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Jiajia Zhou,1,2,* Shuang Song,2,3,* Senlin Xue,2 Yingxing Zhu,3 Boyin Xu,4 Ping Ma,2,3 Yanguan Lv,1 Haiquan Kang2,3 1The Huai’an Maternity and Child Clinical College of Xuzhou Medical University, Huai’an, People’s Republic of China; 2Medical Technology School, Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Department of Clinical Laboratory, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China; 4Department of Infection Control, Affiliated Hospital of Nantong University, Nantong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haiquan Kang, Department of Clinical Laboratory, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, People’s Republic of China, Tel +86-516 85802759, Email hqk811029@163.com Yanguan Lv, The Huai’an Maternity and Child Clinical College of Xuzhou Medical University, Huai’an, 223001, People’s Republic of China, Tel +86-517 89687770, Email lvyanguan@163.comBackground: The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has garnered international concern due to its significant antibiotic resistance. Notably, children exhibit distinct resistance mechanisms compared to adults, necessitating a differential approach to antibiotic selection. A thorough analysis of CRKP’s epidemiology and drug resistance mechanisms is essential for establishing a robust foundation for clinical anti-infection strategies and precise prevention and control measures.Methods: This study involved the collection of 31 non-repetitive strains from pediatric and adult patients at a tertiary hospital in China, spanning from July 2016 to July 2022, testing for resistance genes, antimicrobial susceptibility, and homology analysis.Results: Infants (0– 1 year) were the largest pediatric CRKP group, with 61.3% of cases. The neonatal intensive care unit (NICU) and pediatrics were the main departments affected. Adults with CRKP had a mean age of 67 years, with the highest prevalence in neurology and emergency ICU. Antimicrobial susceptibility testing revealed that adult CRKP strains exhibited higher resistance to amikacin, ciprofloxacin, cotrimoxazole, and aztreonam compared to pediatric strains. Conversely, pediatric strains showed a higher rate of resistance to ceftazidime/avibactam. The predominant resistance genes identified were blaNDM-5 in children (58.1%) and blaKPC-2 in adults (87.1%), with over 93% of both groups testing positive for extended-spectrum beta-lactamase (ESBL) genes. Multilocus Sequence Typing (MLST) indicated ST2735 and ST11 as the predominant types in children and adults, respectively. Pulsed-field gel electrophoresis (PFGE) identified clonal transmission patterns of ST11 blaKPC-2 and ST15 blaOXA-232 across both age groups. Notably, this study reports the first instance of ST1114-type CRKP co-producing blaNDM-5 and blaOXA-181 in the NICU.Conclusion: This study reveals distinct resistance mechanisms and epidemiology in CRKP from children and adults. The identified clonal transmission patterns emphasize the need for improved infection control to prevent the spread of resistant strains.Keywords: children, adults, Klebsiella pneumoniae, carbapenemases, drug resistance mechanisms

Zhipeng Liu,1,&ast; Xinyu Yuan,2,&ast; Yan Huang,3 Zihan Gu,4 Lu Xue,5 Shanshan Xue,6 Jun Wang2 1Information Department, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu Province, 225300, People’s Republic of China; 2Emergency Department, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu Province, 225300, People’s Republic of China; 3Medical College, Yangzhou University, Yangzhou, 225009, People’s Republic of China; 4Nanjing University of Finance & Economics, Nanjing, 210023, People’s Republic of China; 5Department of Critical Care Medicine, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu Province, 225300, People’s Republic of China; 6Institute of Clinical Laboratory, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu Province, 225300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Wang; Shanshan Xue, Email 15061008998@163.com; 245116999@qq.comBackground: Sepsis refers to