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Approaches to quantify stress responses typically rely on subjective surveys and questionnaires. Wearable sensors can potentially be used to continuously monitor stress-relevant biomarkers. However, the biological stress response is spread across the nervous, endocrine, and immune systems, and the capabilities of current sensors are not sufficient for condition-specific stress response evaluation. Here we report an electronic skin for stress response assessment that non-invasively monitors three vital signs (pulse waveform, galvanic skin response and skin temperature) and six molecular biomarkers in human sweat (glucose, lactate, uric acid, sodium ions, potassium ions and ammonium). We develop a general approach to prepare electrochemical sensors that relies on analogous composite materials for stabilizing and conserving sensor interfaces. The resulting sensors offer long-term sweat biomarker analysis of over 100 hours with high stability. We show that the electronic skin can provide continuous multimodal physicochemical monitoring over a 24-hour period and during different daily activities. With the help of a machine learning pipeline, we also show that the platform can differentiate three stressors with an accuracy of 98.0%, and quantify psychological stress responses with a confidence level of 98.7%.

Ting-Ting Ni, Yuan-Yuan Yao, Xiao-Xia Zhou, Tao Lv, Jing-Cheng Zou, Ge Luo, Jin-Ting Yang, Da-Wei Sun, Qi Gao, Ting-Ting Wang, Rui-Yu Wang, Xin-Chen Tao, Min Yan Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, 330100, People’s Republic of ChinaCorrespondence: Min Yan, Department of Anesthesiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou, Zhejiang, 330100, People’s Republic of China, Email zryanmin@zju.edu.cnPurpose: Postinduction hypotension (PIH), occurring between anaesthesia induction and surgical incision, is particularly concerning in older adults undergoing transcatheter aortic valve replacement (TAVR) due to their multiple comorbidities and age-related cardiovascular changes. This study aimed to assess the relationship between PIH and postoperative adverse events in TAVR patients.Patients and Methods: A total of 777 patients underwent TAVR at The Second Affiliated Hospital of Zhejiang University School of Medicine from January 1, 2020 to February 28, 2023. Four thresholds of MAP were defined, including two absolute thresholds (< 65, < 60 mmHg) and two relative thresholds (20% and 30% lower than baseline). The relationships between PIH and the composite outcome, which included all-cause in-hospital mortality, stroke, acute kidney injury (AKI), and myocardial infarction (MI), were examined using unadjusted analysis, 1:1 propensity score matching(PSM), and inverse probability of treatment weighting (IPTW).Results: A total of 643 older adults were included in the study ultimately. The composite outcome incidence was significantly greater in patients with PIH than in those without PIH (relative risk [RR]: 2.47, 95% CI: 1.66– 3.73 for MAP < 60 mmHg; RR: 1.66, 95% CI: 1.14– 2.46 for a > 30% decrease from baseline). PIH was significantly associated with stroke (RR: 5.22, 95% CI: 1.98– 17.75) and AKI (RR: 2.82, 95% CI: 1.73– 4.79) with a MAP < 60 mmHg.Conclusion: PIH significantly increases the risk of composite outcomes, especially stroke and AKI, in TAVR patients.Keywords: postinduction hypotension, adverse postoperative outcomes, transcatheter aortic valve replacement, older adults

Jie Ding,1,&ast; Fu-Ping Chen,1,&ast; Ya-Ying Song,1,&ast; Hong-Yan Li,1 Xi-Wen Ai,1 Yi Chen,1 Lu Han,1 Xia-Jun Zhou,1 De-Sheng Zhu,1 Yang-Tai Guan1,2 1Department of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China; 2Department of Neurology, Pu Nan Branch of Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this work Correspondence : Yang-Tai Guan; De-Sheng ZhuDepartment of Neurology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China, Tel +86-13386271865; +86-13564719779, Fax +86-21-68383482, Email yangtaiguan@sina.com; deshengzhu2008@sina.comBackground: The relationship between serum low-density lipoprotein cholesterol (LDL-C) and the risk of relapse in neuromyelitis optica spectrum disorder (NMOSD) remains uncertain. We aimed to examine the association between serum LDL-C level and relapse in NMOSD patients.Methods: We conducted an analysis of the prospective observational NMOSD cohort study with consecutive 184 hospitalized NMOSD patients from department of neurology. Blood samples were collected to measure LDL-C level upon admission. Primary and relapse were evaluated during hospitalization. The relationship between serum LDL-C level and relapse were analyzed by linear curve fitting analyses. Crude and adjusted odds ratios (OR) of LDL-C for relapse with 95% confidence intervals were analyzed using multiple logistic regression models. ROC curve analysis was used to identify the target lipid-lowering value of LDL-C and the probability of relapse was evaluated by the Kaplan–Meier Plot.Results: Over a mean disease course of 100± 87 days, 59.24% (n=109) participants developed relapse with higher LDL-C than the primary group (n=75) (p< 0.001). Adjusted smoothed plots suggested that there were linear relationships between serum LDL-C level and relapse (p< 0.001). The OR (95% CI) between serum LDL-C level and relapse were 2.67 (1.76– 4.04, p< 0.001), and 2.38 (1.48– 3.83, p< 0.001) respectively in NMOSD patients before and after adjusting for potential confounders. The target LDL-C lowering values were 2.795 mmol/L with potential benefits to prevent relapse in NMOSD.Conclusion: In this sample of NMOSD patients, we found that the elevated serum LDL-C was independently and positively associated with the relapse, and serum LDL-C should be well-controlled to prevent the relapse of NMOSD.Keywords: neuromyelitis optica spectrum disorder, NMOSD, low-density lipoprotein cholesterol, relapse, multivariate analysis

Yu-Yun Zheng, Xin-Yi Tong, Da-Ying Zhang, Jian-Ming Ouyang Institute of Biomineralization and Lithiasis Research, College of Chemistry and Materials Science; Jinan University, Guangzhou, 510632, People’s Republic of ChinaCorrespondence: Jian-Ming Ouyang, Email toyjm@jnu.edu.cnObjective: This study aimed to study the effect of selenium modification on the bioactivity of corn silk polysaccharides, particularly its antioxidant and anti-inflammatory functions.Methods: HNO3-NaSeO3 was used to selenize degraded corn silk polysaccharides (DCSP). The structure and physicochemical properties of DCSP and selenized corn silk polysaccharides (Se-DCSP) were characterized by inductively coupled plasma emission spectroscopy, Fourier-transform infrared, ultraviolet–visible spectroscopy, nuclear magnetic resonance, nanometer, scanning electron microscopy, and thermogravimetric analysis. The protective effects of DCSP and Se-DCSP on HK-2 cells damaged by nano-calcium oxalate and the changes of inflammatory factors were detected by laser confocal microscopy, flow cytometry, and fluorescence microscopy.Results: The selenium content of DCSP and Se-DCSP were 19.5 and 1226.7 μg/g, respectively. Compared with DCSP, Se-DCSP showed significantly improved biological activity, including the scavenging ability of various free radicals (increased by about 2– 3 times), the intracellular reactive oxygen content (decreased by about 1.5 times), and the mitochondrial membrane potential (decreased by about 2.5 times). Moreover, cell viability and morphological recovery ability were improved. Compared with DCSP, Se-DCSP significantly down-regulated HK-2 cell inflammatory factors MCP-1 (about 1.7 times), NLRP3, and NO (about 1.5 times).Conclusion: The antioxidant activity and the ability to down-regulate the expression of inflammatory factors of Se-DCSP were significantly enhanced compared with DCSP, and Se-DCSP can better protect HK-2 cells from oxidative damage, indicating that Se-DCSP has a stronger potential ability to inhibit kidney stone formation. Keywords: selenization, corn silk polysaccharide, antioxidant, cell protection, inflammation

Ya-Ya Bai,1 Rui Tian,1 Yan Qian,2 Qiao Zhang,1 Chong-Bo Zhao,1 Yong-Gang Yan,1 Li Zhang,3 Shi-Jun Yue,4 Yu-Ping Tang1 1Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Shaanxi Traditional Chinese Medicine Processing Technology Heritage Base, Shaanxi University of Chinese Medicine, Xi’an, 712046, People’s Republic of China; 2Suzhou Institute for Drug Control, Suzhou, Jiangsu Province, 215000, People’s Republic of China; 3Hanlin College, Nanjing University of Chinese Medicine, Taizhou, Jiangsu Province, 225300, People’s Republic of China; 4International Joint Research Center on Resource Utilization and Quality Evaluation of Traditional Chinese Medicine of Hebei Province, Hebei University of Chinese Medicine, Shijiazhuang, 050200, People’s Republic of ChinaCorrespondence: Qiao Zhang, Shaanxi University of Chinese Medicine, Shiji Avenue, Xi Xian New District, Xi’an, 712046, People’s Republic of China, Tel +86-15895973680, Fax: +86-02938185061, Email 18700081184@163.comBackground: Long-term use of rhubarb (RH) commonly leads to diarrhea, which can be alleviated by steaming with wine. However, the specific mechanism by which wine steaming alleviates RH-induced diarrhea remains unknown.Objective: This study aims to reveal the underlying mechanisms of wine steaming in alleviating RH-induced diarrhea by examining small intestinal flora and serum metabolomics.Methods: Major anthraquinone and anthrone components were detected using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Eighty-four ICR mice were randomly divided into control, RH, and RH steamed with wine (PRH) groups and were administered RH and PRH (1, 4, and 8 g/kg, i.g). for 14 consecutive days. Histopathological analysis was performed using hematoxylin-eosin staining. Levels of inflammatory factors and tight junction proteins, zonula occludens-1 (ZO-1) and occludin, in the small intestine were measured. The small intestine content was analyzed using 16S rRNA sequencing, and UPLC-MS was used to analyze endogenous metabolites.Results: Levels of major anthraquinone and anthrone components decreased in PRH. Both RH and PRH groups showed varying degrees of loose stools and increased fecal water rates; the RH group exhibited more severe effects. Compared with the control group, RH caused small intestine injuries, increased levels of inflammatory cytokines, downregulated the expression of ZO-1 and occludin, and induced gut microbiota (GM) imbalance. The relative abundance of Lactobacillus decreased, while the relative abundance of Shigella and Streptococcus increased. However, PRH had a milder impact than RH. The glycerophospholipid metabolic pathway was involved in this effect. The levels of inflammatory cytokines and potential metabolites (sn-glycero-3-phosphoethanolamine) were positively correlated with Streptococcus infection, while the levels of ZO-1 and occludin were negatively correlated with Streptococcus infection. GM imbalance and abnormal glycerophospholipid metabolism contributed to impaired intestinal barrier function and inflammatory factor release, which may underlie RH-induced diarrhea, though PRH had a weaker effect.Conclusion: PRH alleviated RH-induced diarrhea by recovering GM balance, reducing ZO-1 and occludin expression, and decreasing the release of inflammatory factors. This mechanism may be linked to the reduced anthraquinone content. This study is the first to explore the mechanism of wine steaming in alleviating RH-induced diarrhea through small intestinal flora and serum metabolomics. It provides data to support the broader clinical use of RH and its safer application. Keywords: gut microbiota, metabolomics, wine steaming, diarrhea, rhubarb

Yu-Sen Feng,1,&ast; Zheng-Yun Sun,2,&ast; Fei Jiang,3 Peng-Cheng Ma,1 Xing-Rui Liu,1 Yuan-Yuan Meng,2 Cheng-De Liao,1 Gui-Fang Sun1 1Department of Radiology, Kunming Yan’an Hospital, Kunming, 650051, People’s Republic of China; 2Department of Radiology, Lincang First People’s Hospital, Lincang, 677000, People’s Republic of China; 3Department of Radiology, Wenshan First People’s Hospital, Wenshan, 663599, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gui-Fang Sun, Department of Radiology, Kunming Yan’an Hospital, No. 245 Renmin East Road, Panlong District, Kunming, Yunnan, 650051, People’s Republic of China, Tel +86 13759518529, Email guifang_sun07@126.comObjective: This study aims to evaluate the relationship between the pericoronary fat attenuation index (FAI), derived from coronary artery computed tomography angiography, and post-lipid management levels of low-density lipoprotein cholesterol in patients with coronary artery disease (CAD). Additionally, the study investigates coronary inflammation across different lipid management strategies.Methods: We selected a cohort comprising 521 CAD patients who met the inclusion criteria. Patients were categorized into well-managed (LDL-C< 2.6 mmol/L) and poorly managed (LDL-C≥ 2.6 mmol/L) groups based on lipid management efficacy. We collected anthropometric measures (height, weight, body mass index, and body surface area) and clinical indicators, including Gensini score, and FAI-related parameters for coronary atherosclerotic lesions. We analyzed the interrelations along these parameters and lipid management using statistical methods and assessed diagnostic value via receiver operating characteristic (ROC) curve analysis of these parameters was assessed through.Results: The poorly managed group exhibited significantly higher levels of total cholesterol, triglycerides, and lower levels of high-density lipoprotein compared to the well-managed group (P < 0.05). Significant differences were observed between the groups in terms of lesion length in the proximal segment of the left anterior descending artery, FAI value in the proximal segment of lesions in the right coronary artery (RCA), volume thickness in the middle segment of RCA lesions, and lesion length in the distal segment of RCA (P < 0.05). ROC curve analysis revealed areas under the curve ranging from 0.484 to 0.660 for the parameters, indicating limited diagnostic efficacy.Conclusion: The FAI in the RCA varies with lipid management strategies, suggesting it as a valuable metric for monitoring both perivascular inflammation and lipid status in CAD patients. However, its current diagnostic efficacy is limited, indicating the need for further research to improve its clinical utility.Keywords: coronary artery CT angiography, coronary atherosclerotic heart disease, coronary inflammation, lipids, low-density lipoprotein cholesterol, pericoronary fat attenuation index

