Search

Xiangjun Chen,* Weiwei Li,* Qing Fan, Xiao Liu, Xuanxiang Zhai, Xiaoyi Shi, Wenting Li, Wei Hong School of Pharmacy, Shandong Engineering Research Center of New-Type Drug Loading & Releasing Technology and Preparation, Binzhou Medical University, Yantai, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Hong; Wenting Li, Email hongwei_sy@bzmc.edu.cn; liwenting1003@163.comIntroduction: Pseudomonas aeruginosa (P. aeruginosa)-induced pneumonia is marked by considerable infiltration of inflammatory cells and biofilm formation, which causes acute and transient lung inflammation and infection. Nevertheless, the discovery of alternative preventative and therapeutic methods is essential due to the high mortality rates in clinical settings and the resistance of P. aeruginosa infection to multiple medications.Purpose: In this research, we constructed amphiphilic Janus nanoparticles (JNPs, denoted as SSK1@PDA/CaP@CIP), loaded with hydrophobic SSK1, a β-galactosidase (β-gal)-activated prodrug for reducing macrophages, and hydrophilic ciprofloxacin (CIP), a classic antibiotic for treating infection. SSK1@PDA/CaP@CIP was designed to effectively attenuate inflammation, eradicate biofilms, and combat planktonic P. aeruginosa.Results: As expected, SSK1@PDA/CaP@CIP was able to target the infection site and demonstrated outstanding efficacy in treating P. aeruginosa strain PAO1-induced pneumonia by regulating macrophage infiltration to reduce inflammation and removing planktonic bacteria and biofilms to control infection. Additionally, the primary organs did not exhibit any discernible pathological changes following treatment with SSK1@PDA/CaP@CIP, which indicates superior biocompatibility throughout the treatment course.Discussion: In conclusion, our investigation introduced a promising approach to the treatment of pneumonia associated with PAO1.Keywords: Pseudomonas aeruginosa, pneumonia, inflammatory responses, β-galactosidase (β-gal)-activated prodrug, amphiphilic Janus nanoparticles

Jiahua Cheng,1,* Wujuan Li,1,* Lanlin Wang,1,* Yu Gao,1 Yueran Ma,1 Min Zhou,1 Tian Yang,1 Changwu Yue,1,2 Long Yan,3 Yuhong Lyu1,2 1Yan’an Key Laboratory of Microbial Drug Innovation and Transformation, School of Basic Medicine, Yan’an University, Yan’an, Shaanxi, People’s Republic of China; 2Shaanxi Engineering and Technological Research Center for Conversation and Utilization of Regional Biological Resources, Yan’an University, Yan’an, Shaanxi, People’s Republic of China; 3Medical Imaging Center, Yan’an Traditional Chinese Medicine Hospital, Yan’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Long Yan; Yuhong Lyu, Email yanlong840212@163.com; yuhonglyu@126.comPurpose: To explore the protective effects and mechanisms of Jiawei Qifuyin on APP/PS1 mice, a model for Alzheimer’s disease (AD).Methods: Network pharmacology tools were used to predict anti-AD targets and signaling pathways affected by Jiawei Qifuyin. In vitro studies assessed antioxidant and oxygen radical scavenging abilities, immune cell proliferation, and inflammatory cytokine levels in lipopolysaccharide-induced BV2 microglial cells. Cognitive ability in APP/PS1 mice was evaluated using the Morris Water Maze test. mRNA expression of neuroinflammatory factors, changes in intestinal microbiota, and short-chain fatty acid content were analyzed post-treatment.Results: Network pharmacology predicted that Jiawei Qifuyin affects AKT1, TNF-α, and AGE/RAGE pathways. It showed concentration-dependent antioxidant effects and modulated immune cell proliferation. IL-2, IL-6, and TNF-α levels in LPS-induced BV2 cells were significantly reduced. Treated animals exhibited improved cognitive performance, decreased brain amyloid-beta levels, and downregulated expression of IL-1β, IL-6, RAGE, and NF-κB. Significant changes in intestinal microbiota composition and SCFA content were observed.Conclusion: Jiawei Qifuyin may enhance immunity and improve cognitive impairment in APP/PS1 mice through regulation of inflammatory factors, gut microbiota, and the gut-brain axis.Keywords: Alzheimer’s disease, Jiawei Qifuyin, neuroinflammation, intestinal microbiota, short chain fatty acid