a life-threatening organ dysfunction which can be resulted from the infection-induced dysregulated host response. A large number of inflammatory cytokines are released to act on the liver, making the liver one of the common target organs for the development of multiple organ dysfunction syndrome (MODS) in patients with sepsis. Sepsis-induced acute liver injury (SALI) can aggravate systemic disease. As a result, it is of great clinical significance to comprehend the molecular biological mechanism of SALI and to identify the markers for evaluating SALI. Interferon-induced proteins with tetratricopeptide repeats 1 and 2 (IFIT1, IFIT2) have been recognized as the anti-inflammatory factors that are widely expressed in various organs. The present study was aimed at clarifying the roles of IFIT1 and IFIT2 in the development of SALI.Methods: A two-sample Mendelian randomization (MR) analysis was employed. Summary statistics datas were obtained from GWAS for inflammatory factors [tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6)], IFIT2, and sepsis as well as liver injury. Independent SNPs were selected as instrumental variables (IVs). Inverse variance weighted (IVW) in the MR analysis was adopted as the primary method for estimating the causal associations of inflammatory factors and IFIT2 with two diseases, and the associations of inflammatory factors with IFIT2. Additionally, weighted median method, MR-Egger and sensitivity analyses were applied in assessing the robustness of the results and ensure the result reliability. Subsequently, 119 healthy volunteers, 116 patients with sepsis and 116 SALI patients were recruited. The ELISA method was employed to quantify the expression levels of TNF-α, IL-1β, and IL-6. Additionally, qRT-PCR was conducted to measure the expression of IFIT1 and IFIT2. Furthermore, the correlations of IFIT1 and IFIT2 with inflammatory factors, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were explored.Results: As shown by the MR analysis, the genetically predisposed sepsis was significantly associated with the risk of IL-1β, with an odds ratio (OR) of 1.069 (95% confidence interval (CI), 1.015– 1.127, p = 0.0119), and negatively associated with the risk of IL-6, with an OR of 0.880 (95% CI: 0.792– 0.979, p= 0.0184). Meanwhile, there were positive causal effects of IL-6 (OR = 1.269, 95% CI: 1.032– 1.561, p= 0.0238), IL-1β (OR = 1.106, 95% CI: 1.010– 1.211, p = 0.0299) and IFIT2 (OR = 1.191, 95% CI: 1.045– 1.359, p = 0.0090) on liver injury. Additionally, there was a positive causal effect of IFIT2 (OR = 1.164, 95% CI: 1.035– 1.309, p= 0.0110) on IL-1β. Upon sensitivity analyses, there was weak evidence of such effects, indicating that the findings of this study were robust and reliable. Our results revealed the elevated levels of TNF-α, IL-1β, and IL-6 in the blood samples of sepsis and SALI patients (p < 0.0001). Conversely, IFIT1 and IFIT2 demonstrated the significantly decreased levels in peripheral blood mononuclear cells (PBMCs) of SALI patients (p < 0.0001). Furthermore, the expression levels of IFIT1 and IFIT2 were both negatively correlated with ALT activity (r = − 0.3426, p = 0.0002; r = − 0.3069, p = 0.0008) and AST activity (r = − 0.2483, p = 0.0072; r = − 0.3261, p = 0.0004), respectively. Moreover, the expression of IFIT1 and IFIT2 was both negatively related to the levels of TNF-α (r = − 0.5027, p < 0.0001; r = − 0.4218, p < 0.0001), IL-1β (r = − 0.3349, p = 0.0002; r = − 0.4070, p < 0.0001) and IL-6 (r = − 0.2734, p = 0.0030; r = − 0.3536, p < 0.0001), respectively.Conclusion: IFIT1 and IFIT2 can serve as the diagnostic markers for sepsis-related liver injury, and IFIT1 and IFIT2 may participate in the pathological process of sepsis-related liver injury by regulating inflammation and liver function.Keywords: acute liver injury, sepsis, IFIT1, IFIT2, inflammation, Mendelian randomization