Yu-Yan Qin,1,&ast; Hui Yu,1,2,&ast; Yong Huang,1,&ast; Xiaoyi Yang,1 Songpei Li,1 Ao Shen,1 Yinshan Lin,1 Mei Zhang,1 Qiulian Zhu,1 Jingwei Zhang,1 Lingmin Zhang,1 Xi-Yong Yu1 1Key Laboratory of Molecular Target & Clinical Pharmacology and the State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China; 2Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Co., Ltd, Guangzhou, Guangdong, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xi-Yong Yu; Lingmin Zhang, School of Pharmaceutical Sciences, Guangzhou Medical University, Xinzao Road, Panyu District, Guangzhou, 511436, People’s Republic of China, Email yuxycn@gzhmu.edu.cn; zhanglm@gzhmu.edu.cnBackground: Acute lung injury (ALI) leads to diffuse pulmonary interstitial and alveolar edema, further developing into acute respiratory distress syndrome (ARDS). The present therapeutic approaches showed limited effects with poor clinical efficacy or severe side effects. This study aims to develop novel pharmaceutical agents to reduce lung damage with acceptable side effects for ALI.Methods: Naked gene delivery system based on epigallocatechin 3-gallate (EGCG) was synthesized to deliver plasmid expressing DNA damage regulated autophagy modulator 1 (DRAM1), designated as EGCG/DRAM1 (ED). ED was characterized by dynamic light scattering analysis and transmission electron microscope. The biodistribution of ED in mice was measured by an in vivo small animal imaging system. The therapeutic potentials of ED were evaluated in MLE12 cells and LPS-induced ALI mice.Results: Our results showed that ED was nearly spherical with a diameter of ~100 nm and increased the stability of DRAM1 plasmid that encapsulated. The synthesized ED showed negligible toxicity at the selected experimental concentration in MLE12 cells. ED could be taken up by MLE12 cells with high efficiency and escape from the lysosome. In ALI mice, ED facilitated the accumulation and retention of DRAM1 plasmid in lung, and attenuated pulmonary edema and pulmonary vascular permeability. The therapeutic effects of ED on ALI were associated with increased autophagy and reduced oxidative stress in lung.Conclusion: In summary, ED attenuated pulmonary edema and pulmonary vascular permeability, and improved pulmonary dysfunction in ALI mice. This naked gene delivery system for autophagy enhancement may serve as a potential therapeutic strategy to attenuate ALI. Keywords: acute lung injury, EGCG, DRAM1, autophagy, oxidative stress

Xiao-Yang Xu,&ast; Ze Wang,&ast; Chen-You Liu,&ast; Hao-Dong Wu, Ze-Xin Hu, Yu-Ying Lin, Shuai Zhang, Jian Shen, Bin-Yan Zhong, Xiao-Li Zhu Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Li Zhu, Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Street, Suzhou, 215006, People’s Republic of China, Email zhuxiaoli90@163.comObjective: To explore changing trends in circulating immune indicators of hepatocellular carcinoma (HCC) undergoing TACE plus immune checkpoint inhibitors (ICIs) and anti-VEGF antibodies/TKIs and to elucidate the relationship between immune response and tumor prognosis.Materials: This single-center retrospective study included patients with unresectable HCC undergoing TACE plus ICIs and anti-VEGF antibodies/TKIs from March 11, 2019, to February 15, 2024. Peripheral blood samples were collected at baseline and every cycle, from which blood cell counts and immune indicators were analyzed. The primary outcome was the objective response rate (ORR) at the first evaluation. According to the first evaluation based on mRECIST, patients were classified into PD, SD, and OR groups for analysis. Further subgroup analysis was performed on the OR group based on whether experiencing progression after the first evaluation. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The neutrophil-to-lymphocyte ratio (NLR) was measured by the complete blood count. Simple linear regression was employed to examine the dynamic trends.Results: A total of 63 patients were enrolled, with an ORR of 55.6% and a disease control rate (DCR) of 87.3% at the first evaluation. The median overall survival (mOS) was 27.5 months (95% CI: 22.5– 32.5 months). In the OR group (n=35), more active immune responses, expressed in a decrease in CD3−CD19+ (p=0.004), CFB (p=0.027), NLR (p< 0.001) and an increase in Ig λ (p=0.010), Ig κ (p=0.037), Ig A (p=0.005), Ig G (p=0.006), were related to better prognosis, while similar patterns seen in the OR-nPD subgroup. Concurrently, no significant differences were noted in the PD group (n=8).Conclusion: The combination therapy may modify the tumor microenvironment of HCC. Changing trends in circulating immune indicators and NLR can serve as potential biomarkers for predicting tumor response and guiding clinical treatment.Keywords: immune indicator, TACE, immune checkpoint inhibitors, tyrosine kinase inhibitors, tumor microenvironment

Xu-Lin Wang,1,&ast; Ling-Ling Dai,2,&ast; Yan-Na Li,1 Jian-Wen Zhang,1 Ming-Cui Qu,1 Yao-Yao Zhou,1 Na Xing1 1Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Respiration, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Na Xing, Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, People’s Republic of China, Tel +8613949095172, Email 16427485@qq.comPurpose: This study aimed to compare the efficacy of remimazolam and propofol regarding postoperative anesthesia satisfaction in patients undergoing outpatient gynecological surgery.Patients and Methods: This was a single-center, open-label, non-inferiority, randomized clinical trial. Patients aged ≥ 18 years who underwent outpatient gynecological surgery with sedation were enrolled. Participants were randomly assigned to be sedated with remimazolam or propofol. The primary endpoint was the immediate postoperative anesthesia satisfaction score, evaluated through the Iowa Satisfaction with Anesthesia Scale (ISAS).Results: 168 patients were randomly allocated to either the remimazolam group (n = 84) or the propofol group (n = 84). The mean (standard deviation) ISAS scores immediately after surgery were 1.7 (0.6) for the remimazolam group and 2.0 (0.7) for the propofol group (difference, – 0.2; 97.5% confidence interval [CI]: – 0.5 to – 0.0; p = 0.02), indicating non-inferiority. The length of post-anesthesia care unit (PACU) stay was longer in the remimazolam group than in the propofol group (27.6 [9.1] min vs 22.4 [7.0] min; difference, 5.2 [95% CI: 2.7 to 7.6] min; p < 0.001). High-intensity injection pain was less frequently observed in the remimazolam group than in the propofol group (3.6% vs 45.2%; difference, – 41.7% [95% CI: – 54.2% to – 29.1%]; p < 0.001). The nausea score was higher in the remimazolam group immediately after surgery than in the propofol group. Pain, nausea, sleep quality, anxiety, and depression scores were higher in the remimazolam group than in the propofol group on postoperative day 1. The incidence of adverse events and other secondary endpoints was comparable between the two groups.Conclusion: Remimazolam was non-inferior to propofol regarding postoperative anesthesia satisfaction in patients undergoing outpatient gynecological surgery. Therefore, it should be considered as a new sedation alternative in such procedures.Keywords: remimazolam, propofol, patient satisfaction, outpatient gynecological surgery, sedation

Hong-Jing Zhu,1,&ast; Sheng-Yu Zhou,1,&ast; Yang Qu,1 Ying-Ying Sun,1 Ke-Jia Zhang,1 Shu-Yan Pang,1 Yi Yang,1 Zhen-Ni Guo1,2 1Stroke Center, Department of Neurology, The First Hospital of Jilin University, Chang Chun, People’s Republic of China; 2Neuroscience Research Center, Department of Neurology, The First Hospital of Jilin University, Chang Chun, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhen-Ni Guo; Yi Yang, Stroke Center, Department of Neurology, The First Hospital of Jilin University, Xinmin Street 1&num;, Changchun, 130021, People’s Republic of China, Tel +86-18186872986 ; +86-13756661217, Fax +86-431-88782378, Email zhen1ni2@163.com; yang_yi@jlu.edu.cnPurpose: Although recombinant tissue plasminogen activator (rt-PA) treatment is efficient in patients with acute ischemic stroke (AIS), a significant percentage of patients who received rt-PA intravenous thrombolysis (IVT) do not achieve a good prognosis. Therefore, the factors that affect the poor prognosis of patients with IVT are needed. The Fibrosis-4 (FIB-4) index has been used as a liver fibrosis biomarker. We aimed to investigate the relationship between the FIB-4 index and functional outcomes in patients with AIS receiving IVT.Patients and Methods: This study prospectively included consecutive patients with AIS receiving IVT between April 2015 and May 2022. We collected clinical and laboratory data and calculated the FIB-4 index. Clinical outcome was poor functional outcome (mRS ≥ 3) at 3 months after IVT. Multivariate logistic regression analysis was used to analyze the association between FIB-4 and outcome. We explored the interactive effect of FIB-4 and dyslipidemia on poor outcomes, and subgroup analysis was performed. Furthermore, an individualized prediction model based on the FIB-4 for functional outcome was established in the dyslipidemia group.Results: A total of 1135 patients were included, and 41.50% had poor 3-month outcomes. After adjusted by other variants that P value < 0.05 in univariable analysis, FIB-4 was independently associated with poor outcomes (OR=1.420; 95% CI: 1.113– 1.812; P=0.004). There was a significant interaction between FIB-4 and dyslipidemia on poor outcome (P=0.036), and the independent association between FIB-4 and poor outcome was maintained in the dyslipidemia subgroup (OR=1.646; 95% CI: 1.228– 2.206; P=0.001). Furthermore, in the dyslipidemia group, the FIB-4-based prediction model had good predictive value (the AUC of the training and validation sets were 0.767 and 0.708, respectively), good calibration (P-values for the Hosmer–Lemeshow test > 0.05), and clinical usefulness.Conclusion: FIB-4 is an independent risk factor for poor outcomes in IVT patients with dyslipidemia, which can be used as a simple predictor of their prognosis.Keywords: Fibrosis-4, acute ischemic stroke, intravenous thrombolysis, prognosis, dyslipidemia

Fu-Xing-Zi Li,1 Feng Xu,1 Chang-Chun Li,1 Li-Min Lei,1 Su-Kang Shan,1 Ming-Hui Zheng,1 Xiao Lin,2 Bei Guo,1 Ke-Xin Tang,1 Jia-Yue Duan,1 Yun-Yun Wu,1 Ye-Chi Cao,1 Jun-Jie Liu,3 Ling-Qing Yuan1 1Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 3Department of Periodontal Division, Hunan Xiangya Stomatological Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of ChinaCorrespondence: Ling-Qing Yuan, Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Email allenylq@csu.edu.cnPurpose: Anecdotal reports have praised the benefits of cold exposure, exemplified by activities like winter swimming and cold water immersion. Cold exposure has garnered acclaim for its potential to confer benefits and potentially alleviate diabetes. We posited that systemic cold temperature (CT, 4– 8°C) likely influences the organism’s blood components through ambient temperature, prompting our investigation into the effects of chronic cold exposure on type 2 diabetic (T2DM) mice and our initial exploration of how cold exposure mitigates the incidence of T2DM.Methods: The effects of CT (4– 8°C) or room temperature (RT, 22– 25°C) on T2DM mice were investigated. Mice blood and organ specimens were collected for fully automated biochemical testing, ELISA, HE staining, immunohistochemistry, and immunofluorescence. Glucose uptake was assessed using flow cytometry with 2-NBDG. Changes in potential signaling pathways such as protein kinase B (AKT), phosphorylated AKT (p-AKT), insulin receptor substrates 1 (IRS1), and phosphorylated IRS1 (p-IRS1) were evaluated by Western blot.Results: CT or CT mice plasma-derived extracellular vesicles (CT-EVs) remarkably reduced blood glucose levels and improved insulin sensitivity in T2DM mice. This treatment enhanced glucose metabolism, systemic insulin sensitivity, and insulin secretion function while promoting glycogen accumulation in the liver and muscle. Additionally, CT-EVs treatment protected against the streptozocin (STZ)-induced destruction of islets in T2DM mice by inhibiting β-cell apoptosis. CT-EVs also shielded islets from destruction and increased the expression of p-IRS1 and p-AKT in adipocytes and hepatocytes. In vitro experiments further confirmed its pro-insulin sensitivity effect.Conclusion: Our data indicate that cold exposure may have a potentially beneficial effect on the development of T2DM, mainly through the anti-diabetic effect of plasma-derived EVs released during cold stimulation. This phenomenon could significantly contribute to understanding the lower prevalence of diabetes in colder regions.Keywords: cold exposure, plasma-derived extracellular vesicles, type 2 diabetes, insulin sensitivity, β‑cell destruction