Weichao Li,1,2 YuYan Liu,2 Xunhu Gu1 1Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Anesthesiology, Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University, QingYuan, Guangdong, People’s Republic of ChinaCorrespondence: Xunhu Gu, Doctor of Medicine (MD), Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China, Email 540523118@qq.comBackground: Catecholamine vasopressors are commonly used for intra- or post-operative hypotension for cardiac surgery, which have a side effect of new-onset atrial fibrillation (AF) and myocardial ischemia. However, it is not entirely clear whether catecholamine vasopressors increase the risk of new-onset AF after noncardiac surgery.Aim: The aim of this study was to analyze the association between the use of catecholamine vasopressors and the risk of developing new-onset AF after noncardiac surgery.Methods: In this prospective trial, available data from eligible elderly individuals receiving noncardiac surgery at a single center from November 2022 to January 2024 were gathered. Propensity score matching (PSM) was used to balance patient baseline characteristics and to control for confounders. To determine the association between catecholamine vasopressors and the risk of new-onset AF, univariate and multivariate logistic regression analyses were performed.Results: A total of 6000 subjects were included in this study (mean [SD] age, 70.73 [6.37] years; 910 [50.9%] males). After PSM, the patients were stratified into catecholamine vasopressor (n = 357) and comparator groups (n = 1432). A total of 18/357 patients in the catecholamine vasopressor group developed AF, and 25/1432 patients in the comparator group developed AF (incidence rate, 5.0% vs 1.7%). Compared with the comparator group, the catecholamine vasopressor group had an increased risk of new-onset AF (aOR, 2.77; 95% CI, 1.28– 5.89). Some sensitivity analyses also revealed consistent findings of increased new-onset AF risk associated with catecholamine vasopressor treatment.Conclusion: The findings from this study suggest that catecholamine vasopressor treatment is associated with an increased risk of new-onset AF and may help physicians select a modest medication for patients while also assessing the risk of new-onset AF. Keywords: catecholamine vasopressors, new-onset atrial fibrillation, risk, prospective trial, noncardiac procedures

Jing Sun,1,2,* Wengang Li,3,* Weiping He,3,* Yanping Yang,4,* Lewei Duan,5 Tingshi Su,6 Aimin Zhang,3 Tao Zhang,3 Xiaofang Zhao,7 Xiaoyun Chang,3 Xuezhang Duan1– 3 1 307 Clinical College of PLA, ANHUI Medical University, Beijing, People’s Republic of China; 2The Fifth Clinical College, ANHUI Medical University, Hefei, Anhui, People’s Republic of China; 3Department of Radiation Oncology, Senior Department of Oncology, The Fifth Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 4Department of Oncology, Kaifeng People’s Hospital, Kaifeng, Henan, People’s Republic of China; 5Laboratory of Epigenetics at Institutes of Biomedical Sciences, and Intelligent Medicine Institute, Fudan University, Shanghai, People’s Republic of China; 6Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of China; 7Graduate School of PLA Medical College, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xuezhang Duan, 307 Clinical College of PLA, ANHUI Medical University, No. 8 East Street, Fengtai District, Beijing, People’s Republic of China, Email duanxuezhang2006@163.comPurpose: Radiofrequency ablation (RFA) is a micro-invasive treatment for early-stage HCC patients. Stereotactic body radiation therapy (SBRT) has also been proven an effective and safe treatment for HCC patients. This multi-center study is to compare the efficacy of computed tomography (CT)-guided RFA and CT-based SBRT in naïve HCC patients with tumor diameters ≤ 5 cm.Patients and Methods: This retrospective cohort study included 1001 treatment-naïve HCC patients from three hospitals or medical centers. The patients received RFA (n = 481) or SBRT (n = 520) treatment between December 2011 and May 2019. Furthermore, subgroup analyses of all patients were conducted based on Couinaud’s classification of liver segments.Results: After matching, the local control (LC) rates of the SBRT group were better than those of the RFA group (p=0.024*), which mainly referred to the patients whose tumors were located in the S7/S8 (p=0.006*). Among patients with tumors located in S1, nineteen patients (19/21) underwent SBRT. The 1-, 3- and 5-year LC rates were 100%, 87.8% and 87.8% in the SBRT group, and the 1-, 3- and 5-year OS rates were 100%, 69.8% and 69.8%, respectively. Moreover, the OS rates in S5/S6 group in RFA were higher than those in SBRT group.Conclusion: The LC rates were better in the SBRT group than in the RFA group for the patients with lesions localized in S7/S8, and SBRT could also be a therapeutic option for patients with lesions in S1. Moreover, patients with tumors located in S5/S6 were better candidates for RFA treatment than SBRT.Keywords: Stereotactic body radiation therapy, Computed tomography-guided radiofrequency, Naive hepatocellular carcinoma, Couinaud’s segmentation