Tongchao Jiang,1,&ast; Haishuang Sun,2,&ast; Tiankai Xu,1 Shuyu Xue,1 Wen Xia,2 Xiang Xiao,1 Ying Wang,1 Ling Guo,3 Huanxin Lin1 1Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 3Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huanxin Lin, Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China, Email linhx@sysucc.org.cn Ling Guo, Department of Nasopharyngeal Carcinoma, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China, Email guoling@sysucc.org.cnBackground: The C-reactive protein-albumin-lymphocyte (CALLY) score is a novel indicator associated with inflammation, immunity, and nutrition, utilized for cancer prognostic stratification. This study aimed to evaluate the integrated prognostic significance of the pre-treatment CALLY score and Epstein-Barr virus (EBV) DNA levels in nasopharyngeal carcinoma (NPC) patients and to develop prognostic models.Patients and Methods: A total of 1707 NPC patients from September 2015 to December 2017 were retrospectively enrolled. The cut-off point for the CALLY score, determined by maximum selected rank statistics, integrates with the published cut-off point for pre-EBV DNA to develop a comprehensive index. Subsequently, patients were randomly allocated in a 1:1 ratio into training and validation cohorts. Survival analysis was conducted using the Kaplan-Meier method with Log rank tests, and the Cox proportional hazards model was applied to identify independent prognostic factors for constructing predictive nomograms. The predictive ability of the nomograms were assessed through the concordance index (C-index), calibration curves, and decision curve analysis.Results: By integrating CALLY scores and EBV-DNA levels, patients were categorized into three risk clusters. Kaplan-Meier curves reveal significant differences in overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) outcomes among different risk groups (all P values < 0.05). Multivariate analysis revealed that CALLY-EBV DNA index serves as an independent prognostic factor for the OS, DMFS, and LRRFS. The prognostic nomograms based on the CALLY-EBV DNA index provided accurate predictions for 1-year, 3-year, and 5-year OS, DMFS, and LRRFS. Additionally, compared to the traditional TNM staging system, the nomograms exhibited enhanced discriminatory power, calibration capability, and clinical applicability. All results were in agreement with the validation cohort.Conclusion: The CALLY-EBV DNA index is an independent prognostic biomarker. The nomogram prediction models, constructed based on the CALLY-EBV DNA index, demonstrates superior predictive performance compared to the traditional TNM staging.Keywords: CALLY score, EBV DNA, nasopharyngeal carcinoma, biomarker, prognostic model

Qianqian Liang,1– 3 Difang Sun,1– 3 Shuyue Xue,1– 3 Xinying Li,1– 3 Xin Liu,1– 3 Qing Du,1– 3 Zhichun Zhang,1– 3 Xiubin Ma,1– 3 Jun Li1– 3 1Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, Qingdao, Shandong, People’s Republic of China; 2State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Qingdao, Shandong, People’s Republic of China; 3School of Ophthalmology, Shandong First Medical University, Qingdao, Shandong, People’s Republic of ChinaCorrespondence: Jun Li; Xiubin Ma, Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, Qingdao, 266071, People’s Republic of China, Tel +86-532-85876380, Email doctor_li@126.com; maxiubin2005@126.comPurpose: To compare the effectiveness and safety of adjustable and free postoperative positioning after pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD).Design: Prospective, randomized controlled study.Methods: A total of 94 eyes with RRD were enrolled from April 2020 to April 2023 and monitored postoperatively for at least 3 months. All patients underwent PPV combined with silicone oil injection or gas tamponade and were randomly divided postoperatively into two groups: an adjustable positioning group and a free positioning group. The success of the outcome was based on the retinal reattachment rate, best corrected visual acuity (BCVA), postoperative complications, and ocular biometric parameters such as anterior chamber depth (ACD) and lens thickness (LT).Results: The initial retinal reattachment rate was 97.9% in the adjustable positioning group and 95.7% in the free positioning group, manifesting no