Yong-Yao Wu,1,&ast; Jun-Yuan Li,1,&ast; Qiao-Jing Xia,1 Yi-Yi Gao,1 Chao Zhang,1 Peng-Jie Xu,1 Jiang Liu,1 Hao-Jie Zhang,1 Ri-Zhen Yu2 1Department of Nephrology, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang Province, 315099, People’s Republic of China; 2Urology & Nephrology Center, Department of Nephrology, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang Province, 310014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao-Jie Zhang, Department of Nephrology, Ningbo Medical Center Lihuili Hospital, No. 1111 Jiangnan Road, Yinzhou District, Ningbo City, Zhejiang Province, 315099, People’s Republic of China, Email zhang_haojie843@outlook.com Ri-Zhen Yu, Urology & Nephrology Center, Department of Nephrology, Affiliated People’s Hospital, Hangzhou Medical College, No. 158 Shangtang Road, Gongshu District, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86 571-85893889, Fax +86 571-85131448, Email rizhen_3180yu83@126.comObjective: Sarcopenia is more common in maintenance hemodialysis (MHD) patients, and the aim of this study is to analyze the risk factors associated with sarcopenia in MHD patients, along with its correlation to emotional status and quality of life.Methods: This is a cross-sectional cohort study. A total of 111 MHD patients who were treated in the Department of Nephrology of our hospital were selected as the study subjects by convenience sampling. The quality of life and emotional status were evaluated by health survey scale (SF-36), self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Regression analysis was used to explore the influencing factors of sarcopenia. Correlation analysis was used to investigate the correlation between sarcopenia and quality of life and emotional status.Results: The prevalence of sarcopenia was 59.8%. The results showed that age, gender, body mass index (BMI), dialysis time, economic status, marital status and pre-dialysis creatinine were significant factors affecting the development of sarcopenia in hemodialysis patients (p< 0.05). The SF-36 total score was significantly lower in the sarcopenia group (72.05± 12.28 vs 78.03± 10.55) than in the non-sarcopenia group, but the anxiety scale score (52.97± 4.67 vs 36.2± 3.36) and depression scale score (57.67± 4.58 vs 38.71± 3.77) were significantly higher than those in the non-sarcopenia group (p< 0.001). Correlation analysis showed that sarcopenia was positively correlated with SAS and SDS scores and negatively correlated with SF-36 total score (p < 0.05).Conclusion: The risk of sarcopenia was higher among MHD patients who were older, male, single, with a longer MHD duration, lower economic status, lower BMI, comorbid diabetes and lower levels of creatinine.Keywords: maintenance hemodialysis, sarcopenia, quality of life, risk factors, cross-sectional studies

Luo-Gang Ding,1,&ast; Xiang Ji,2,&ast; Yue-Yue Liu,3,&ast; Min Shi,1 Jian-Da Li,1 Fei Liu,1 Yu-Yu Zhang,1 Jiang Yu,1 Jia-Qiang Wu1 1Shandong Key Laboratory of Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, 250100, People’s Republic of China; 2Key Laboratory of Shandong Microbial Engineering, College of Bioengineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, People’s Republic of China; 3Institute of Poultry Science, Shandong Academy of Agricultural Science, Jinan, 250100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jia-Qiang Wu; Jiang Yu, Shandong Academy of Agricultural Sciences, Jinan, 250100, People’s Republic of China, Email yujiang_2213@163.com; wujiaqiang2000@sina.comBackground: Influenza A (H1N1) virus is a highly contagious respiratory disease that causes severe illness and death. Vaccines and antiviral drugs are limited by viral variation and drug resistance, so developing efficient integrated theranostic options appears significant in anti-influenza virus infection.Methods: In this study, we designed and fabricated covalent organic framework (COF) based theranostic platforms (T705@DATA-COF-Pro), which was composed of an RNA polymerase inhibitor (favipiravir, T705), the carboxyl-enriched COF (DATA-COF) nano-carrier and Cy3-labeled single DNA (ssDNA) probe.Results: The multi-porosity COF core provided an excellent micro-environment and smooth delivery for T705. The ssDNA probe coating bound to the nucleic acids of H1N1 selectively, thus controlling drug release and allowing fluorescence imaging. The combination of COF and probe triggered the synergism, promoting drug further therapeutic outcomes. With the aid of T705@DATA-COF-Pro platforms, the H1N1-infected mouse models lightly achieved diagnosis and significantly prolonged survival.Conclusion: This research underscores the distinctive benefits and immense potential of COF materials in nano-preparations for virus infection, offering novel avenues for the detection and treatment of H1N1 virus infection.Keywords: crystal porous materials, microenvironment-responsive, controlled release, fluorescence imaging, diagnosis and therapy

Abstract Background Ceramides have recently been identified as novel biomarkers associated with diabetes mellitus (DM) and major adverse cardiac and cerebrovascular events (MACCE). This study aims to explore their utility in diagnosing microvascular disease. Methods This study prospectively enrolled 309 patients from 2018 to 2020 into three groups: healthy controls (Group 1, N = 51), DM patients without acute myocardial infarction (AMI) (Group 2, N = 150), and DM patients with AMI (Group 3, N = 108). We assessed outcomes using stress perfusion cardiac magnetic resonance (CMR) imaging for coronary microvascular disease (CMD) (Outcome 1), retinography for retinal microvascular disease (RMD) (Outcome 2), both CMD and RMD (Outcome 3), and absence of microvascular disease (w/o MD) (outcome 4). We evaluated the classification performance of ceramides using receiver operating characteristic (ROC) analysis and multiple logistic regression. 11-ceramide panel previously identified by our research group as related to macrovascular disease were used. Results Average glycated hemoglobin (HbA1c) values were 5.1% in Group 1, 8.3% in Group 2, and 7.6% in Group 3. Within the cohort, CMD was present in 59.5% of patients, RMD in 25.8%, both CMD and RMD in 18.8%, and w/o MD in 38.5%. The AUC values for the reference ceramide ratios were as follows: CMD at 0.66 (p = 0.012), RMD at 0.61 (p = 0.248), CMD & RMD at 0.64 (p = 0.282), and w/o MD at 0.67 (p = 0.010). In contrast, the AUC values using 11-ceramide panel showed significant improvement in the outcomes prediction: CMD at 0.81 (p = 0.001), RMD at 0.73 (p = 0.010), CMD & RMD at 0.73 (p = 0.04), and w/o MD at 0.83 (p = 0.010). Additionally, the plasma concentration of C14.0 was notably higher in the w/o MD group (p

Xiao-Yan He,1 Wen-Yan Tan,2 Li-Li Guo,1 Ying-Ying Ji,1 Fu-Jun Jia,2 Shi-Bin Wang2,3 1The Affiliated Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, Jiangsu Province, People’s Republic of China; 2Guangdong Mental Health Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 3School of Health, Zhuhai College of Science and Technology, Zhuhai, Guangdong Province, People’s Republic of ChinaCorrespondence: Ying-Ying Ji, 5/F. The Affiliated Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Jiangsu Province, People’s Republic of China, Tel +86-510-83290034, Fax +86-510-83012698, Email yingying@jiangnan.edu.cn Shi-Bin Wang, 3/F, Guangdong Mental Health Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China, Tel +86-20-81888553, Fax +86-20-8188-2664, Email spiriorwang@126.comPurpose: The study aims to understanding the mental health literacy level of urban and rural residents in Guangdong Province, the first major province in China, and its influencing factors is crucial.Methods: A multi-stage stratified equal-volume random sampling method was adopted in October-December 2022 to select permanent residents aged 18 years and above in Guangdong Province for the questionnaire survey, which consisted of a general demographic information questionnaire and a national mental health literacy questionnaire. Rao-Scott χ²-test with correction based on sampling design, independent samples t-test and binary multivariate logistic regression analysis were performed.Results: A total of 51744 individuals completed the questionnaire, including 31822 urban residents and 19200 rural residents. The rate of achievement of mental health literacy was 13.6% among urban residents, which was significantly higher compared to the rate of 8.6% among rural residents. Logistic regression analysis showed that female, higher education, being mental worker, being a retiree, having a higher monthly household income, maintaining a regular diet, and using electronic products for 2– 6 hours per day were protective factors for mental health literacy attainment in urban residents, while having chronic diseases, being a smoker and having a history of drinking were identified as risk factors in urban residents. Among in rural residents, married, younger, higher education, being mental worker and using electronic products for 2– 6 hours per day, maintaining a regular diet, and engaging in regular exercise were protective factors for achieving mental health literacy, while previous smoking was a risk factor.Conclusion: The study revealed a low level of mental health literacy among urban and rural residents of Guangdong Province, with a significant disparity between the two areas. These findings highlight the need for continuing efforts to increase the dissemination of mental health knowledge in rural communities and improve levels of mental health literacy.Keywords: mental health literacy, urban and rural residents, cross-sectional studies

Fang Fang,1,&ast; Yun Yan Chen,1,&ast; Xin-Ming Zhang,2 Jin Tang,1 Yu-Hao Liu,1 Chen-Shuo Peng,1 Yu Sun1,3 1School of Pharmacy, Wannan Medical College, Wuhu, 241002, People’s Republic of China; 2School of Chemistry and Materials Science, Anhui Normal University, Wuhu, 241002, People’s Republic of China; 3Institute of Synthesis and Application of Medical Materials, Wannan Medical College, Wuhu, 241002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Sun, School of Pharmacy, Wannan Medical College, Wuhu, 241002, People’s Republic of China, Tel +86 553 3932026, Email whsunyu@163.comBackground: Epidermal growth factor receptor (EGFR) is a major target for the treatment of colorectal cancer. Thus, anti-EGFR antibody conjugated lipid-polymer hybrid nanoparticles can offer a potential means of enhancing the efficacy of chemotherapeutics in EGFR overexpressing cancers. In addition, the combination of chemotherapy and photothermal therapy is a promising strategy for cancer treatment. Hence, it is highly desirable to develop a safe and effective delivery system for colorectal tumor therapy.Methods: In this study, EGFR-targeted and NIR-triggered lipid-polymer hybrid nanoparticles (abbreviated as Cet-Iri-NPs) were prepared with copolymer PPG-PEG, lipids DSPE-PEG-Mal and lecithin as carriers, CPT-11 as an anticancer chemotherapeutic agent, indocyanine green (ICG) as a photothermal agent, and cetuximab as a surface-targeting ligand.Results: In vitro analyses revealed that Cet-Iri-NPs were spherical with size of 99.88 nm, charge of 29.17 mV, drug entrapment efficiency of 51.72%, and antibody conjugation efficiency of 41.70%. Meanwhile, Cet-Iri-NPs exhibited a remarkable photothermal effect, and pH/NIR-triggered faster release of CPT-11 with near infrared (NIR) laser irradiation, which induced enhanced cytotoxicity against SW480 cells. Furthermore, the promoted tumor-growth suppression effect of Cet-Iri-NPs on SW480 tumor xenograft nude mice was achieved under NIR laser irradiation.Conclusion: These results indicate that the well-defined Cet-Iri-NPs are a promising platform for targeted colorectal cancer treatment with chemo-photothermal therapy. Keywords: Chemo-photothermal therapy, Targeted cancer therapy, Nanoparticles, Cetuximab, Indocyanine green