Fangyuan Lai,1,* Xiuqiong Huang,2,* Jiao Peng,3 Nannan He,4 Zhongqiang Cao,1 Yuhui Wu,4 Wei Li,5 Zebin Chen,1 Xuejuan Li1 1Department of Pharmacy, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 2Department of Pharmacy, The First People’s Hospital of Zhaoqing, Zhaoqing, People’s Republic of China; 3Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 4Department of Pediatric Intensive Care Unit, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 5Department of Pharmacy, The Third People’s Hospital of Shenzhen, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xuejuan Li, Department of Pharmacy, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China, Email xuejuanli@126.comObjective: The first-line treatment for severe Pneumocystis carinii pneumonia (PCP) is trimethoprim-sulfamethoxazole (TMP/SMZ). Here, we report a case involving 6-month-old child with a PCP infection, highlighting the role of clinical pharmacists in providing individualized pharmaceutical care and guidance through the process of therapeutic drug monitoring (TDM).Methods: The clinical pharmacist monitored the concentration of TMP/SMZ in the serum, urine and sputum of a 6-month-old child with PCP infection. To improve the serum levels of TMP/SMZ, the dose of TMP/SMZ was increased, while infusions of other medications were reduced to decrease the rate of drug excretion. Additionally, the patient received other supportive medications to enhance clinical therapeutic efficacy.Results: Clinical pharmacists observed that, despite administration of a sufficient dose of TMP/SMZ, plasma concentration of TMP/SMZ remained below the therapeutic window, while urine concentrations were extremely high. This phenomenon was attributed to Augmented Renal Clearance (ARC), often seen in critically ill patients and associated with increased renal clearance. Throughout treatment, the concentrations of SMZ remained below the minimum effective concentration, while the concentrations of TMP fell within the effective target range. However, sufficient therapeutic effects were ultimately achieved and observed in the patient, likely due to improved drug distribution in lung tissue (sputum) and the patient’s recovering immune functions. Finally, thanks to individualized pharmaceutical care from clinical pharmacists and the combined efforts of clinicians, the patient was discharged after 58 days of hospitalization.Conclusion: Throughout treatment, the clinical pharmacist played a vital role in optimizing the treatment plan based on the serum, urine and sputum concentrations of TMP/SMZ and providing pharmaceutical care to ensure a safe, rational and effective medications in children. Individualized dose adjustments, particularly high-dose TMP/SMZ guided by TDM, can significantly enhance the management of PCP in pediatric patients and support clinical pharmacists in delivering individualized pharmaceutical care.Keywords: Pneumocystis carinii pneumonia, trimethoprim/sulfamethoxazole, therapeutic drug monitoring, plasma drug concentration

Yihui Yu,1 Wei Li,1,2 Qian Li,1,2 Wenyan Liu,1,2 Sanquan Zhang,1,2 Xibao Zhang,1,2 Jingyao Liang1,2 1Institute of Dermatology, Guangzhou Medical University, Guangzhou, 510095, People’s Republic of China; 2Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, 510095, People’s Republic of ChinaCorrespondence: Jingyao Liang; Xibao Zhang, Email ljy20221228@163.com; gzpfbfzs@163.comAbstract: Vitiligo is a chronic autoimmune disorder characterized by depigmented patches of the skin. The treatment of vitiligo remains challenging, partly owing to the lack of efficient drug delivery system. Microneedles (MNs), an ideal transdermal drug delivery system, have emerged as promising drug delivery platform for vitiligo. Recently, the emergence of novel MNs with increased biocompatibility, including hydrogel and hollow MNs, further enhance the translational value of MNs in the treatment of vitiligo. However, up-to-date review of these advancements remains lacking. This review aims to summarize the most recent studies of MN-based drug delivery systems for vitiligo, highlighting the translational potential of MNs as a therapeutic platform for the treatment of vitiligo in the near future. Keywords: vitiligo treatment, microneedle design, advanced applications

Xinkai Luo,1,* Ying Wang,2,* Yufei Mao,3,* Xiaowei Xu,1,4 Weifeng Gu,1 Wen Li,1 Chaoming Mao,1 Tingting Zheng,1 Liyang Dong1 1Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 2Department of Respiratory Diseases, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, Jiangsu, People’s Republic of China; 3Department of Ultrasound Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 4Department of Laboratory Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liyang Dong; Tingting Zheng, Email liyangdong@ujs.edu.cn; tingtingzheng@ujs.edu.cnBackground: Nebulization of hypoxic human umbilical cord mesenchymal stem cell-derived extracellular vesicles (Hypo-EVs) can suppress airway inflammation and remodeling in a chronic asthmatic mouse; however, the exact mechanism remains unclear. Recently, airway epithelial barrier defects have been regarded as crucial therapeutic targets in asthma. The aim of this study was to investigate whether and how Hypo-EVs protect against the disruption of the airway epithelial barrier under asthmatic conditions.Methods: The therapeutic effects of Hypo-EVs on airway epithelial barrier defects were evaluated in ovalbumin (OVA)-induced asthmatic mice and in IL-4 and IL-13-induced HBE135-E6E7 cell models by detecting cell monolayer leakage and junctional protein expression. The protein levels in Hypo-EVs were determined by Western blotting, and a gene knockdown approach was used to investigate the biofactors in Hypo-EVs.Results: Nebulization of Hypo-EVs directly alleviated airway epithelial barrier defects in asthmatic mice, as evidenced by colocalization with bronchial epithelial cells, decreased albumin concentration, and increased ZO-1 and E-cadherin expression. In vitro, Hypo-EV treatment dramatically rescued the increase in airway cell permeability, and upregulated the ZO-1 and E-cadherin protein expressions. Based on WB analysis, we found that caveolin-1 (CAV-1) was strongly enriched in Hypo-EVs. The knockdown of CAV-1 protein levels in Hypo-EVs significantly impaired Hypo-EV-mediated barrier protection in vitro and in vivo. Moreover, CAV-1 knockdown significantly abolished the beneficial effects of Hypo-EVs on airway inflammation and remodeling in asthmatic mice. In addition, we showed that IL-4/IL-13-induced airway epithelial barrier defects were mainly related to activation of STAT6 phosphorylation (p-STAT6), and overexpression of CAV-1 or Hypo-EV treatment inhibited the levels of p-STAT6 in IL-4/IL-13-induced HBE135-E6E7 cells.Conclusion: Nebulization of Hypo-EVs can attenuate airway epithelial barrier defects in asthma by delivering CAV-1 to inhibit p-STAT6 expression and may be used to treat other barrier defect diseases.Keywords: nebulization, Hypo-EVs, asthma, airway epithelial barrier, caveolin-1