statistical difference between the two groups. Similarly, no statistical difference was observed between the two groups in the final BCVA, which was significantly improved compared to the preoperative BCVA. The comparison of the 1-month postoperative ACD and LT with the preoperative values showed no statistically significant differences in the two groups. The rates of complications were not statistically different in the two groups.Conclusion: After treating RRD using PPV, neither the adjustable nor the free postoperative positioning affected the retinal reattachment rate or the incidence of complications. Therefore, our study showed that it is safe and effective to adopt free positioning postoperatively, which may provide more options for patients with RRD undergoing PPV.Keywords: rhegmatogenous retinal detachment, pars plana vitrectomy, adjustable positioning, free positioning

Fenglei Wang, Zhiying Yu, Shasha Xue, Yunxiao Wang, Lin Li, Dabo Wang, Ling Wang Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Ling Wang, Department of Ophthalmology, the Affiliated Hospital of Qingdao University, University, No. 16 Jiangsu Road, Shinan District, Qingdao, 266003, People’s Republic of China, Tel +86 18661806679, Email tsingtaowl@hotmail.comPurpose: To investigate the differences in parameters related to angle configuration and lens position in patients with cortical age-related cataract by ultrasound biomicroscopy (UBM) in different body positions.Methods: Prospective study with 55 patients with cortical age-related cataract proposed for phacoemulsification, examined using a Compact Touch STS UBM (Quantel Medical, France). UBM bag/balloon technology was applied to measure the central anterior chamber depth (ACD) and lens vault (LV) in horizontal and vertical orientation in sitting and supine positions, angle opening distance (AOD500), trabecular iris angle (TIA) and iris lens angle (ILA) in four quadrants: superior, inferior, nasal, and temporal.Results: We found no significant difference in ACD between sitting and supine positions (p = 0.053); LV was significantly greater in the supine position (p < 0.001); AOD500 in superior and inferior quadrants were significantly longer in the sitting position (p = 0.001; p < 0.001); TIA in superior and inferior quadrants was significantly greater in the sitting position (p < 0.001; p < 0.001), and TIAmax-min was significantly smaller in the sitting position (p = 0.001); ILA in temporal quadrant was significantly larger in the sitting position (p = 0.015) and ILAmax-min was significantly smaller in the sitting position (p < 0.001).Conclusion: The anterior chamber angle was narrower and the lens was positioned more anteriorly in the supine than in the sitting position in cortical age-related cataract. Different positions may affect the angle configuration and the relative space of lens through different directions of mechanics and modes of action.Keywords: angle configuration, body position, ultrasound biomicroscopy, cortical age-related cataract

Energy-dense food alters dopaminergic (DA) transmission in the mesocorticolimbic (MCL) system and can promote reward dysfunctions, compulsive feeding, and weight gain. Yet the mechanisms by which nutrients influence the MCL circuitry remain elusive. Here, we show that nutritional triglycerides (TGs), a conserved post-prandial metabolic signature among mammals, can be metabolized within the MCL system and modulate DA-associated behaviors by gating the activity of dopamine receptor subtype 2 (DRD2)-expressing neurons through a mechanism that involves the action of the lipoprotein lipase (LPL). Further, we show that in humans, post-prandial TG excursions modulate brain responses to food cues in individuals carrying a genetic risk for reduced DRD2 signaling. Collectively, these findings unveil a novel mechanism by which dietary TGs directly alter signaling in the reward circuit to regulate behavior, thereby providing a new mechanistic basis by which energy-rich diets may lead to (mal)adaptations in DA signaling that underlie reward deficit and compulsive behavior.

