells based on graphdiyne (GDY) and a copper-based metal-organic framework (GDY-CuMOF), that carries the chemotherapy drug doxorubicin (DOX) for cancer treatment. Moreover, to provide GDY-CuMOF@DOX with homotypic targeting capability, we coated the PCa cell membrane (DU145 cell membrane, DCM) onto the surface of GDY-CuMOF@DOX, thus obtaining a biomimetic nanoplatform (DCM@GDY-CuMOF@DOX). The nanoplatform was characterized by using transmission electron microscope, atomic force microscope, X-ray diffraction, etc. Drug release behavior, antitumor effects in vivo and in vitro, and biosafety of the nanoplatform were evaluated.Results: We found that GDY-CuMOF exhibited a remarkable capability to load DOX mainly through π-conjugation and pore adsorption, and it responsively released DOX and generated Cu+ in the presence of glutathione (GSH). In vivo experiments demonstrated that this nanoplatform exhibits remarkable cell-killing efficiency by generating lethal reactive oxygen species (ROS) and mediating cuproptosis. In addition, DCM@GDY-CuMOF@DOX effectively suppresses tumor growth in vivo without causing any apparent side effects.Conclusion: The constructed DCM@GDY-CuMOF@DOX nanoplatform integrates tumor targeting, drug-responsive release and combination with cuproptosis and chemodynamic therapy, offering insights for further biomedical research on efficient PCa treatment. Keywords: graphdiyne, biomimetic nanoplatform, cuproptosis, chemotherapy, prostate cancer

Yan He,1,&ast; Yulei Tang,1,&ast; Silu Wen,1 Lin Dong,1 Fen Li,1,2 Yuqing Deng,1 Zezhang Tao1 1Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zezhang Tao; Yuqing Deng, Email taozezhang111@163.com; qingerdeng0713@163.comBackground: Allergic rhinitis (AR) is globally recognized as a considerable threat to human health with a rising prevalence and a substantial medical and socioeconomic burden. Numerous studies have emphasized the significance of long noncoding RNAs (lncRNAs) in allergic responses. Hence, this research dealt with exploring the involvement of the lncRNA LINC00998 in the mechanism of AR.Methods: LINC00998 expression was assessed by qRT-PCR in peripheral blood mononuclear cells acquired from individuals with AR. Additionally, the potential relationship between LINC00998 and macrophage polarization was observed in vitro. Then we constructed AR mice model and macrophage polarization models using THP-1 cells as well as primary human macrophages to verify the M2 shift in AR and the low expression level of LINC00998 in M2 macrophages. We used gain- and loss-of-function experiments to explore the modification of LINC00998 in macrophage polarization. Furthermore, we explored the underlying mechanism of LINC00998 mediates through qRT-PCR, flow cytometry, and Western blot.Results: The analysis revealed a significant decrease in LINC00998 expression in the samples obtained from patients with AR. LINC00998 is markedly increased in M1 macrophages whereas decreased in M2 macrophages in vitro. Furthermore, suppression of LINC00998 caused a remarkable enhancement in M2 polarization, whereas its overexpression led to its attenuation. Knockdown of LINC00998 led to a remarkable downregulation of BOB.1 mRNA and protein, while overexpression of LINC00998 upregulated their expression. Moreover, it was found that BOB.1 modulated macrophage polarization through the PU.1/IL-1β axis. Meanwhile, the modulation of LINC00098 overexpression on macrophage polarization and PU.1/ IL-1β can be reversed by BOB.1 siRNA.Conclusion: This research revealed the lncRNA LINC00998 altered M2 macrophage polarization by regulating the BOB.1/PU.1/IL-1β axis, which open up new avenues for studying the pathogenesis of AR. Keywords: allergic rhinitis, allergy, macrophage polarization, LncRNA, LINC00998

Yue Wang,1 Jie Chen,1 Han Dong,2 Rui-Lin Ma,1 Ying Zou,3 Wei Wang,4 Qingmei Zheng,5 Ying Feng,6 Zhangyun Tan,7 Xiaoqin Zeng,8 Yinqing Zhao,7 Yan Deng,1 Yanfang Wang,1 Bei Gu,9 Aijun Sun1,10 1National Clinical Research Center for Obstetric & Gynecologic Diseases Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of Obstetrics and Gynecology, Women and Children’s Hospital of Jinzhou, Jinzhou, Liaoning, 121000, People’s Republic of China; 3Department of Obstetrics and Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, 410008, People’s Republic of China; 4Department of Reproductive Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 5Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266500, People’s Republic of China; 6Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 7Department of Obstetrics and Gynecology, Xinhui Maternity and Children’s Hospital, Nanning, Guangxi, 529100, People’s Republic of China; 8Department of Gynecology, Guangzhou Women and Children’s Medical Center, Guangzhou, Guangdong, 510000, People’s Republic of China; 9Department of Obstetrics and Gynecology, Beijing Shijitan Hospital, Capital Medical University, Peking University Ninth School of Clinical Medicine, Beijing, 100038, People’s Republic of China; 10Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, 100010, People’s Republic of ChinaCorrespondence: Aijun Sun, Email saj@pumch.cnBackground: The basic medical education stage is not enough to support physicians to fully diagnose and evaluate polycystic ovary syndrome (PCOS). The study aims to discover the difference in treatment choice between participants with different annual consultation number of PCOS, to promote lifelong learning, and drive balanced development within healthcare.Methods: This is a multicenter cross-sectional survey. Participants’ basic information, knowledge of PCOS and treatment options were collected online. According to the annual consultation number of patients with PCOS, physicians were divided into three groups: 0– 50 people/yr, 50– 200 people/yr, and > 200 people/yr, and the results were derived from χ2 test, Fisher exact test, and multivariate logistic regression analysis.Results: The study analyzed 1689 questionnaires, and 1206 physicians (71.4%) received less than 50 women per year, 388 physicians (30.0%) with an annual number of 50– 200 women, and 95 physicians (5.6%) with patient turnover for more than 200 people. Reproductive endocrinologists generally have higher access to the clinic. As the number of visits increases, more and more physicians would perceive patients as more likely to have abnormal blood glucose and heavy weight. Physicians with large numbers of consultations are more likely to use Asian or Chinese standards to assess obesity. The multivariate analysis involved variables such as age, hospital level, specialty, and patient turnover annually, and more young doctors actively assessed lipid profile (odds ratio (OR) 1.56, 95% confidence interval (CI) (1.16, 2.16)), and primary hospitals (OR 0.65 CI (0.44, 0.89)) chose OGTT for blood glucose assessment less than tertiary hospitals. Physicians in secondary hospitals are more aggressive in evaluating androgens.Conclusion: Our survey found differences in endocrine assessment, metabolic screening, and treatment in PCOS women in terms of the number of obstetrician-gynecologists who received different patient consultation numbers. The importance of continuing education for physicians is emphasized, to promote lifelong learning.Keywords: polycystic ovary syndrome, consultation number, lifelong learning, insulin resistance, obesity, hyperandrogenemia, metformin