Ruidong Ma,* Wei Li,* Qiufeng Peng,* Ao Ren, Ling Zhao, Jiawei Li, Shiqiao Luo Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shiqiao Luo, Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Youyi Road 1st, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-15002355050, Email 202065@hospital.cqmu.edu.cnPurpose: Prior research has suggested a correlation between gallstones and depressive symptoms, yet the specifics of this relationship remain unclear. This study aims to explore the association between gallstones and depressive symptoms among adults.Patients and Methods: Initially, we conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2017 – March 2020. After propensity score matching (PSM) for participants with gallstones and those without gallstones, multivariate logistic regression analysis was used to explore the potential association between gallstones and depressive symptoms. This was followed by Mendelian randomization (MR) analysis to further elucidate the causal relationship between them. Using the genome-wide association study database, we extracted instrumental variables and performed bidirectional univariate and multivariate MR analyses.Results: In the cross-sectional study of NHANES 2017 – March 2020, 835 pairs of participants with comparable characteristics, both with and without gallstones, were identified after PSM. The multivariate adjusted logistic regression analyses revealed a significant association between gallstones and depressive symptoms [fully adjusted model: OR=1.821 (95% CI, 1.181– 2.808), P=0.007]. Subsequent MR analyses further clarified the causal relationship, indicating that genetically determined gallstones significantly increase the risk of developing depressive symptoms [forward univariate MR analysis: OR=1.04 (95% CI, 1.01– 1.06), P=0.002; multivariate MR analysis: OR=1.03 (95% CI, 1.01– 1.05), P=0.009], with no evidence of reverse causation [inverse univariate MR analysis: OR=1.28 (95% CI, 0.90– 1.83), P=0.17].Conclusion: Gallstones are a risk factor for depressive symptoms among adults. Hence, we recommend timely depression screening for patients diagnosed with gallstones, facilitating early detection and effective treatment of depressive symptoms, thus alleviating its impact on both individuals and society.Keywords: depressive symptoms, gallstones, risk factor, causality, genetic analysis, cross-sectional study

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

Yijia Guo,1– 3,&ast; Ruyun Zhang,4,&ast; Xinling Gan,5 Erli Wang,6 Shuihua Lu,7 Hui Jiang,3 Hongfei Duan,8 Zhengzhou Yuan,9 Weimin Li,2,3,10 Yong Liu1 1Department of Neurology, Chengdu Medical College, The First Affiliated Hospital, Chengdu, People’s Republic of China; 2Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 3Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Emergency, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Department of Radiology, The First People’s Hospital of Longquanyi District, Chengdu, People’s Republic of China; 7National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, Shenzhen Third People’s Hospital, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 8Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 9Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 10National Tuberculosis Clinical Laboratory of China, Beijing Key Laboratory in Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China&ast;These authors contributed equally to this work as first authorsCorrespondence: Yong Liu, Chengdu Medical College, The First Affiliated Hospital, No. 278, Middle Section, Baoguang Avenue, Xindu District, Chengdu, 610500, People’s Republic of China, Email 410578100@qq.comBackground: The predictors associated with clinical outcomes in patients with tuberculous meningitis (TBM) remain unclear. We aimed to analyse the relationship between systemic inflammation and clinical outcomes, as well as to explore whether systemic inflammation level influences the effectiveness of dexamethasone on treatment.Methods: Between January 2011 and December 2021, TBM patients admitted to five hospitals were observed consecutively. Baseline and post-treatment systemic inflammation levels were calculated using the neutrophil-lymphocyte-ratio (NLR). Generalized linear mixed models were employed to identify predictors of clinical outcomes. Propensity score matching and subgroup analyses were conducted to evaluate the effect of dexamethasone on treatment outcomes across different NLR levels.Results: A total of 1203 TBM patients were included in the study. During the follow-up, 144 (13.6%) participants experienced early neurological deterioration within 7 days after admission, and 345 (28.67%) exhibited poor functional outcome at the 12-month follow-up. Multivariate analysis revealed that post-treatment NLR was significantly associated with early neurological deterioration (OR=1.25; 95% CI, 1.14– 1.33; P< 0.001), and poor outcome (OR=1.34; 95% CI, 1.26– 1.45; P< 0.001). After propensity score matching, dexamethasone treatment was not associated with early neurological deterioration (OR=0.83; 95% CI, 0.42– 1.66; P=0.610) or poor outcome (OR=1.22; 95% CI, 0.49– 2.11; P=0.490) in the highest quartile of post-treatment NLR. The effect of dexamethasone on treatment outcomes did not significantly vary with disease severity stratification.Conclusion: Elevated systemic inflammation is an independent risk factor for neurological outcome in TBM patients. Further studies are required to investigate systemic inflammation in more severely affected population to better predict the outcomes following anti-inflammatory therapies.Keywords: tuberculous meningitis, systemic inflammation, neurological outcome