Yan Li,1,2 Xiaopeng Chen,1,3 Rujuan Zhou,2 Wu Xu,2 Xiaorong Wang,2 Wa Chao,1 Shouru Xue1 1Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Neurology, The Taixing People’s Hospital, Taixing, People’s Republic of China; 3Department of Neurology, The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, People’s Republic of ChinaCorrespondence: Shouru Xue, Department of Neurology, The First Affiliated Hospital of Soochow University, No. 188 Shizi Road, Suzhou, 215006, People’s Republic of China, Tel +86-18962133036, Fax +86-512-65223637, Email xueshouru@suda.edu.cnPurpose: This study aimed to investigate the relationship between cognitive impairment and homocysteine (Hcy) and S100B protein in patients with progressive ischemic stroke (PIS).Patients and Methods: A total of 158 patients with PIS hospitalized in the Department of Neurology in Taixing People’s Hospital from January 2020 to March 2022 were enrolled in the study. After 90 days of follow-up, the patients were divided into two groups according to the MoCA score— 99 cases with cognitive impairment group (observation group) and 59 cases with cognitive normal group (control group). Causal diagram was drawn to assess the association between risk factors and PIS with observation group. The risk factors indicators of cognitive impairment in patients with PIS were screened. The related predictive indicators were screened by multivariate logistic regression analysis, and Pearson correlation analysis. The predictive value was analyzed by Receiver Operating Characteristic (ROC) curve.Results: Multivariate logistic regression analysis showed that age, hypertension, lesion position, Hcy and S100B protein were related risk factors for cognitive impairment in patients with PIS. Pearson correlation analysis was conducted between Hcy and S100 B protein and MoCA score, and revealed that Hcy and S100 B protein were negatively correlated with MoCA score. ROC curve analysis showed that the Area Under the Curve (AUC) of S100 B protein and Hcy in identifying cognitive impairment after PIS was 0.709 and 0.673, respectively, and the combined AUC of Hcy and S100B protein in predicting cognitive impairment after PIS was 0.739.Conclusion: Hcy and S100B protein are related risk factors for cognitive impairment in patients with PIS, and may be used as in a prediction model to predict cognitive impairment after PIS in the future.Keywords: progressive ischemic stroke, cognitive impairment, homocysteine, S100B protein

Shuang Xue,1,2 Michelle R Kaufman,3 Xing Zhang,4 Shunan Xia,5 Chengcheng Niu,6 Rui Zhou,7 Wenjian Xu1,2 1Department of Sociology & Psychology, School of Public Administration, Sichuan University, Chengdu, People’s Republic of China; 2Institute of Psychology, Sichuan University, Chengdu, People’s Republic of China; 3Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; 4School of Psychology, Jiangxi Normal University, Nanchang, People’s Republic of China; 5School of Social Development and Public Policy, Fudan University, Shanghai, People’s Republic of China; 6Faculty of Psychology, Southwest University, Chongqing, People’s Republic of China; 7College of Marxism, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Wenjian Xu; Rui Zhou, Email xuwenjian@scu.edu.cn; ruizhou_283@163.comPurpose: Suffering during events such as the COVID-19 pandemic threatens university students’ physical and psychological health. Given the literature indicating the protective role of resilience and social support, the current study explored the mediating and moderating roles of social support in the association between resilience and prosocial behavior among university students in mainland China during COVID-19 mitigation.Methods: We conducted an online survey using convenience sampling from 23rd February to 3rd March 2020 among Chinese university students who had encountered home-quarantine due to the COVID-19 pandemic. Self-report scales were used to measure levels of resilience (Connor-Davidson Resilience Scale), social support (the Social Support Scale), and prosocial behavior (Prosocial Tendencies Measure). A total of 313 university students participated in this online survey. Hayes PROCESS macro for SPSS was used to test the hypothesized mediating and moderating effects of social support in the relationship between resilience and prosocial behavior.Results: Pearson’s correlations analysis showed that all outcomes of interest were positively associated. Importantly, social support (subjective support, objective support, and support utilization) mediated the indirect link of resilience with