Aihaidan Abudouwayiti, Sureya Yisimayili, Ruzeguli Tuersun, Salamaiti Aimaier, Didaer Yisha, Xing Yan Zhang, Ying-Ying Zheng,&ast; Ailiman Mahemuti&ast; The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying-Ying Zheng; Ailiman Mahemuti, Cardiovascular Department of The First Affiliated Hospital of Xinjiang Medical University, 137 Carp Road, Xinshi District, Urumqi, 830054, Xinjiang, People’s Republic of China, Tel +86-15214804944 ; +86-13639970300, Email zhengying527@163.com; xinjiangailiman@163.comBackground: The role of high-density lipoprotein cholesterol (HDL-C) in heart failure (HF) outcomes is contentious. We aimed to assess HDL-C’s prognostic value in HF patients.Methods: In this retrospective cohort study (2012– 2022) at the First Affiliated Hospital of Xinjiang Medical University, we analyzed 4442 patients, categorized by HDL-C quartiles. We applied the Cox proportional hazards model to assess survival and report hazard ratios (HR) with 95% confidence intervals (CI).Results: Over a decade, we recorded 1354 fatalities (42.3%) and 820 readmissions. The third HDL-C quartile (0.93– 1.14 mmol/L) showed the lowest mortality rates, with reduced risks in the second and third quartiles compared to the first (Q2 HR=0.809, 95% CI 0.590– 1.109; Q3 HR=0.794, 95% CI 0.564– 1.118). The fourth quartile presented a lower mortality risk compared to the first (Q4 HR=0.887, 95% CI 0.693– 1.134). A significant correlation existed between HDL-C levels and cardiovascular risk (HR=0.85, 95% CI 0.75– 0.96, p< 0.01).Conclusion: HDL-C levels exhibit a complex association with mortality in HF, indicating the importance of HDL-C in HF prognosis and the need for tailored management strategies.Keywords: high-density lipoprotein cholesterol, heart failure, death, readmission, cardiovascular disease

Yi-yang Sun, Peng-fei Wang, Gui-rong Yang, Dong-qing Du, Chun-jing Li, Zi-jun Mu, Yu-xia Ma, Na Zhang Department of Acupuncture-Moxibustion and Tuina, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of ChinaCorrespondence: Yu-xia Ma; Na Zhang, Email phdmayuxia@126.com; zhangna2008zhentui@163.comBackground: Clinical acupuncture decisions are highly operator-dependent and require physician-patient interactions. The Delphi method allows subjective factors such as expert experience and preference of patients to be taken into account in clinical decision making, which is particularly applicable to acupuncture. Currently, the Delphi method is widely used to support clinical decisions in acupuncture. Therefore, it is necessary to provide high-quality and complete descriptions of the Delphi process when making clinical decisions. This study aims to evaluate the quality of the Delphi process in acupuncture, facilitate its standardization and rigor for further clinical decision making in acupuncture.Methods: Articles sourced from six databases were searched systematically to assess the quality of the Delphi consensus process based on the standards for conducting and reporting Delphi studies (CREDES). Descriptive statistics and analysis were presented according to the percentage of each item. Five-score Likert scale was used to evaluate the reporting quality of four domains as well as each item in CREDES by two independent researchers, combined with ICC-value to assess the consistency.Results: A total of 37 qualified articles were included according to eligibility criteria. As for the low reporting rate, the item “External validation” was reported as the lowest positive rate at 32.43% and the item “Prevention of bias” was 48.65%. The item “Adequacy of conclusions”, “Definition and attainment of consensus”, and “Discussion of limitations” were reported at a positive ratio of 62.16%, 64.86%, and 67.57% individually. The average scores of the four domains based on CREDES from highest to lowest were, respectively, as follows: planning and design (68.75%), reporting (66.07%), rationale for the choice of the Delphi technique (65.54%), study conduct (45.10%).Conclusion: The reporting quality of the Delphi consensus process in acupuncture is acceptable currently, but the reporting rate on some items is still low. Further standardization, including either clearer checklists or study reports, should be developed and strengthened to guide clinical decisions in acupuncture.Keywords: delphi, consensus, acupuncture, CREDES, quality assessment

Yu-Pei Wang,1,&ast; Hui-Xia Wei,2,&ast; Yuan-Yuan Hu,3 Yu-Ming Niu3,4 1Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, People’s Republic of China; 2Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, People’s Republic of China; 3Department of Stomatology, Gongli Hospital of Shanghai Pudong New Area, Shanghai, People’s Republic of China; 4Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei Provincial Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem Cells, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu-Ming Niu, Department of Stomatology, Gongli Hospital of Shanghai Pudong New Area, Shanghai, People’s Republic of China, Tel: +86 13581370999, Email niuyuming@yeah.netObjective: This study was conducted to investigate the bidirectional causal relationship between obstructive sleep apnea (OSA) and temporomandibular disorders (TMD).Methods: Using an online pooled dataset of genome-wide association studies (GWAS), a two-sample bi-directional Mendelian randomization (MR) method was implemented. Inverse variance weighting was used as the primary analyses approach, and other methods of MR Egger, weighted median method, MR-Egger, Simple mode, and Weighted mode analysis were conducted as supplements to evaluate the causal relationship between OSA and TMD with odds ratios (OR) and 95% confidence interval (CI). Furthermore, the Cochran Q, MR-Egger, and MR-PRESSO approaches were used to perform the heterogeneity test and multiple validity.Results: The general results of the forward MR analysis indicated that OSA had a significant causal influence on TMD (OR=1.241, 95% CI: 1.009– 1.526, P=0.041), but no significant correlation was observed in the reverse MR analysis (IVW: OR=0.975, 95% CI=0.918– 1.036, P=0.411).Conclusion: In summary, our research demonstrated a hereditary causative relationship between OSA and TMD, indicating that appropriate intervention is required for both prevention and treatment of TMD.Keywords: Mendelian randomization analysis, obstructive sleep apnea, temporomandibular disorders

Xian-Ping Yang,1,&ast; Ying-Yao Liu,2,&ast; Cai-Yun Zhang,3 Kai-Kai Huang,1 Shan-Shan Han,1 Bao-Ying Liang,1 Ying Lin1 1Department of Dermatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong, People’s Republic of China; 2The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Department of Dermatology, Dongguan Traditional Chinese Medicine Hospital, Dongguan, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Lin, Department of Dermatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), No. 111 Dade Road, Guangzhou, Guangdong, 510120, People’s Republic of China, Email lin19791226@gzucm.edu.cnAim: Atopic dermatitis (AD) often accompanies skin infections, and bacterial skin infections often cause persistent and worsening symptoms. In this study, we explored the key changes in the microbiota of AD patients, as well as the effects of different ages and the severity of rash on changes in the microbiota.Patients and Methods: A total of 95 AD patients and 77 healthy volunteers were recruited. The AD patients were divided into three groups based age and three groups according to the EASI score. Microorganisms collected from the skin were analyzed through 16S rRNA gene sequencing, revealing species diversity via α and β diversity analyses. Species compositions were compared at the phylum and genus levels. The significance of skin microbiota at the genus level was assessed using the random forest algorithm. Finally, the impact of relationships between different microbial communities on the microbial community composition and the pathogenesis of AD was explored using Pearson correlation coefficients.Results: The species diversity of the skin microbiota in the AD group significantly decreased. Compared with that in the healthy volunteers (HV) group, the bacterial diversity in the two groups of samples significantly differed. Staphylococcus dominated the bacterial communities, and as AD symptoms gradually worsened, the abundance of Staphylococcus gradually increased. Among all bacterial genera with a relative abundance greater than 1%, Staphylococcus showed a negative correlation with other genera, and showed significant consistency in specimens from different age groups.Conclusion: Changes in the abundance of Staphylococcus in the skin bacterial colonies are the main cause of AD. Brevundimonas, Paracoccus, Corynebacterium, and Veillonella may serve as characteristic biomarkers for AD. These results indicate that altering the microbiota composition of the skin may aid in the treatment of AD.Keywords: atopic dermatitis, skin bacterial colony, 16S rRNA gene sequencing

Jia-Wen Xie,1,2 Yin-Feng Guo,1,2 Ya-Wen Zheng,1,3 Mao Wang,1,2 Qiu-Yan Xu,1,2 Yu-Yan Chen,1,2 Li-Rong Lin1,2,4 1Center of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 2Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 3Prenatal Diagnosis Center, Zhangzhou Municipal Hospital Affiliated to Fujian Medical University, Zhangzhou, People’s Republic of China; 4Department of Basic Medical Science, Xiamen Medical College, Xiamen, People’s Republic of ChinaCorrespondence: Yu-Yan Chen; Li-Rong Lin, Centre of Clinical Laboratory, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, 361004, People’s Republic of China, Tel +86-592-2993041, Fax +86-592-2993043, Email chenyuyan@xmu.edu.cn; linlirong@xmu.edu.cnPurpose: Accurate differentiation between early and late latent syphilis stages is pivotal for patient management and treatment strategies. Nontreponemal IgM antibodies have shown potential in discriminating latent syphilis staging by differentiating syphilis activity. This study aimed to develop a predictive nomogram model for latent syphilis staging based on nontreponemal IgM antibodies.Patients and Methods: We explored the correlation between nontreponemal IgM antibodies and latent syphilis staging and developed a nomogram model to predict latent syphilis staging based on 352 latent syphilis patients. Model performance was assessed using AUC, calibration curve, Hosmer–Lemeshow χ 2 statistics, C-index, Brier score, decision curve analysis, and clinical impact curve. Additionally, an external validation set was used to further assess the model’s stability.Results: Nontreponemal IgM antibodies correlated with latent syphilis staging. The constructed model demonstrated a strong discriminative capability with an AUC of 0.743. The calibration curve displayed a strong fit, key statistics including Hosmer–Lemeshow χ² at 2.440 (P=0.486), a C-index score of 0.743, and a Brier score of 0.054, all suggesting favorable model calibration performance. Decision curve analysis and clinical impact curve highlighted the model’s robust clinical applicability. The external validation set yielded an AUC of 0.776, Hosmer–Lemeshow χ² statistics of 2.440 (P=0.486), a C-index score of 0.767, and a Brier score of 0.054, further underscored the reliability of the model.Conclusion: The nontreponemal IgM antibody-based predicted model could equip clinicians with a valuable tool for the precise staging of latent syphilis and enhancing clinical decision-making.Keywords: syphilis, latent syphilis, latent syphilis staging, nontreponemal IgM antibody, predictive model

Malarmugila Manimaran,1,&ast; Yin Yin Teo,2 James Chen Yong Kah,3 Adilet Beishenaliev,1 Yean Leng Loke,2 Yiing Yee Foo,1 Shiow-Fern Ng,4 Chin Fei Chee,5 Sek Peng Chin,6 Farid Nazer Faruqu,1 Chia-Yu Chang,7 Misni Misran,2 Lip Yong Chung,6 Bey Fen Leo,8,&ast; Shih-Hwa Chiou,9,10 Chia-Ching Chang,7,11– 13 Sun Tee Tay,14 Lik Voon Kiew1,7 1Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; 2Department of Chemistry, Faculty of Science, Universiti Malaya, Kuala Lumpur, Malaysia; 3Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, Singapore; 4Centre for Drug Delivery Technology and Vaccine, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 5Nanotechnology Catalysis Research Centre, Universiti Malaya, Kuala Lumpur, Malaysia; 6Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur, Malaysia; 7Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 8Department of Molecular Medicine, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia; 9Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China; 10Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan, Republic of China; 11Department of Electrophysics, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 12Center for Intelligent Drug Systems and Smart Bio-devices, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China; 13Institute of Physics, Academia Sinica, Nankang, Taipei, Taiwan, Republic of China; 14Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia&ast;These authors contributed equally to this workCorrespondence: Chia-Ching Chang; Lik Voon Kiew, Email ccchang01@nycu.edu.tw; lvkiew@um.edu.myIntroduction: Over 75% of clinical microbiological infections are caused by bacterial biofilms that grow on wounds or implantable medical devices. This work describes the development of a new poly(diallyldimethylammonium chloride) (PDADMAC)/alginate-coated gold nanorod (GNR/Alg/PDADMAC) that effectively disintegrates the biofilms of Staphylococcus aureus (S. aureus), a prominent pathogen responsible for hospital-acquired infections.Methods: GNR was synthesised via seed-mediated growth method, and the resulting nanoparticles were coated first with Alg and then PDADMAC. FTIR, zeta potential, transmission electron microscopy, and UV–Vis spectrophotometry analysis were performed to characterise the nanoparticles. The efficacy and speed of the non-coated GNR and GNR/Alg/PDADMAC in disintegrating S. aureus-preformed biofilms, as well as their in vitro biocompatibility (L929 murine fibroblast) were then studied.Results: The synthesised GNR/Alg/PDADMAC (mean length: 55.71 ± 1.15 nm, mean width: 23.70 ± 1.13 nm, aspect ratio: 2.35) was biocompatible and potent in eradicating preformed biofilms of methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) when compared to triclosan, an antiseptic used for disinfecting S. aureus colonisation on abiotic surfaces in the hospital. The minimum biofilm eradication concentrations of GNR/Alg/PDADMAC (MBEC50 for MRSA biofilm = 0.029 nM; MBEC50 for MSSA biofilm = 0.032 nM) were significantly lower than those of triclosan (MBEC50 for MRSA biofilm = 10,784 nM; MBEC50 for MRSA biofilm 5967 nM). Moreover, GNR/Alg/PDADMAC was effective in eradicating 50% of MRSA and MSSA biofilms within 17 min when used at a low concentration (0.15 nM), similar to triclosan at a much higher concentration (50 μM). Disintegration of MRSA and MSSA biofilms was confirmed by field emission scanning electron microscopy and confocal laser scanning microscopy.Conclusion: These findings support the potential application of GNR/Alg/PDADMAC as an alternative agent to conventional antiseptics and antibiotics for the eradication of medically important MRSA and MSSA biofilms.Keywords: biofilm, gold nanorod, S. aureus, PDADMAC, MRSA, MSSA