Zhengzheng Fu,1,&ast; Jingwen Zou,1,&ast; Jing Zhong,1 Jipang Zhan,1 Lian Zhang,1 Xiaoru Xie,1 Lai Zhang,1,2 Wenqiang Li,3 Renliang He1 1Department of Dermatologic Surgery and Dermatologic Oncology, Dermatology Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510000, People’s Republic of China; 2Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, 510006, People’s Republic of China; 3Engineering Technology Research Center for Sports Assistive Devices of Guangdong, Guangzhou Sport University, Guangzhou, Guangdong Province, 510500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenqiang Li; Renliang He, Department of Dermatologic Surgery and Dermatologic Oncology, Dermatology Hospital of Southern Medical University, Guangdong Provincial Dermatology Hospital, 2 Lujing Road, Yuexiu District, Guangzhou, Guangdong Province, 510000, People’s Republic of China, Email liwq@gzsport.edu.cn; zshrl2006@smu.edu.cnBackground: The skin regulates body processes. When damaged, it is prone to breeding bacteria, causing inflammation and impeding wound healing. There is an urgent need for new dressings that can combat bacteria to aid in infectious wound repair.Methods: In this study, a curcumin-loaded nanocomposite hydrogel dressing (GelMA/AHA-Gel@Cur) with antibacterial properties and strong toughness was synthesized, designed to combine the modified gelatin-based hydrogel (GelMA/AHA) with curcumin-coated gelatin (Gel@Cur) nanoparticles to promote the healing of bacterial infection wounds. Under UV irradiation, methylacrylylated gelatin (GelMA) and aldehyaluronic acid (AHA) formed a composite network hydrogel through radical polymerization and Schiff base reaction. Meanwhile, the residual aldehyde group on the molecular chain of AHA securely locked Gel@Cur nanoparticles in the hydrogel network through Schiff base reaction.Results: The addition of Gel@Cur nanoparticles not only enhanced the hydrogel’s mechanical strength but also facilitated a sustained, gradual release of curcumin, endowing the composite hydrogel with robust antimicrobial capabilities. In an animal model of infected wounds, the composite hydrogel significantly improved wound closure, healing, and vascularization compared to the control group. Hemocompatibility tests confirmed the hydrogel’s safety, with a hemolysis ratio of just 0.45%. Histological evaluation following treatment with the composite hydrogel showed improved tissue architecture, increased collagen deposition, and regeneration of dermal gland structures.Conclusion: The GelMA/AHA-Gel@Cur composite hydrogel exhibits excellent mechanical properties, potent antimicrobial activity, and controlled drug release, along with superior cell and hemocompatibility. These characteristics make it a promising material for infected wound repair and a potential candidate for clinical skin regeneration applications. Keywords: Nanocomposite hydrogel dressings, infected wound repair, antibacterial properties, drug delivery

Luwei Xiang,1,&ast; Jing Wang,1,&ast; Wen Li,1,2 Hongfang Ye1,2 1School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 2Nursing Department, Nanjing Drum Tower Hospital, Nanjing, 210008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongfang Ye, School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Email 13915969627@163.comPurpose: To explore the status quo and influencing factors of personal mastery in Chinese patients with chronic heart failure, based on the analysis of patient characteristics.Methods: The sample of the study comprised 249 chronic heart failure patients who visited a university hospital in China. We collected the data using general demographic Information, personal mastery scale, the Simple Coping Style Questionnaire and Minnesota Living With Heart Failure Quality of Life Questionnaire (MLHFQ). SPSS26.0 was used to describe the survey results statistically, and univariate analysis, Pearson correlation analysis and multiple linear regression were used to analyze the influencing factors of personal sense of control.Results: Chronic heart failure patients’ total personal mastery scores were (20.63± 4.486), which is in the medium level. Multiple linear regression analysis shows that Age group (β=− 1.627, p=0.036), NYHA functional classification (β=− 1.563, P< 0.001), Positive coping style (β= 0.088, P=0.004) and MLHFQ (β= − 0.121 P< 0.001) significantly influenced patients’ personal mastery (P< 0.001).Conclusion: Our study suggests that the personal mastery of patients with chronic heart failure is at a moderate level in China. Additionally, age group, NYHA functional classification, Positive coping style and MLHFQ emerged as significant influencing factors. Clinical staff should dynamically observe the changes in the level of personal mastery of patients with chronic heart failure, pay more attention to the elderly and patients with poor heart function according to the influencing factors, and encourage active responses to improve the level of personal mastery of patients with heart failure.Keywords: chronic heart failure, the personal mastery, positive coping style, negative coping style, quality of life