prosocial behavior. Furthermore, moderation analyses indicated that support utilization played a moderating role in this link. Support utilization may reduce the negative influence of COVID-19 on university students’ prosocial behavior and serve as a protective factor between resilience and prosocial behavior in highly stressful contexts.Conclusion: Our findings enrich research on prosocial behavior by investigating the potential internal and external variables that influence such behavior during periods of suffering. Findings also provide evidence for the need to promote university students’ prosocial behavior.Keywords: COVID-19, resilience, social support, prosocial behavior, mediation and moderation

Xiaopeng Chen,1,2 Guoqiang Ren,3 Yan Li,1,4 Wa Chao,1 Siyuan Chen,2 Xuezhong Li,2 Shouru Xue1 1Department of Neurology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Neurology, the Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 3Department of Radiology, the Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 4Department of Neurology, the Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of ChinaCorrespondence: Shouru Xue, Department of Neurology, the First Affiliated Hospital of Soochow University, No. 188 Shizi Road, Suzhou, Jiangsu Province, 215006, People’s Republic of China, Tel +86-18962133036, Fax +86-512-65223637, Email xueshouru@suda.edu.cnPurpose: We evaluated the diagnostic value of long non-coding RNA growth arrest-specific transcript 5 (GAS5) and its relationship with hippocampal volume in Alzheimer’s disease (AD).Patients and Methods: One hundred and eight patients with AD and 83 healthy controls were included, and demographic data, biochemical parameters, GAS5 levels, and hippocampal volume were recorded. Chi-squared tests or independent sample t-tests were used to compare the baseline characteristics, relative expression of GAS5, and hippocampal volume. Correlations between variables were determined using Spearman’s rank correlation test. Receiver operating characteristic (ROC) curves were generated to compare the diagnostic value of GAS5 and total hippocampal volume in AD.Results: The levels of GAS5 were significantly upregulated in patients with AD compared with those in controls and were negatively correlated with MMSE score. There were differences in left hippocampal volume, right hippocampal volume, and total hippocampal volume between the two groups. Total hippocampal volume was positively correlated with MMSE score and negatively correlated with GAS5 expression in patients with AD. The area under the curve (AUC) of for GAS5 expression was 0.831, the sensitivity was 61.1%, and the specificity was 95.2%. The AUC of the combined total hippocampal volume was 0.891, the sensitivity was 74.1%, and the specificity was 92.8%.Conclusion: The results suggested that GAS5 may be an excellent indicator of AD progression alone or in combination with hippocampal volume.Keywords: Alzheimer’s disease, long non-coding RNA, receiver operating characteristic, biomarker

Wei Tang,1,&ast; Qian Lv,1,&ast; Xiao Huang,2,&ast; Yuzhen Li,2 JunJie Zou,1 Jiaoyang Zheng,1 Liangliang Sun,1 Yi Bao,1 Haiyan Chen,1 Tuo Li,1 Bei Zhang,1 Song Xue,1 Yan Song,1 Xingxing Zhang,1 Xiangfang Chen,1 Jiping Cai,2 Yongquan Shi1 1Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, People’s Republic of China; 2Department of Ophthalmology, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangfang Chen; Yongquan Shi, Department of Endocrinology, Second Affiliated Hospital of Naval Medical University, No. 415 Fengyang Road, Huangpu District, Shanghai, 200003, People’s Republic of China, Email chenxiangfang@smmu.edu.cn; young.stone@smmu.edu.cnObjective: Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease that involves the remodeling of orbit and periorbital tissues. Thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R) may stimulate the activation of autoimmunity in TAO, but the exact mechanism is unclear. We investigated whether IGF-1R/TSHR modulation in TAO may involve microRNA regulation.Methods: We conducted microarray analysis using RNA from the orbital connective tissue samples of 3 healthy and 3 patients with TAO. The involvement of differentially regulated microRNA in IGF-1R/TSHR modulation in TAO was evaluated in orbital fibroblasts (OFs) and female BALB/c mice.Results: Using hierarchical cluster analysis, we identified that miR-143 was downregulated in TAO. The expression levels of miR-143 in OFs were significantly reduced under IL-1B stimulation. However, OF proliferation and inflammatory responses decreased