IntroductionTo characterize early-gestation changes in placental structure, perfusion, and oxygenation in the context of ischemic placental disease (IPD) as a composite outcome and in individual sub-groups.MethodsIn a single-center prospective cohort study, 199 women were recruited from antenatal clinics between February 2017 and February 2019. Maternal magnetic resonance imaging (MRI) studies of the placenta were temporally conducted at two timepoints: 14-16 weeks gestational age (GA) and 19-24 weeks GA. The pregnancy was monitored via four additional study visits, including at delivery. Placental volume, perfusion, and oxygenation were assessed at both MRI timepoints. The primary outcome was defined as pregnancy complicated by IPD, with group assignment confirmed after delivery.ResultsIn early gestation, mothers with IPD who subsequently developed fetal growth restriction (FGR) and/or delivered small-for gestational age (SGA) infants showed significantly decreased MRI indices of placental volume, perfusion, and oxygenation compared to controls. The prediction of FGR or SGA by multiple logistic regression using placental volume, perfusion, and oxygenation revealed receiver operator characteristic curves with areas under the curve of 0.81 (Positive predictive value (PPV) = 0.84, negative predictive value (NPV) = 0.75) at 14-16 weeks GA and 0.66 (PPV = 0.78, NPV = 0.60) at 19-24 weeks GA.DiscussionMRI indices showing decreased placental volume, perfusion and oxygenation in early pregnancy were associated with subsequent onset of IPD, with the greatest deviation evident in subjects with FGR and/or SGA. These early-gestation MRI changes may be predictive of the subsequent development of FGR and/or SGA.

Reactor neutrino experiments play a crucial role in advancing our knowledge of neutrinos. In this Letter, the evolution of the flux and spectrum as a function of the reactor isotopic content is reported in terms of the inverse-beta-decay yield at Daya Bay with 1958 days of data and improved systematic uncertainties. These measurements are compared with two signature model predictions: the Huber-Mueller model based on the conversion method and the SM2018 model based on the summation method. The measured average flux and spectrum, as well as the flux evolution with the ^{239}Pu isotopic fraction, are inconsistent with the predictions of the Huber-Mueller model. In contrast, the SM2018 model is shown to agree with the average flux and its evolution but fails to describe the energy spectrum. Altering the predicted inverse-beta-decay spectrum from ^{239}Pu fission does not improve the agreement with the measurement for either model. The models can be brought into better agreement with the measurements if either the predicted spectrum due to ^{235}U fission is changed or the predicted ^{235}U, ^{238}U, ^{239}Pu, and ^{241}Pu spectra are changed in equal measure.

We present a new determination of the smallest neutrino mixing angle θ_{13} and the mass-squared difference Δm_{32}^{2} using a final sample of 5.55×10^{6} inverse beta-decay (IBD) candidates with the final-state neutron captured on gadolinium. This sample is selected from the complete dataset obtained by the Daya Bay reactor neutrino experiment in 3158 days of operation. Compared to the previous Daya Bay results, selection of IBD candidates has been optimized, energy calibration refined, and treatment of backgrounds further improved. The resulting oscillation parameters are sin^{2}2θ_{13}=0.0851±0.0024, Δm_{32}^{2}=(2.466±0.060)×10^{-3}  eV^{2} for the normal mass ordering or Δm_{32}^{2}=-(2.571±0.060)×10^{-3}  eV^{2} for the inverted mass ordering.

Di-Fei Duan,1,2,&ast; Min Liu,1,2,&ast; Deng-Yan Ma,1,2 Lin-Jia Yan,3 Yue-Yang Huang,1,2 Yi Chen,1,2 Wei Jiang,1,2 Xi Tang,2 An-Qi Xiong,4,5 Yun-Ying Shi2 1West China School of Nursing, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 3The Nethersole School of Nursing Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 4Department of Nursing, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 5Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Deng-Yan Ma, Email mdy5104@163.comPurpose: The research on symptom management in patients with diabetic kidney disease (DKD) has shifted from separate symptoms to symptom clusters and networks recently. This study aimed to evaluate the unpleasant symptoms of DKD patients, and to investigate how these symptom clusters could affect patients.Methods: 408 DKD patients were recruited in this cross-sectional study. The symptoms of DKD patients were measured using the modified Dialysis Symptom Index. Network analysis was employed to evaluate the symptom network and the characteristics of individual nodes, while factor analysis was utilized to identify symptom clusters.Results: Blurred vision was the most prevalent symptom among DKD patients. The symptoms identified as the most distressing, severe, and frequent were light headache or dizziness, arteriovenous fistula/catheterization pain, and diarrhea, respectively. Five symptom clusters were obtained from factor analysis, and the most central symptom cluster in the entire symptom network was sexual dysfunction.Conclusion: This study identified five symptom clusters in Chinese DKD patients, with sexual dysfunction emerging as the most central cluster. These findings carry significant clinical implications, underscoring the necessity of assessing symptom clusters and their associations to enhance symptom management in DKD patients. Further research is essential to elucidate the underlying mechanisms of symptoms and to clarify the associations among symptoms in DKD patients across different disease trajectories or treatment modalities.Keywords: diabetic kidney disease, network analysis, symptom cluster, symptom management

Xi-Ding Yang,1,2 Yong-Yu Yang1,3 1Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2Phase I Clinical Trial Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 3Hunan Provincial Engineering Research Central of Translational Medical and Innovative Drug, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Yong-Yu Yang, Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China, Email yongyuyang@csu.edu.cnPurpose: The aim of this review was to provide all the pharmacokinetic data for semaglutide in humans concerning its pharmacokinetics after subcutaneously and oral applications in healthy and diseased populations, to provide recommendations for clinical use.Methodology: The PubMed and Embase databases were searched to screen studies associated with the pharmacokinetics of semaglutide. The pharmacokinetic parameters included area under the curve plasma concentrations (AUC), maximal plasma concentration (Cmax), time to Cmax, half-life (t1/2), and clearance. The systematic literature search retrieved 17 articles including data on pharmacokinetic profiles after subcutaneously and oral applications of semaglutide, and at least one of the above pharmacokinetic parameter was reported in all included studies.Results: Semaglutide has a predictable pharmacokinetic profile with a long t1/2 that allows for once-weekly subcutaneous administration. The AUC and Cmax of both oral and subcutaneous semaglutide increased with dose. Food and various dosing conditions including water volume and dosing schedules can affect the oral semaglutide exposure. There are limited drug–drug interactions and no dosing adjustments in patients with upper gastrointestinal disease, renal impairment or hepatic impairment. Body weight may affect semaglutide exposure, but further studies are needed to confirm this.Conclusion: This review encompasses all the pharmacokinetic data for subcutaneous and oral semaglutide in both healthy and diseased participants. The existing pharmacokinetic data can assist in developing and evaluating pharmacokinetic models of semaglutide and will help clinicians predict semaglutide dosages. In addition, it can also help optimize future clinical trials.Keywords: Pharmacokinetics, semaglutide, curve plasma concentrations, type 2 diabetes, obesity, glucagon-like peptide-1, drug–drug interaction

Xiao-Bei Si,1,2 Ling-Yun Zhang,2 Shuo Yang,3 Xiao-Lu Chen,2 Yan-Yan Shi,4 Yu Lan,2 Shi-Gang Ding1 1Department of Gastroenterology, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Gastroenterology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Pharmacy, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, People’s Republic of ChinaCorrespondence: Shi-Gang Ding, Department of Gastroenterology, Peking University Third Hospital, Beijing, People’s Republic of China, Email dingshigang222@163.com Yu Lan, Department of Gastroenterology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China, Email lany_2022@163.comBackground: Minocycline, a derivative of tetracycline, has anti-Helicobacter pylori (H. pylori) properties and can be used to treat H. pylori infection. However, only a few randomized controlled trials (RCTs) have investigated the efficacy of minocycline-containing quadruple therapy (MCQT) in treating H. pylori infection. This study aimed to determine the efficacy and safety of MCQT and investigate the factors influencing both aspects.Methods: This was a retrospective cohort study. Patients diagnosed with H. pylori infection between January 1, 2022, and July 31, 2023 at. The primary outcome was the eradication rate of H. pylori, and the secondary outcome was the number and type of adverse events.Results: A total of 828 patients were included in this study. The overall H. pylori eradication rate among the included patients at 95% confidence interval (CI) (Range 0.864 to 0.907) was 88.53%. The H. pylori eradication rate for patients who received MCQT regimen as the primary therapy was 92.28% (95% CI: 0.901– 0.945), significantly higher than that of patients who received MCQT as rescue therapy (80.81%; 95% CI: 0.761– 0.855, P= 0.003). Adverse events, including dizziness, abdominal distension, diarrhea, nausea, abdominal discomfort, constipation, headache, rash, sleep disorder, palpitation, backache, and anorexia, occurred in 185 (22.34%) patients, with dizziness being the most common (75/828, 9.06%). Compliance with MCQT therapy was an independent factor influencing H. pylori eradication in patients receiving MCQT as a primary therapy. Compliance and presence or absence of H. pylori infection symptoms at the time of screening were independent factors influencing H. Pylori eradication in patients receiving MCQT as rescue therapy. Factors that influenced the occurrence of adverse events included reasons for H. pylori infection screening, residence, treatment compliance, and the use of acid-suppressant regimens.Conclusion: MCQT regimens were effective in H. pylori infection eradication, and the treatment resulted only in fewer adverse events when used as primary or rescue therapies for H. pylori infection treatment. Future prospective studies with larger sample sizes and more comprehensive data are needed to validate our findings.Keywords: Helicobacter pylori, minocycline, cohort study

Ji-Rong Yang,1 Ying-Yuan Li,2 Tao-Jia Ran,1 Xiao-Yu Lin,1 Jin-Yan Xu,1 Shao-Li Zhou,1 Pin-Jie Huang1 1Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Anesthesiology, Huadu District People’s Hospital, Guangzhou, Guangdong Province, People’s Republic of ChinaCorrespondence: Pin-Jie Huang; Shao-Li Zhou, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, Guangdong Province, People’s Republic of China, Email hpjie@126.com; 13610272308@139.comPurpose: We aimed to evaluate the effect of intravenous esketamine combined with dexmedetomidine as supplemental analgesia in reducing intraoperative visceral pain during elective cesarean section under combined spinal-epidural anesthesia (CSEA).Patients and Methods: A total of 269 parturients scheduled for elective cesarean section under CSEA between May 2023 and August 2023 were assessed. The parturients were randomly allocated to receiving either intravenous infusion of 0.3-mg/kg esketamine combined with 0.5-μg/kg dexmedetomidine (group ED, n=76), 0.5-μg/kg dexmedetomidine (group D, n=76), or normal saline (group C, n=76) after umbilical cord clamping. The primary outcome was intraoperative visceral pain. Secondary outcomes included the visual analog scale (VAS) score for pain evaluation and other intraoperative complications.Results: The incidence of visceral pain was lower in group ED [9 (12.7%)] than in group D [32 (43.8%)] and group C [36 (48.6%), P < 0.0001]. The VAS score was also lower in group ED when exploring abdominal cavity [0 (0), P < 0.0001] and suturing the muscle layer [0 (0), P =0.036]. The mean arterial pressure was higher in group D [83 (9) mmHg] and group ED [81 (11) mmHg] than in group C [75 (10) mmHg, P < 0.0001] after solution infusion. The heart rate after infusion of the solution was lower in group D [80 (12) bpm] than in group C [86 (14) bpm] and group ED [85 (12) bpm, P = 0.016]. The incidence of transient neurologic or mental symptoms was higher in group ED compared to group C and group D (76.1% vs 18.9% vs 23.3%, P< 0.0001).Conclusion: During cesarean section, 0.3-mg/kg esketamine combined with 0.5-μg/kg dexmedetomidine can alleviate visceral traction pain and provide stable hemodynamics. Parturients receiving this regimen may experience transient neurologic or mental symptoms that can spontaneously resolve at the end of the surgery.Plain language summary: Some parturients endure experience indescribable pain and discomfort during fetal delivery. Esketamine combined with dexmedetomidine can alleviate this pain during cesarean section under combined spinal-epidural anesthesia. However, after intravenous injection of esketamine and dexmedetomidine, the parturients may experience nightmares, dizziness, hallucinations, and drowsiness, etc.Keywords: cesarean section, dexmedetomidine, esketamine, CSEA, visceral pain