Yiming Huang,1,&ast; Xinran Wang,1,&ast; Wenjing Li,1,&ast; Feng Yue,1,2 Miao Wang,1 Feifan Zhou1,2 1State Key Laboratory of Digital Medical Engineering, School of Biomedical Engineering, Hainan University, Sanya, People’s Republic of China; 2One Health Institute, Hainan University, Haikou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Miao Wang; Feifan Zhou, Email wangm@hainanu.edu.cn; zhouff@hainanu.edu.cnPurpose: To avoid the biotoxicity and poor bioavailability of deferoxamine mesylate (DFO), an iron chelation for the treatment of Parkinson’s disease (PD), a self-oriented DFO nanoparticle functionalized with Exendin-4 was developed, which can be targeted delivered into the lesion brain area to achieve synergistic effects against PD by iron chelation and inflammatory suppression.Methods: The self-oriented DFO nanoparticles (Ex-4@DFO NPs) were synthesized by double emulsion technique, and characterized in terms of the particle size, morphology and DFO encapsulation efficiency. The cellular internalization, biocompatibility and cytoprotection of NPs were assessed on BV-2 and SH-SY5Y cells. The brain targeting and therapeutic effect of NPs were investigated in MPTP-induced PD mice by near-infrared II fluorescence imaging and immunofluorescence staining, as well as mobility behavioral tests.Results: Ex-4@DFO NPs with a particle size of about 100 nm, showed great biocompatibility and cytoprotection in vitro, which inhibited the decrease of mitochondrial membrane potential of SH-SY5Y cells and the release of inflammatory factors of BV-2 cells. In MPTP-induced PD mice, Ex-4@DFO NPs could penetrate the BBB into brain, and significantly mitigate the loss of dopaminergic neurons and inflammation in the substantia nigra, finally alleviate the mobility deficits.Conclusion: This self-oriented nanosystem not only improved the biocompatibility of DFO, but also enhanced therapeutic effects synergistically by ameliorating neuronal damage and neuroinflammation, showing a potential therapeutic strategy for PD. Keywords: Parkinson’s disease, deferoxamine mesylate, Exendin-4, nanoparticle system, brain targeting

Xinyang Nie,1– 3,&ast; Jian Liu,1,2,&ast; Daohan Wang,1,2,&ast; Chuan Li,1,2 Yuxin Teng,1,2 Zhufeng Li,1,2 Yangpu Jia,1,2 Peiyao Wang,1,2 Jingyu Deng,2,3 Weidong Li,1,2 Li Lu1,2 1Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Lu; Weidong Li, Department of General surgery, Tianjin Medical University General Hospital, 154, Anshan Road, Heping District, Tianjin, 300052, People’s Republic of China, Email luli_1989@126.com; tjmughgs_lwd@163.comBackground: Cisplatin (DDP) resistance in gastric cancer (GC) is likely to come from gastric cancer stem cells (GCSC). It is a new idea to study the mechanism of the DDP-resistance in GCSC from miRNA.Materials and Methods: CD44+ GCSCs and CD44- control cells were constructed based on the HGC27 gastric cancer cell line. DDP sensitivities in CD44+ and CD44- cells were detected via CCK-8 assay. The differential expression of miR-21-5p in these cell lines was detected by RT‒qPCR. The expression levels of downstream TGF-β 2, SMAD2 and SMAD3 were determined through RT‒PCR and Western blotting. A luciferase assay was used to detect the relationship between miR-21-5p and TGFB2, and the TCGA database, clinical data from our centre, and vivo experiment were used for validation. Finally, we knocked down miR-21-5p to detect changes in cisplatin resistance in GCSCs and to verify changes in the levels of downstream pathways in GCSCs.Results: CD44+ GCSCs induced cisplatin resistance compared with CD44- cells. miR-21-5p was highly expressed in GCSCs, and the TGF-β 2/SMAD pathway was also highly expressed. TGFB2 was proven to be a downstream target gene of miR-21-5p and had a positive relationship with it in phenotype. After knockdown of miR-21-5p, the TGF-β 2/SMAD pathway was also inhibited, and the resistance of GCSCs to cisplatin was specifically decreased.Conclusion: MiR-21-5p promotes cisplatin resistance in gastric cancer stem cells by regulating the TGF-β 2/SMAD signalling pathway.Keywords: miR-21-5p, cisplatin resistance, GCSCs, TGF-β 2 pathway

Min Zhao,1 Liuxiang Feng,2 Wenhua Li3 1School of Medicine, Lijiang University of Culture and Tourism, Lijiang, Yunnan, 674100, People’s Republic of China; 2People’s Hospital of Yulong Naxi Autonomous County of Lijiang City, Lijiang, Yunnan, 674112, People’s Republic of China; 3School of Medicine, Xizang Minzu University, Xianyang Shaanxi, 712082, People’s Republic of ChinaCorrespondence: Min Zhao, School of Medicine, Lijiang University of Culture and Tourism, Lijiang, Yunnan, 674100, People’s Republic of China, Email 1398606492@qq.comObjective: To employee network pharmacology to predict the components and pathways of SanQi-DanShen (SQDS) in treating coronary heart disease, followed by in vitro experiments to validate the molecular mechanism of SQDS in treating coronary heart disease.Methods: We sourced the active ingredients and targets of Panax notoginseng and Danshen from the Traditional Chinese Medicine Systems Pharmacology database. Coronary heart disease related genes were retrieved from the OMIM, Genecards, and Therapeutic Target databases. Using Cytoscape 3.7.2 software, we constructed a network diagram illustrating the components and targets of SQDS. The associated targets were then imported into the STRING database to build a protein-protein interaction network. The Metascape database and WeChat software were utilized for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Lastly, we performed molecular docking between the key components and related targets using AutoDock Vina. To validate the potential mechanism of SQDS in treating coronary heart disease, we established an acute coronary heart disease rat model via tail vein injection of pituitrin.Results: Network pharmacology analysis revealed that 65 active ingredients and 167 targets of SQDS are implicated in the treatment of coronary heart disease. The key targets identified include AKT1, TNF, TP53, IL6, and VEGFA. Notably, the PI3K/AKT signaling pathway emerged as the primary pathway. Furthermore, animal experiments showed that, compared to the model group, SQDS significantly reduced levels of TNF-α, IL-6, Bax, and cardiac troponin I, while increasing Bcl-2 content. It also notably suppressed the expression of p-PI3K and p-AKT, thereby offering protection to myocardial tissue.Conclusion: Through the integrated approach of network pharmacology and molecular docking, we have established that SQDS exerts a multi-component, multi-target, and multi-pathway synergistic therapeutic effect on coronary heart disease. Its mechanism may involve the inhibition of the PI3K/AKT signaling pathway and the reduction of inflammatory factor expression.Keywords: SQDS, cardiac troponin I, PI3K/AKT signaling pathway, coronary heart disease, experiment validation