when miR-143 is overexpressed. In contrast, the suppression of miR-143 increased levels of inflammatory markers (IL-6, IL-8, MCP1) and hyaluronan accumulation. Moreover, overexpression of miR-143 significantly lowers levels of IGF-1R and TSHR. A luciferase assay indicated that miR-143 targets the 3′-UTR of IGF-1R. Increases in the expression of IGF-1R increased the expression of the inflammasome marker NLRP3 and apoptotic marker cleaved caspase-1; however, miR-143 overexpression decreased levels of IGF-1R, TSHR, NLRP3, cleaved caspase 1, IL-1B, and IL-18. In a mouse model of TAO, overexpression of miR-143 significantly reduced levels of IGF-1R and attenuated the adipogenesis associated with TAO.Conclusion: We found that miR-143 directly targets IGF-1R to alleviate the inflammatory response in TAO by indirectly decreasing levels of TSHR and inactivating NLRP3.Keywords: thyroid-associated ophthalmopathy, miR-143, thyroid-stimulating hormone receptor, insulin-like growth factor 1 receptor, NLRP3

Li Gu,1 Song Xue2 1Department of Endocrinology, People’s Hospital of Gaochun, Nanjing, 211300, People’s Republic of China; 2Department of Pathology, People’s Hospital of Gaochun, Nanjing, 211300, People’s Republic of ChinaCorrespondence: Li GuDepartment of Endocrinology, People’s Hospital of Gaochun, No. 53 Maoshan Road, Gaochun District Economic Development Zone, Nanjing, 211300, People’s Republic of ChinaTel +86 13851529447Email Rougu_doct@163.comPurpose: Red cell distribution width (RDW) has been evidenced to be related to various diabetes-associated macrovascular and microvascular complications. However, the studies on the association between RDW and diabetic chronic kidney disease (CKD) are still scarce. The aim of the study is to explore whether there is any association between RDW and the severity of diabetic CKD.Patients and Methods: The study recruited 396 patients diagnosed with diabetic CKD at People’s Hospital of Gaochun from January 2006 to April 2021. Baseline characteristics were gathered and laboratory tests were performed to measure clinical indexes. Patients were also categorized into three groups based on their CKD stages. Correlation analysis and multivariate ordinal logistic regression were performed to investigate the association between RDW and the severity of diabetic CKD. The risk size was described as odds ratio (OR) and 95% confidence interval (CI).Results: We found a significant association between RDW and the severity of CKD, with a correlation coefficient of 0.32 (P < 0.01). We used three models for multivariate ordinal logistic regression to investigate the relationship between RDW and the severity of CKD. Results showed that RDW is an independent and significant risk factor of diabetic CKD after adjustment for demographic data, physiological indexes, and drug history [Model 3 OR (95% CI) = 1.225 (1.023– 1.467)]. In subgroup analysis, RDW remained a significant risk factor in all three models for patients who had diabetes of 5– 10 years [Model 3 OR (95% CI) = 1.480 (1.067– 2.052)] and had a HbA1c level > 7% [(Model 3 OR (95% CI) = 1.478 (1.184– 1.845)].Conclusion: RDW is significantly associated with the disease stages of diabetic CKD, and the risk is higher for people with 5– 10 years of diabetes and for those who do not control the HbA1c level well. This study has implications for the diagnosis, monitoring, and timely treatment of the diabetic CKD.Keywords: red cell distribution width, diabetic chronic kidney disease, correlation, inflammation

Sijia Ma,1 Mingming Zhao,1 Jiao Fan,1 Meiying Chang,1 Zhiyu Pan,1 Ziyan Zhang,1 Shunxuan Xue,1 Qi Li,2 Yu Zhang1 1Department of Nephrology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Yu Zhang Email zhangyu8225@126.comIntroduction: Renal clear cell carcinoma (ccRCC) is a common tumor of the urinary system, most of which are primary malignant tumors with high metastatic rate and remaining incurable. Ferroptosis is a newly discovered form of iron-dependent programmed cell necrosis in recent years, which is inextricably linked to the occurrence and development of tumors progression. Due to the complexity of the interaction between genes in ccRCC, the research on the pathogenesis of ccRCC is still not remarkably accurate. Therefore, whether ferroptosis-related genes (FRGs) can play a role in predicting prognosis in ccRCC needs to be discussed.Methods: We entered the Cancer Genome Mapping Project (TCGA) database and downloaded the relevant genes and clinical research data of ccRCC patients. Lasso Cox regression was used to construct a multi-gene prognostic