Chih-Yen Hsiao,1 Yi-Chien Lee,2,3 Douglas JH Shyu,4 Che-Ping Su,5 Man-Yi Lin,5 Nai-Yu Guo,6 Cheng-Lun Chiang,1 Yih-Yuan Chen5 1Division of Nephrology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan; 2Department of Internal Medicine, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City, Taiwan; 3School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; 4Department of Biological Science and Technology, National Pingtung University of Science and Technology, Neipu, Pingtung, Taiwan; 5Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan; 6Department of Respiratory Care, Chang-Gung University of Science and Technology, Chiayi, TaiwanCorrespondence: Yih-Yuan Chen, Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan, Tel +886-5-271-7795, Email yychen@mail.ncyu.edu.twObjective: The most common extraintestinal pathogen and infection site is uropathogenic Escherichia coli (UPEC), which causes urinary tract infections (UTIs). UPEC is also a common pathogen in bloodstream infections; in severe cases, it can lead to death. Although host and bacterial virulence factors have been demonstrated to be associated with UTI pathogenesis, the role of the related contributing factors in UTI and urinary source bacteremia is not yet fully understood. This study aimed to compare and analyze the factors contributing to urinary bacteremia in patients with UTI.Methods: A total of 171 E. coli strains collected from patients with UTI and urinary source bacteremia at Chiayi Christian Hospital were used. Phylogenetic groups and virulence factors were determined using PCR. Drug resistance patterns were determined using the disk diffusion assay.Results: Previous studies have demonstrated that fimbriae and papGII may be associated with first-step infections and severe UTIs, respectively. As expected, highly virulent E. coli strains (belonging to the phylogenetic B2 and D groups) were dominant in the bacteremic UTI (90%) and UTI (86.27%) groups. However, our results showed that the UTI group had a significantly higher prevalence of sfa/focDE (belonging to the S and FIC fimbriae) than the bacteremic UTI group (29.4% vs 12.5%; p=0.008). In the bacteremic group, we found that sfa/focDE was only detected in highly virulent strains. The bacteremic UTI group had a significantly higher prevalence of papGII (belonging to P fimbriae) than the UTI group (55.8% vs 37.3%; p=0.026). In addition, the P fimbriae gene cluster, including papC, papEF, and papGII, was predominant in highly virulent strains. Notably, our results show that multidrug-resistant (MDR) strains were significantly less virulent than non MDR strains.Conclusion: Taken together, our results provide insights into the contributing factors in patients with UTI and urinary bacteremia.Keywords: Escherichia coli, urinary tract infection, urinary source bacteremia, virulence factors, multidrug resistance

Yuan Ze,1 Hui-Ming Tu,2 Yuan-Yuan Zhao,1 Lin Zhang3,4 1Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China; 2Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, 214122, People’s Republic of China; 3Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, 230026, People’s Republic of China; 4School of Population Medicine and Public Health, Peking Union Medical College/Chinese Academy of Medical Sciences, Beijing, 100053, People’s Republic of ChinaCorrespondence: Hui-Ming Tu, Department of Gastroenterology, Affiliated Hospital of Jiangnan University, No. 1000, Hefeng Road, Binhu District, Wuxi, 214122, People’s Republic of China, Tel +86-13861753621, Email tuhuiming1891@163.com Yuan-Yuan Zhao, Tumor Research and Therapy Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Weiqi Road, Huaiyin District, Jinan, 250021, People’s Republic of China, Tel +86-13589097201, Email zhaoyuanyuan21@outlook.comPurpose: This study aimed to develop and validate a nomogram for predicting positive colonoscopy results using the data from non-invasive screening strategies.Methods: The volunteers participated in primary colorectal cancer (CRC) screenings using Asia-Pacific colorectal screening (APCS) scoring, faecal immunochemical testing (FIT) and stool deoxyribonucleic acid (sDNA) testing and underwent a colonoscopy. The positive colonoscopy results included CRC, advanced adenoma (AA), high-grade intraepithelial neoplasia (HGIN), and low-grade intraepithelial neoplasia (LGIN). The enrolled participants were randomly selected for training and validation sets in a 7:3 ratio. A model for predicting positive colonoscopy results was virtualized by the nomogram using logistic regression analysis.Results: Among the 179 enrolled participants, 125 were assigned to training set, while 54 were assigned to validation set. After multivariable logistic regression was done, APCS score, FIT result, and sDNA result were all identified as the predictors for positive colonoscopy results. A model that incorporated the above independent predictors was developed and presented as a nomogram. The C-index of the nomogram in the validation set was 0.768 (95% CI, 0.644– 0.891). The calibration curve demonstrated a good agreement between prediction and observation. The decision curve analysis (DCA) curve showed that the model achieved a net benefit across all threshold probabilities. The AUC of the prediction model for predicting positive colonoscopy results was much higher than that of the FIT + sDNA test scheme.Conclusion: The nomogram for predicting positive colonoscopy results was successfully developed based on 3 non-invasive screening tools (APCS scoring, FIT and sDNA test).Keywords: nomogram, colorectal cancer, primary screening, faecal immunochemical testing, stool deoxyribonucleic acid

Bang-Bin Chen,1,2 Po-Chin Liang,1– 3 Tiffany Ting-Fang Shih,1,2 Tsung-Hao Liu,4– 6 Ying-Chun Shen,4– 6 Li-Chun Lu,4– 6 Zhong-Zhe Lin,4,6 Chiun Hsu,4– 6 Chih-Hung Hsu,4– 6 Ann-Lii Cheng,4– 7 Yu-Yun Shao4– 6 1Department of Medical Imaging, National Taiwan University Hospital, Taipei City, Taiwan; 2Department of Radiology, College of Medicine, National Taiwan University, Taipei City, Taiwan; 3Department of Medical Imaging, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu City, 300, Taiwan; 4Department of Oncology, National Taiwan University Hospital, Taipei City, Taiwan; 5Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei City, Taiwan; 6Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan; 7Department of Internal Medicine, National Taiwan University Hospital, Taipei, TaiwanCorrespondence: Yu-Yun Shao, Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei City, 100, Taiwan, Tel +886-2 23123456 ext. 66008, Fax +886-2 23711174, Email yuyunshao@gmail.comPurpose: We investigated whether spleen volume (SV) changes were associated with treatment outcomes in advanced hepatocellular carcinoma (HCC) patients who received immunotherapy or first-line sorafenib.Patients and Methods: Patients with advanced HCC who underwent immunotherapy or first-line sorafenib at our institute were retrospectively analyzed. CT was used to measure SV before and within 3 months of treatment initiation. Tumor assessment followed Response Evaluation Criteria in Solid Tumors version 1.1. The association between SV change and tumor response or progression-free survival (PFS) was analyzed. The inverse probability of treatment weighting (IPTW) was used to adjust for differences in baseline characteristics.Results: The immunotherapy group comprised 143 patients (124 men, mean age, 59.8 years ± 11.2 [standard deviation]), while the sorafenib group had 57 (47 men, mean age, 59.6 years ± 9.9). SV increased in 108 (75.5%) immunotherapy and 21 (36.8%) sorafenib patients. In the immunotherapy group, patients with increased SV were more likely than those with decreased SV to have a higher disease control rate (76.9% vs 57.1%, p = 0.024) and durable clinical benefit (52.8% vs 25.7%, p = 0.005). It was also associated with extended PFS in the immunotherapy group in both the univariate (p = 0.028) and multivariate (p = 0.014) analysis. By contrast, in the sorafenib group, an increased in SV was not associated with treatment response but was presumably associated with reduced PFS (p = 0.072) in the multivariate analysis. After IPTW adjustment, the increase in SV remained a significant predictor for DCB and PFS in the immunotherapy group.Conclusion: Most patients exhibited an increase in SV after the initiation of immunotherapy, which may be used to predict response and prognosis. However, this association was not observed in patients who received sorafenib.Plain Language Summary: The study provides significant evidence that an increase in spleen volume is associated with better treatment outcomes in advanced hepatocellular carcinoma patients undergoing immunotherapy. These findings offer oncologists a new potential biomarker for optimizing treatment strategies. Specifically, increased spleen volume could be used to predict higher rates of disease control and durable clinical benefits, allowing for more personalized care. Keywords: hepatocellular carcinoma, immunotherapy, sorafenib, response, survival

Ling Tang,1 Yu-Jia Wang,2 Yuan-Yuan Wang,2 Shu-Tong Li,3 Liang Kong,3 Xue-Tao Li,3 Ling-Ling Ma,1 Xiu-Xiu Liu1 1Department of Obstetrics and Gynecology, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China; 2Department of Pharmacy, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China; 3School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, People’s Republic of ChinaCorrespondence: Ling-Ling Ma; Xiu-Xiu Liu, Department of Obstetrics and Gynecology, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China, Email 826269013@qq.com; 1225949002@qq.comPurpose: Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG2000-HA and DSPE-PEG2000-TK-PEG5000, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration.Methods and Results: PEG-TK-HA-PDLPs were prepared by film dispersion, with ideal physicochemical properties and exhibits active targeting for enhanced cellular uptake. The ZIP synergy score for PTX and Dios was calculated using the online SynergyFinder software to be 3.15, indicating synergy. In vitro results showed that PEG-TK-HA-PDLPs were highly cytotoxic to ID8 cells, induced ID8 cell apoptosis, and inhibited ID8 cell migration and invasion. In vivo studies showed that PEG-TK-HA-PDLPs could prolong the circulation time in the blood, accumulate significantly in the tumor site, and effectively fight against angiogenesis with significant anti-tumor effects.Conclusion: The production of PEG-TK-HA-PDLPs is an effective strategy for the treatment of OC.Keywords: ovarian cancer, functional liposomes, paclitaxel, diosgenin, ROS-response, HA

Xiao-xiao Ni,1,&ast; Zhe-ying Liu,2,&ast; Yan-yan Zeng,1,&ast; Zhi-feng Liu2 1Department of Hyperbaric Oxygen Medicine and Rehabilitation, General Hospital of Southern Theater Command of PLA, Guangzhou, Guangdong, People’s Republic of China; 2Department of Medicine Intensive Care Unit, General Hospital of Southern Theater Command of PLA, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-feng Liu, Department of Medicine Intensive Care Unit, General Hospital of Southern Theatre Command of PLA, Guangzhou, Guangdong, People’s Republic of China, Email Zhifengliu7797@163.comBackground: Hyperthermia and multiple organ dysfunction syndrome (MODS) are the main characteristics of heatstroke and COVID-19. Differentiating between these illnesses is crucial during a summer COVID-19 pandemic, but cases of heatstroke comorbid with COVID-19 are rarely reported.Case description: We report the first case of heatstroke comorbid with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in a 52-year-old male. After receiving intravenous antibiotics, organ protection measures, and treatment for coagulation disorders, his fever and coma resolved. However, he developed dyspnea and cerebral hemorrhage after several days. This patient experienced a multi-pathogen pulmonary infection and an intractable coagulopathy that ultimately resulted in MODS and death.Conclusion: The combination of heatstroke and SARS-CoV-2 infection exacerbated inflammation, immune abnormalities, and coagulation disorders. The interaction between inflammation and coagulation disturbances contributed to the underlying mechanism in this case, highlighting the importance of early anti-infection, treatment for coagulopathy, immune regulation, and organ protection as crucial interventions.Keywords: heatstroke, COVID‐19, infection, coagulation disorder, cerebral hemorrhage