Min Cai,1,&ast; Yue Deng,2,&ast; Tianyang Hu3 1Department of Nephropathy and Rheumatism, Yongchuan Hospital of Chongqing Medical University (The Fifth Clinical College of Chongqing Medical University), Chongqing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Fifth People’s Hospital of Chongqing, Chongqing, People’s Republic of China; 3Precision Medicine Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianyang Hu, Email hutianyang@stu.cqmu.edu.cnPurpose: Acute kidney injury (AKI) is a common complication of acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and inflammation is the potential link between AKI and AECOPD. However, little is known about the incidence and risk stratification of AKI in critically ill AECOPD patients. In this study, we aimed to establish risk model based on white blood cell (WBC)-related indicators to predict AKI in critically ill AECOPD patients.Material and Methods: For the training cohort, data were taken from the Medical Information Mart for eICU Collaborative Research Database (eICU-CRD) database, and for the validation cohort, data were taken from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. The study employed logistic regression analysis to identify the major predictors of WBC-related biomarkers on AKI prediction. Subsequently, a risk model was developed by multivariate logistic regression, utilizing the identified significant indicators.Results: Finally, 3551 patients were enrolled in training cohort, 926 patients were enrolled in validation cohort. AKI occurred in 1206 (33.4%) patients in training cohort and 521 (56.3%) patients in validation cohort. According to the multivariate logistic regression analysis, four WBC-related indicators were finally included in the novel risk model, and the risk model had a relatively good accuracy for AKI in the training set (C-index, 0.764, 95% CI 0.749– 0.780) as well as in the validation set (C-index, 0.738, 95% CI: 0.706– 0.770). Even after accounting for other models, the critically ill AECOPD patients in the high-risk group (risk score > 3.44) still showed an increased risk of AKI (odds ratio: 4.74, 95% CI: 4.07– 5.54) compared to those in low-risk group (risk score ≤ 3.44). Moreover, the risk model showed outstanding calibration capability as well as therapeutic usefulness in both groups for AKI and ICU mortality and in-hospital mortality of critical ill AECOPD patients.Conclusion: The novel risk model showed good AKI prediction performance. This risk model has certain reference value for the risk stratification of AECOPD complicated with AKI in clinically.Keywords: risk model, acute kidney injury, prediction, white blood cell, acute exacerbation of chronic obstructive pulmonary disease

Yuhan Wang,1,&ast; Ping Zhang,1,&ast; Yu Lv,1 Yu Deng,2 Ming Yao,3 Lin Wang,1 Guangtao Pan3 1College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei Province, People’s Republic of China; 2Department of Encephalopathy, Guangzhou Hospital of Integrated Traditional and West Medicine Affiliated to Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Department of Dermatology, Yancheng Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangtao Pan, Department of Dermatology, Yancheng Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, No. 53, Renmin North Road, Tinghu District, Yancheng, Jiangsu Province, People’s Republic of China, Tel +86-17612738767, Email panguangtaowuhan@foxmail.comAbstract: This literature review systematically searched relevant literature from the past 10 years using various medical databases, including PubMed, Medline, Cochrane, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu. As a chronic inflammatory disease, psoriasis is associated with various cells and cytokines of the body’s immune system, making them more susceptible to various systemic comorbidities than the general population. At a time when conventional regimens are ineffective and there is a lack of personalized treatment options for such comorbidities, the development of biologics has revolutionized the treatment of psoriasis comorbidities, and a number of biologic combination therapies have been incorporated into first-line treatments in many countries. The focus of this review was to investigate the relationship between psoriasis and comorbidities, such as metabolic syndrome, psoriatic arthritis, cardiovascular diseases, mental disorders, infectious diseases, digestive system diseases, and renal diseases. Furthermore, the study explored the significance of biologic therapies in the management of these comorbidities. Also this paper suggests current conditions and precautions for the use of biologic therapies to minimize the occurrence of adverse effects. This review was performed to provide guidance for clinical drug selection in patients with psoriasis and comorbidities, as well as serve as a reference for the development and application of biologic therapies.Keywords: psoriasis, biologics, comorbidity, research advancements