model in the TCGA cohort. R language software was used for drawing pictures related to our study.Results: Most of the genes involved in ferroptosis (86.2%) existing differences between the tumor and normal tissues in the TCGA public gene database. In terms of univariate Cox regression analysis, 20 differentially expressed genes (DEGs) were associated with prognosis and survival (P< 0.05). A prognostic model of 12 FRGs was constructed, and patients were segmented into two different groups depending on how risky they are. Considering overall survival, the high-risk group is dramatically lower than the low-risk group (P< 0.001). In multivariate Cox regression analysis, risk scores and stage turned out be an independent prognostic factor (P< 0.001). GO and KEGG analysis and ssGSEA analysis of DEGs revealed that these genes were related to immune-related pathways (P< 0.05).Conclusion: This study established and identified the changes in FRGs expression and prognostic factors of ccRCC, which can be helpful for prognosis evaluation and clinical treatment of this disease.Keywords: renal clear cell carcinoma, ferroptosis, TCGA database, the prognosis

Guomei Shi,1,2,&ast; Wenxiu Chen,3,&ast; Pengyu Gong,4 Meng Wang,4 Junshan Zhou,4 Xiaorong Wang,1 Minwang Guo,1 Jingye Lu,1 Yan Li,1 Hongxuan Feng,2,5 Xuetao Fu,2,6 Rujuan Zhou,1 Shouru Xue2 1Department of Neurology, The Taixing People’s Hospital, Taixing, Jiangsu, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 3Department of Critical Care Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5Department of Neurology, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, People’s Republic of China; 6Department of Neurology, Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rujuan Zhou; Shouru Xue Tel +86-13951158499; +86-18962133036Email zhourujuan123@163.com; xueshouru@suda.edu.cnBackground: Stroke-associated pneumonia (SAP) is a standout complication after acute ischemic stroke (AIS), with a prevalence of 7– 38%. The aim of this prospective study was to investigate the relationship between serum YKL-40 levels at admission and SAP.Methods: Between August 2020 and February 2021, consecutive AIS patients from two centers were enrolled prospectively. Serum YKL-40 concentrations were measured via enzyme-linked immunosorbent assay. We performed logistic regression analyses to explore the relationship between YKL-40 and SAP. Receiver operating characteristic curve was also used to assess the predictive ability of YKL-40 in predicting SAP.Results: Ultimately, a total of 511 AIS patients were recruited. Multivariate logistic regression analysis showed that YKL-40 was independently related to SAP, whether as a continuous variable or as quartiles (P=0.001). The area under curve of YKL-40 to predict SAP was 0.765. The optimal cutoff value of YKL-40 as a predictor of SAP was determined to be 206.4 ng/mL, where the sensitivity was 63.1% and the specificity was 82.0%.Conclusion: Our study demonstrated that YKL-40 might be considered as a useful biomarker to predict SAP in AIS patients.Keywords: acute ischemic stroke, YKL-40, stroke-associated pneumonia

Lei Yang, Song Xue, Mingjun Du, Feng Lian Department of Cardiovascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, People’s Republic of ChinaCorrespondence: Feng Lian Email dr.lianfeng@hotmail.comIntroduction: The reprogramming of induced cardiomyocytes (iCMs) is of particular significance in regenerative medicine; however, it remains a great challenge to fabricate an efficient and safe gene delivery system to induce reprogramming of iCMs for therapeutic applications in heart injury. Here, we report branched polyethyleneimine (BP) coated nitrogen-enriched carbon dots (BP-NCDs) as highly efficient nanocarriers loaded with microRNAs-combo (BP-NCDs/MC) for cardiac reprogramming.Methods: The BP-NCDs nanocarriers were prepared and characterized by several analytical techniques.Results: The BP-NCDs nanocarriers showed good microRNAs-combo binding affinity, negligible cytotoxicity, and long-term microRNAs expression. Importantly, BP-NCDs/MC nanocomplexes led to the efficient direct reprogramming of fibroblasts into iCMs without genomic integration and resulting in effective recovery of cardiac function after myocardial infarction (MI).Conclusion: This study offers a novel strategy to provide safe and effective microRNAs-delivery nanoplatforms based on carbon dots for promising cardiac regeneration and disease therapy.Keywords: nitrogen-enriched carbon dots, branched polyethyleneimine, microRNAs, direct reprogramming, induced cardiomyocytes