Linsheng Wang,1,&ast; Yang Xu,2,&ast; Xudong Zhang,1 Jiahui Ding,1 Jingkun Jin,1 Jing Zong,1 Fangfang Li,1 Weidong Qian,3 Wenhua Li1,4 1Institute of Cardiovascular Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Cardiology, Xuzhou Central Hospital, Xuzhou, Jiangsu, People’s Republic of China; 3Department of Cardiology, Wujin Affiliated Hospital of Nanjing University of Chinese Medicine, Changzhou, Jiangsu, People’s Republic of China; 4Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weidong Qian, Department of Cardiology, Wujin Affiliated Hospital of Nanjing University of Chinese Medicine, Changzhou, Jiangsu, People’s Republic of China, Email qwd213161@163.com Wenhua Li, Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China, Email xzwenhua0202@163.comBackground: Contrast-induced acute kidney injury (CI-AKI) refers to the acute renal dysfunction caused by the injection of contrast agents. CI-AKI is currently a common complication after percutaneous coronary intervention (PCI).Objective: To investigate the predictive value of the combined systemic inflammatory index (SII) and urate/high-density lipoprotein cholesterol ratio (UHR) for CI-AKI after PCI in patients with AMI.Methods: A total of 1222 patients with AMI who underwent PCI were randomly divided into a training group and a validation group in an 8:2 ratio. According to the definition of CI-AKI diagnostic criteria, the training group was divided into CI-AKI group and non-CI-AKI group. Collect patient’s blood and biochemical data, then calculate SII and UHR. The risk factors for CI-AKI were identified using LASSO and multivariate logistic regression analyses. A predictive column was created by using R language.Evaluate the predictive value of SII, UHR and their combination for CI-AKI after PCI using the area under the ROC curve (AUC).Results: Diabetes, Cystatin C, Diuretics, UHR, and LnSII were independent risk factors for CI-AKI in AMI patients after PCI. The ROC curve showed that the AUC of UHR and SII combined for predicting CI-AKI in AMI patients after PCI was 0.761 (95% CI: 0.709– 0.812), with a sensitivity of 65.20% and a specificity of 76.70%, which was better than the prediction by either factor alone.Conclusion: High SII and high UHR are risk factors for AMI, and their combination can improve the accuracy of predicting CI-AKI in AMI patients after PCI.The prognosis of CI-AKI in AMI patients is worse than in the general population.Keywords: serum uric acid, high-density lipoprotein cholesterol, neutrophils, lymphocytes, systemic immune-inflammatory index, contrast-induced acute kidney injury