Tantry Maulina,1,2 Yohanes Yoppy Purnomo,3 Nadya Khamila,4 Devy Garna,5 Endang Sjamsudin,1 Arief Cahyanto6 1Oral and Maxillofacial Surgery Department, Faculty of Dentistry, Universitas Padjadjaran, Bandung, Indonesia; 2Dentistry Department, Radboud University, Nijmegen, the Netherlands; 3Faculty of Dentistry, Maranatha Christian University, Bandung, Indonesia; 4Oral Surgery and Maxillofacial Specialist Program, Faculty of Dentistry, Universitas Padjadjaran, Bandung, Indonesia; 5Periodontology Department, Faculty of Dentistry, Universitas Padjadjaran, Bandung, Indonesia; 6Department of Restorative Dentistry, Faculty of Dentistry, Universiti Malaya, Kuala Lumpur, MalaysiaCorrespondence: Tantry Maulina, Dentistry Department, Radboud University, Nijmegen, Gelderland, the Netherlands, Email tantry.maulina@unpad.ac.id; tantry.maulina@radboudumc.nlPurpose: Despite its well-acknowledged analgesic potential, curcumin’s low bioavailability has been recognized. Piperine, a substance naturally contained in pepper, has been known for its effect on increasing curcumin bioavailability. To investigate the analgesic potential of curcumin and piperine addition to curcumin patch used as adjuvant therapy in the management of acute postoperative orofacial pain.Patients and Methods: This pragmatic trial recruited 75 patients that underwent oromaxillofacial surgery at Unpad Dental Hospital, Bandung, Indonesia. Research participants were randomly assigned to three different groups: the first group that did not receive any intervention other than the post-operative standard treatment (POST), the second group that received POST and non-piperine curcumin patch, and the third group that received POST and piperine-combined curcumin patch. Participants’ pain intensity was evaluated by using the face, leg, activity, cry, and consolability (FLACC) pain scale and salivary prostaglandin-E2 (PGE2) level for two-time points, which were eight hours apart. All data were gathered and analyzed to compare the within and between-group differences.Results: Within groups comparison of the FLACC scores for two evaluation points showed significant differences for all groups (p < 0.01). For salivary PGE2 analysis, a comparison of the non-piperine group to the piperine group also showed significant results. Yet, when all three groups were compared, regardless of the differences, the results were not statistically significant.Conclusion: Despite of the proven efficacy of curcumin patch, the addition of piperine to the curcumin patch in the current study did not provide any significant effects. Further investigation is of importance.Keywords: curcumin, piperine, acute postoperative pain, oromaxillofacial surgery, cleft lip, cleft palate

Zhengjun Ma,1 Yanmei Zhang,1 Yupu Zhu,2 Minxuan Cui,2 Yutao Liu,2 Yun-You Duan,1 Li Fan,2 Li Zhang1 1Department of Ultrasound Medicine, Tangdu Hospital, Air Force Medical University, Xi’an, People’s Republic of China; 2Department of Pharmaceutical Chemistry and Analysis, School of Pharmacy, Air Force Medical University, Xi’an, People’s Republic of ChinaCorrespondence: Li Fan; Li Zhang, Email xxfanny@fmmu.edu.cn; lilyzhang319_20@hotmail.comIntroduction: Recently, nanobubbles (NBs) have gained significant traction in the field of tumor diagnosis and treatment owing to their distinctive advantages. However, the application of NBs is limited due to their restricted size and singular reflection section, resulting in low ultrasonic reflection.Methods: We synthesized a nano-scale ultrasound contrast agent (IR783-SiO2NPs@NB) by encapsulating SiO2 nanoparticles in an IR783-labeled lipid shell using an improved film hydration method. We characterized its physicochemical properties, examined its microscopic morphology, evaluated its stability and cytotoxicity, and assessed its contrast-enhanced ultrasound imaging capability both in vitro and in vivo.Results: The results show that IR783-SiO2NPs@NB had a “donut-type” composite microstructure, exhibited uniform particle size distribution (637.2 ± 86.4 nm), demonstrated excellent stability (30 min), high biocompatibility, remarkable tumor specific binding efficiency (99.78%), and an exceptional contrast-enhanced ultrasound imaging capability.Conclusion: Our newly developed multiple scattering NBs with tumor targeting capacity have excellent contrast-enhanced imaging capability, and they show relatively long contrast enhancement duration in solid tumors, thus providing a new approach to the structural design of NBs.Keywords: ultrasound contrast agents, nanobubbles, CEUS, scattering cross-section, SiO2 NPs

Qing-Ren Liu,1 Yu-Chen Dai,2 Mu-Huo Ji,3 Pan-Miao Liu,4 Yong-Yan Dong,4 Jian-Jun Yang4 1Department of Anesthesiology, Xishan People’s Hospital of Wuxi City, Wuxi, 214105, People’s Republic of China; 2Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, People’s Republic of China; 3Department of Anesthesiology, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, People’s Republic of China; 4Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, People’s Republic of ChinaCorrespondence: Jian-Jun Yang, Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, NO. 1 East Jianshe Road, Zhengzhou, 450052, People’s Republic of China, Email yjyangjj@126.comAbstract: Acute postsurgical pain (APSP) has received growing attention as a surgical outcome. When poorly controlled, APSP can affect short- and long-term outcomes in patients. Despite the steady increase in awareness about postoperative pain and standardization of pain prevention and treatment strategies, moderate-to-severe APSP is frequently reported in clinical practice. This is possibly because pain varies widely among individuals and is influenced by distinct factors, such as demographic, perioperative, psychological, and genetic factors. This review investigates the risk factors for APSP, including gender, age, obesity, smoking history, preoperative pain history, pain sensitivity, preoperative anxiety, depression, pain catastrophizing, expected postoperative pain, surgical fear, and genetic polymorphisms. By identifying patients having an increased risk of moderate-to-severe APSP at an early stage, clinicians can more effectively manage individualized analgesic treatment protocols with a combination of pharmacological and non-pharmacological interventions. This would alleviate the transition from APSP to chronic pain and reduce the severity of APSP-induced chronic physical disability and social psychological distress.Keywords: acute postoperative pain, acute postsurgical pain, risk factors, predictors

Ying Wang,1 Han-Xin Yao,1 Zhen-Yi Liu,1 Yi-Ting Wang,1 Si-Wen Zhang,2 Yuan-Yuan Song,1 Qin Zhang,1 Hai-Di Gao,1 Jian-Cheng Xu1 1Department of Laboratory Medicine, First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 2Department of Endocrinology & Metabolism, First Hospital of Jilin University, Changchun, 130021, People’s Republic of ChinaCorrespondence: Jian-Cheng Xu, Department of Laboratory Medicine, First Hospital of Jilin University, Changchun, 130021, People’s Republic of China, Tel/Fax +86-043188782595, Email xjc@jlu.edu.cnObjective: This study aimed to explore specific biochemical indicators and construct a risk prediction model for diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D).Methods: This study included 234 T2D patients, of whom 166 had DKD, at the First Hospital of Jilin University from January 2021 to July 2022. Clinical characteristics, such as age, gender, and typical hematological parameters, were collected and used for modeling. Five machine learning algorithms [Extreme Gradient Boosting (XGBoost), Gradient Boosting Machine (GBM), Support Vector Machine (SVM), Logistic Regression (LR), and Random Forest (RF)] were used to identify critical clinical and pathological features and to build a risk prediction model for DKD. Additionally, clinical data from 70 patients (nT2D = 20, nDKD = 50) were collected for external validation from the Third Hospital of Jilin University.Results: The RF algorithm demonstrated the best performance in predicting progression to DKD, identifying five major indicators: estimated glomerular filtration rate (eGFR), glycated albumin (GA), Uric acid, HbA1c, and Zinc (Zn). The prediction model showed sufficient predictive accuracy with area under the curve (AUC) values of 0.960 (95% CI: 0.936– 0.984) and 0.9326 (95% CI: 0.8747– 0.9885) in the internal validation set and external validation set, respectively. The diagnostic efficacy of the RF model (AUC = 0.960) was significantly higher than each of the five features screened with the highest feature importance in the RF model.Conclusion: The online DKD risk prediction model constructed using the RF algorithm was selected based on its strong performance in the internal validation.Keywords: diabetic kidney disease, type 2 diabetes, machine learning model, random forest algorithm

Xiaomei Cui,1,2 Ting Zhang,2 Tao Xie,2 Fang-xi Guo,2 Yu-ying Zhang,2 Yuan-jia Deng,2 Qi Wang,1,2 Yi-xing Guo,1,2 Ming-hua Dong,1,2 Xiao-ting Luo1,3 1Key Laboratory of Cardio Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China; 2School of Public Health and Health Management, Gannan Medical University, Ganzhou, People’s Republic of China; 3School of General Medicine, Gannan Medical University, Ganzhou, People’s Republic of ChinaCorrespondence: Xiao-ting Luo, Golden Campus of Gannan Medical University, Zhanggong District, Ganzhou City, Jiangxi Province, People’s Republic of China, Tel +86 13677975578, Email xtluo76@163.comAbstract: Among cardiovascular diseases, hypertension is the most important risk factor for morbidity and mortality worldwide, and its pathogenesis is complex, involving genetic, dietary and environmental factors. The characteristics of the gut microbiota can vary in response to increased blood pressure (BP) and influence the development and progression of hypertension. This paper describes five aspects of the relationship between hypertension and the gut microbiota, namely, the different types of gut microbiota, metabolites of the gut microbiota, sympathetic activation, gut–brain interactions, the effects of exercise and dietary patterns and the treatment of the gut microbiota through probiotics, faecal microbiota transplantation (FMT) and herbal remedies, providing new clues for the future prevention of hypertension. Diet, exercise and traditional Chinese medicine may contribute to long-term improvements in hypertension, although the effects of probiotics and FMT still need to be validated in large populations. Keywords: blood pressure, metabolites, gut-brain, treatment

Abstract Background Umbilical cord blood (UCB) cells are a promising treatment for preterm brain injury. Access to allogeneic sources of UCB cells offer the potential for early administration to optimise their therapeutic capacities. As preterm infants often require ventilatory support, which can contribute to preterm brain injury, we investigated the efficacy of early UCB cell administration following ventilation to reduce white matter inflammation and injury. Methods Preterm fetal sheep (0.85 gestation) were randomly allocated to no ventilation (SHAM; n = 5) or 15 min ex utero high tidal volume ventilation. One hour following ventilation, fetuses were randomly allocated to i.v. administration of saline (VENT; n = 7) or allogeneic term-derived UCB cells (24.5 ± 5.0 million cells/kg; VENT + UCB; n = 7). Twenty-four hours after ventilation, lambs were delivered for magnetic resonance imaging and post-mortem brain tissue collected. Arterial plasma was collected throughout the experiment for cytokine analyses. To further investigate the results from the in vivo study, mononuclear cells (MNCs) isolated from human UCB were subjected to in vitro cytokine-spiked culture medium (TNFα and/or IFNγ; 10 ng/mL; n = 3/group) for 16 h then supernatant and cells collected for protein and mRNA assessments respectively. Results In VENT + UCB lambs, systemic IFNγ levels increased and by 24 h, there was white matter neuroglial activation, vascular damage, reduced oligodendrocytes, and increased average, radial and mean diffusivity compared to VENT and SHAM. No evidence of white matter inflammation or injury was present in VENT lambs, except for mRNA downregulation of OCLN and CLDN1 compared to SHAM. In vitro, MNCs subjected to TNFα and/or IFNγ displayed both pro- and anti-inflammatory characteristics indicated by changes in cytokine (IL-18 & IL-10) and growth factor (BDNF & VEGF) gene and protein expression compared to controls. Conclusions UCB cells administered early after brief high tidal volume ventilation in preterm fetal sheep causes white matter injury, and the mechanisms underlying these changes are likely dysregulated responses of the UCB cells to the degree of injury/inflammation already present. If immunomodulatory therapies such as UCB cells are to become a therapeutic strategy for preterm brain injury, especially after ventilation, our study suggests that the inflammatory state of the preterm infant should be considered when timing UCB cells administration.

Ming-Ming Ma,1,&ast; Yao-Yao Xu,2,&ast; Li-Hua Sun,1,&ast; Wen-Jie Cui,1 Miao Fan,3 Su Zhang,4 Lei Liu,5 Ling-Zhi Wu,6 Liu-Cheng Li7 1Department of Diagnostic Ultrasound & Echocardiography, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, People’s Republic of China; 2Department of Pharmacy, The People’s Hospital of Pingyang, Wenzhou, 325400, People’s Republic of China; 3Department of Pharmacy, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, People’s Republic of China; 4Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 5Department of Orthopaedics, Shaoxing Hospital of Traditional Chinese Medicine, Shaoxing, 312000, People’s Republic of China; 6Department of Pharmacy, The Affiliated Hospital of Jiaxing University (The First Hospital of Jiaxing), Jiaxing, 314000, People’s Republic of China; 7Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liu-Cheng Li, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Hangzhou, 310016, People’s Republic of China, Email 3415116@zju.edu.cn Ling-Zhi Wu, The Affiliated Hospital of Jiaxing University (The First Hospital of Jiaxing), No. 1882 South Central Road, Jiaxing, 314000, People’s Republic of China, Email wulingzhi1992@163.comAbstract: Surveillance of drug safety is an important aspect in the routine medical care. Adverse events caused by real-world drug utilization has become one of the leading causes of death and an urgent issue in the field of toxicology. Cardiovascular disease is now the leading cause of fatal diseases in most countries, especially in the elderly population who often suffer from multiple diseases and need long-term multidrug therapy. Among which, statins have been widely used to lower bad cholesterol and regress coronary plaque mainly in patients with hyperlipidemia and atherosclerotic cardiovascular diseases (ASCVD). Although the real-world benefits of statins are significant, different degrees and types of adverse drug reactions (ADR) such as liver dysfunction and muscle injury, have a great impact on the original treatment regimens as well as the quality of life. This review describes the epidemiology, mechanisms, early identification and post-intervention of statin-associated liver dysfunction and muscle injury based on the updated clinical evidence. It provides systematic and comprehensive guidance and necessary supplement for the clinical safety of statin use in cardiovascular diseases.Keywords: statin, cardiovascular diseases, liver dysfunction, muscle injury, countermeasures

Yong-Yu Yang,1,2 Rong-Rong Deng,3 Da-Xiong Xiang1,2 1Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2Hunan Provincial Engineering Research Central of Translational Medical and Innovative Drug, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 3School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Yong-Yu Yang; Da-Xiong Xiang, Department of Pharmacy, The Second Xiangya Hospital, Central South University, 139&num;, Renmin Middle Road, Changsha, Hunan, 410011, People’s Republic of China, Tel/Fax +86-731-85292129, Email yongyuyang@csu.edu.cn; xiangdaxiong@csu.edu.cnBackground: Ferroptosis plays a crucial role in the occurrence and development of cerebral ischemia-reperfusion (I/R) injury and is regulated by mitogen-activated protein kinase 1/2 (ERK1/2). In China, Naodesheng Pills (NDSP) are prescribed to prevent and treat cerebrosclerosis and stroke. However, the protective effects and mechanism of action of NDSP against cerebral I/R-induced ferroptosis remain unclear. We investigated whether NDSP exerts its protective effects against I/R injury by regulating ferroptosis and aimed to elucidate the underlying mechanisms.Methods: The efficacy of NDSP was evaluated using a Sprague-Dawley rat model of middle cerebral artery occlusion and an in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) model. Brain injury was assessed using 2,3,5-triphenyltetrazolium chloride (TTC), hematoxylin and eosin staining, Nissl staining, and neurological scoring. Western blotting was performed to determine the expression levels of glutathione peroxidase 4 (GPX4), divalent metal-ion transporter-1 (DMT1), solute carrier family 7 member 11 (SLC7A11), and transferrin receptor 1 (TFR1). Iron levels, oxidative stress, and mitochondrial morphology were also evaluated. Network pharmacology was used to assess the associated mechanisms.Results: NDSP (1.08 g/kg) significantly improved cerebral infarct area, cerebral water content, neurological scores, and cerebral tissue damage. Furthermore, NDSP inhibited I/R- and OGD/R-induced ferroptosis, as evidenced by the increased protein expression of GPX4 and SLC7A11, suppression of TFR1 and DMT1, and an overall reduction in oxidative stress and Fe2+ levels. The protective effects of NDSP in vitro were abolished by the GPX4 inhibitor RSL3. Network pharmacology analysis revealed that ERK1/2 was the core target gene and that NDSP reduced the amount of phosphorylated ERK1/2.Conclusion: NDSP exerts its protective effects against I/R by inhibiting cerebral I/R-induced ferroptosis, and this mechanism is associated with the regulation of ferroptosis via the ERK1/2 signaling pathway.Keywords: Naodesheng pills, ferroptosis, cerebral ischemia/reperfusion, glutathione peroxidase 4, mitogen-activated protein kinase 1/2

Yun-Yu Kuo,1 Jason Chen-Chieh Fang,2 I-Kuan Wang,3 Chiung-Shing Huang,4 Hui-Ling Chen,1,&ast; Tzung-Hai Yen5,&ast; 1Department of Dentistry and Craniofacial Orthodontics, Chang Gung Memorial Hospital, Taoyuan, Linkou, 333, Taiwan; 2Chang Gung Memorial Hospital, Keelung, 204, Taiwan; 3Department of Nephrology, China Medical University Hospital, and College of Medicine, China Medical University, Taichung, 406, Taiwan; 4Department of Craniofacial Orthodontics, Craniofacial Research Center, Chang Gung Memorial Hospital, Taipei, 105, Taiwan; 5Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, and College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan&ast;These authors contributed equally to this workCorrespondence: Hui-Ling Chen; Tzung-Hai Yen, 5 Fu-Hsing Street, Taoyuan, Kweishan, 333, Taiwan, Tel +886 3 3281200 ext 7840, Fax +886 3 3282173, Email ma3608@cgmh.org.tw; m19570@cgmh.org.twPurpose: There is an overall paucity of data examining the specific details of orthodontic patients’ patterns or orthodontic service disruptions possibly influenced by COVID-19 pandemic. Therefore, this study aimed to explore the impact of the COVID-19 pandemic on orthodontic clinic disruption regarding the change in adult patients’ characteristics and decisions of orthodontic treatment devices.Patients and Methods: A retrospective sample of 311 patients receiving orthodontic treatment from 2018 to 2022 were collected and divided into two groups: before (n = 167) and during (n = 144) the COVID-19 pandemic. Demographics, dental indices, the index of complexity outcome and need (ICON), and the degree of treatment difficulty were analyzed.Results: There were fewer students among patients during the COVID-19 pandemic than before (24.5% versus 35.9%, P = 0.036). Compared with patients before the pandemic, more patients selected ceramic brackets or Invisalign during the pandemic (P = 0.022). There were higher percentage of class I dental malocclusions among patients during than before the COVID-19 pandemic (P = 0.044). Moreover, the ICON score and the score of the degree of treatment difficulty were both significantly lower for patients during than before the COVID-19 pandemic (63.9± 14.0 versus 58.3± 15.3, P=0.001 and 7.4± 2.6 versus 6.8± 2.6, P=0.049, respectively).Conclusion: The COVID-19 pandemic influenced the characteristics and decisions of orthodontic patients. Those who still came to the orthodontic clinic despite the COVID-19 outbreak may have been those with less malocclusion severity and treatment difficulty. Besides, during the time of covid-19 pandemic, more patients chose ceramic bracket and Invisalign as their orthodontic treatment device rather than conventional or self-ligating metal brackets.Keywords: COVID-19, pandemic, orthodontic, Invisalign, bracket, dental malocclusion, sagittal skeletal relationship, index of complexity outcome and need, degree of treatment difficulty

Jing-Fan Gao,&ast; Yue-Yan Dong,&ast; Xin Jin, Li-Jun Dai, Jing-Rao Wang, Hong Zhang Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Zhang, Department of Eye Hospital, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China, Email zhanghong@hrbmu.edu.cnObjective: Keratoconus is a commonly progressive and blinding corneal disorder. Iron metabolism and oxidative stress play crucial roles in both keratoconus and ferroptosis. However, the association between keratoconus and ferroptosis is currently unclear. This study aimed to analyze and verify the role of ferroptosis-related genes (FRGs) in the pathogenesis of keratoconus through bioinformatics.Methods: We first obtained keratoconus-related datasets and FRGs. Then, the differentially expressed FRGs (DE-FRGs) associated with keratoconus were screened through analysis, followed by analysis of their biological functions. Subsequently, the LASSO and SVM-RFE algorithms were used to screen for diagnostic biomarkers. GSEA was performed to explore the potential functions of the marker genes. Finally, the associations between these biomarkers and immune cells were analyzed. qRT‒PCR was used to detect the expression of these biomarkers in corneal tissues.Results: A total of 39 DE-FRGs were screened, and functional enrichment analysis revealed that the DE-FRGs were closely related to apoptosis, oxidative stress, and the immune response. Then, using multiple algorithms, 6 diagnostic biomarkers were selected, and the ROC curve was used to verify their risk prediction ability. In addition, based on CIBERSORT analysis, alterations in the immune microenvironment of keratoconus patients might be associated with H19, GCH1, CHAC1, and CDKN1A. Finally, qRT‒PCR confirmed that the expression of H19 and CHAC1 was elevated in the keratoconus group.Conclusion: This study identified 6 DE-FRGs, 4 of which were associated with immune infiltrating cells, and established a diagnostic model with predictive value for keratoconus.Keywords: keratoconus, ferroptosis, immune infiltration, machine learning

Ying Chen,1,2,&ast; Wen-Xia Li,1,2,&ast; Jia-Hua Wu,1,2 Geng-Hang Chen,2 Chun-Min Yang,1,2 Hai Lu,1,2 Xi Wang,3 Shu-Sen Wang,4 Heng Huang,5 Li Cai,6 Li Zhao,7 Rou-Jun Peng,8 Ying Lin,9 Jun Tang,3 Jian Zeng,10 Le-Hong Zhang,11 Yong-Li Ke,12 Xian-Ming Wang,13 Xin-Mei Liu,14 An-Qin Zhang,15 Fei Xu,4 Xi-Wen Bi,4 Jia-Jia Huang,4 Ji-Bin Li,16 Dan-Mei Pang,17 Cong Xue,4 Yan-Xia Shi,4 Zhen-Yu He,18 Huan-Xin Lin,18 Xin An,4 Wen Xia,4 Ye Cao,16 Ying Guo,16 Ruo-Xi Hong,4 Kui-Kui Jiang,4 Yong-Yi Zhong,4 Ge Zhang,19 Piyawan Tienchaiananda,20 Masahiro Oikawa,21 Zhong-Yu Yuan,4 Qian-Jun Chen22,23 1Department of Breast Surgery, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Breast Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Department of Breast Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 4Department of Medical Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 5Department of Breast Oncology, Lianjiang People’s Hospital, Lianjiang, People’s Republic of China; 6Department of Medical Oncology, The Affiliated Tumour Hospital of Harbin Medical University, Harbin, People’s Republic of China; 7Department of Breast Oncology, Guangzhou First People Hospital, Guangzhou, People’s Republic of China; 8Department of Integrated Therapy in Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 9Department of Breast Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 10Department of Breast Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 11Department of Breast Oncology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 12Department of Breast Oncology, General Hospital of PLA Guangzhou Military Area, Guangzhou, People’s Republic of China; 13Department of Breast Oncology, Shenzhen Second People’s Hospital, Shenzhen, People’s Republic of China; 14Department of Breast Oncology, Haikou People’s Hospital, Haikou, People’s Republic of China; 15Department of Breast Oncology, Maternal and Child Health Care Hospital of Guangdong Province, Guangzhou, People’s Republic of China; 16Department of Good Clinical Practice, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 17Department of Medical Oncology, Foshan First People’s Hospital, Foshan, People’s Republic of China; 18Department of Radiotherapy, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 19Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases (TMBJ), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong; 20Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Rangsit University, Rajavithi Hospital, Bangkok, Thailand; 21The Department of Breast Surgery, New-wa-kai Oikawa Hospital, Fukuoka, Japan; 22State Key Laboratory of Traditional Chinese Medicine Syndrome/Departments of Gynecologic Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 23State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian-Jun Chen, 55N, Neihuanxi Road, Guangzhou, Guangdong, 510006, People’s Republic of China, Tel +86 1868883505, Email cqj55@163.com Zhong-Yu Yuan, 651 Dongfeng Road, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86 13798027658, Email yuanzhy@sysucc.org.cnPurpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not.Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into “consistent” (standard acceptable dose) and “inconsistent” (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes.Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the “inconsistent” dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the “inconsistent” dose of anthracycline and taxane did not affect DFS compared with the “consistent” dose. Moreover, in the capecitabine group, the “inconsistent” anthracycline dose did not affect DFS compared with the “consistent” dose. However, patients with “consistent” taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06).Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.Keywords: adjuvant chemotherapy, capecitabine, SYSUCC-001, triple-negative breast cancer, TNBC

Hao Wu, Qing-Jie Ji, Yu-Yang Xu, Jian-Wei Zhu Department of Dermatology, Quzhou TCM Hospital at the Junction of Four Provinces Affiliated to Zhejiang Chinese Medical University, Quzhou, People’s Republic of ChinaCorrespondence: Jian-Wei Zhu, Email zjwmed@163.comAbstract: Pityriasis rosea (PR) is a common inflammatory, erythematous and scaly skin condition that usually affects individuals aged from 20 to 40 years old. The disease often exhibits a self-limiting course up to 6– 8 weeks. We report a 25-year-old female patient with a six-month history of red scaly rashes on the trunk and proximal limbs, accompanied by severe pruritus that has been remained ineffective conventional treatments. She was diagnosed as persistent pityriasis rosea. As abrocitinib has been proved to be effective for many inflammatory diseases, therefore in this case, we tried abrocitinib for the patient, and a good result had been achieved.Keywords: pityriasis rosea, abrocitinib, JAK-STAT pathway