Ling Zhao,1– 3,&ast; Shichao Li,1,2,4,&ast; Xiaoyu Wang,1,2 Lingyan Zhang,1,2 Jingge Zhang,1,2 Xiyun Liu,1,2 Yuyan Hu,1,2 Xiaohui Xian,1,2 Feng Zhang,5 Wenbin Li,1,2 Min Zhang1,2,6 1Department of Pathophysiology, Hebei Medical University, Shijiazhuang, Hebei Province, 050017, People’s Republic of China; 2Hebei Key Laboratory of Critical Disease Mechanism and Intervention, Shijiazhuang, Hebei Province, 050017, People’s Republic of China; 3Department of Obstetrics, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050000, People’s Republic of China; 4Experimental Diagnostic Center for Infectious Diseases, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050000, People’s Republic of China; 5Department of Rehabilitation Medicine, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 6The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, Hebei Province, 050017, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Zhang, Department of Pathophysiology, Key Laboratory of Critical Disease Mechanism and intervention of Hebei Province, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, Hebei, 050017, People’s Republic of China, Email hebmuzhangmin@hebmu.edu.cnBackground: Obesity is recognized as a primary risk factor for cerebral ischemia, which has shown a significant increase in its incidence among obese patients. The exact mechanism by which obesity exacerbates cerebral ischemic injury is not fully understood though. The present study validated the hypothesis that obesity mediates pyroptosis by the AGEs/RAGE signaling pathway to exacerbate cerebral ischemic injury.Methods: Leptin receptor knockout (Lepr−/−) rats were used in this study to construct an obesity model, and the middle cerebral artery occlusion (MCAO) models of ischemic stroke were established in Lepr−/− obese rats and their wild-type (WT) littermates respectively. Zea-Longa score, TTC and H&E staining were utilized to evaluate the neurological impairment. Western Blot, immunohistochemistry, and immunofluorescence were used to detect protein expressions. Transmission electron microscopy was used to observe the pores in the neuronal cell membrane in the ischemic penumbra cortex.Results: Compared with WT littermates, Lepr−/− obese rats exhibited exacerbated neuronal injury after MCAO, with higher expressions of NLRP3 inflammasome and pyroptosis-related proteins in the cortical tissue of the penumbra. Moreover, more GSDMD pores were observed on the neuronal cell membranes of Lepr−/− obese rats according to the electron microscopy. Inhibition of NLRP3 inflammasome expression with MCC950 inhibited neuronal pyroptosis after cerebral ischemia in Lepr−/− obese rats, thus reducing neuronal injury. We also found that compared with WT littermates, the levels of AGEs and RAGE in the cortex of Lepr−/− obese rats are significantly higher, with further increase after cerebral ischemia. Inhibition of AGEs/RAGE signaling pathway with FPS-ZM1 reduced the NLRP3 inflammasome-mediated neuronal pyroptosis in Lepr−/− obese rats, thereby mitigating the neuronal damage after cerebral ischemia.Conclusion: The AGEs/RAGE signaling pathway is involved in the exacerbation of cerebral ischemic injury in Lepr−/− obese rats via regulating NLRP3-mediated neuronal pyroptosis. Keywords: MCAO, neuronal pyroptosis, NLRP3, Lepr−/− obese rats, AGEs/RAGE signaling pathway

Liping Shen, Jiangsheng Yang, Zufu Zhu, Weizhang Li, Junyou Cui, Lingyun Gu Department of Neurology, Jiangyin Hospital Affiliated to Nantong University, Jiangyin, Jiangsu, People’s Republic of ChinaCorrespondence: Lingyun Gu, Department of Neurology, Jiangyin Hospital Affiliated to Nantong University, 163 Shoushan Road, Jiangyin, Jiangsu, 214400, People’s Republic of China, Tel/Fax +86 13915313817, Email lygneuro@163.comPurpose: The study aimed to investigate the correlation between baseline serum levels of high mobility group box 1 (HMGB1) and the recurrence of acute ischemic stroke (AIS).Patients and Methods: A total of 544 AIS patients were enrolled and followed up monthly. Serum HMGB1 levels were measured using enzyme-linked immunosorbent assay (ELISA). The primary endpoint was the first recurrence of AIS.Results: During a median follow-up period of 43 months, 62 of the 544 AIS patients experienced a recurrence. Both HMGB1 levels and national institute of health stroke scale (NIHSS) scores were significantly higher in the recurrence group compared to the no-recurrence group (p< 0.05). According to the receiver operating characteristic curve analysis, the combination (0.855, 95% CI: 0.800– 0.911) of HMGB1 (0.745, 95% CI: 0.663– 0.826) and NIHSS (0.822, 95% CI: 0.758– 0.886) had a higher value for predicting AIS recurrence than either of them (p< 0.05). Kaplan-Meier analyses demonstrated that the cumulative survival without AIS recurrence was significantly lower in patients in the high HMGB1 level group than in the low HMGB1 level group (p< 0.05). The multifactorial Cox analyses indicated that elevated baseline serum HMGB1 levels (HR: 7.489, 95% CI:4.383– 12.795) were a highly effective predictor of recurrence in AIS.Conclusion: Elevated baseline serum HMGB1 levels were found to be a highly effective predictor of recurrence in AIS.Keywords: high mobility group box 1, acute ischemic stroke, recurrence

Fan Zhang,1– 3 Wenjian Li1,4 1Changzhou Clinical College, Xuzhou Medical University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Endocrinology, Changzhou Third People’s Hospital, Changzhou, Jiangsu, People’s Republic of China; 3Department of Clinical Nutrition, Changzhou Third People’s Hospital, Changzhou, Jiangsu, People’s Republic of China; 4Department of Urology, Changzhou Third People’s Hospital, Changzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Wenjian Li, Department of Urology, Changzhou Third People’s Hospital, 300 Lanling North Road, Changzhou, Jiangsu, 213001, People’s Republic of China, Tel +86-0519-82009011, Email 760020240117@xzhmu.edu.cnObjective: This study examined the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and urinary incontinence in adult women and evaluated the potential contribution of the fatty liver index (FLI) in this context.Methods: The study utilized data from the National Health and Nutrition Examination Survey (NHANES) database, spanning from 2001 to 2018. The study included 17,221 adult female participants. Individuals exhibiting FLI values of 60 or greater were diagnosed with hepatic steatosis. Incontinence type and MASLD status were evaluated by analyzing questionnaire data and calculating the FLI. Logistic regression models were employed to examine the correlation between FLI, MASLD, and urinary incontinence, with potential confounding variables controlled through multivariate adjustment models. Furthermore, restricted cubic spline curve (RCS) modeling and subgroup analysis were employed to elucidate the relationship between variables further.Results: The median age of participants in the MASLD group was higher than that of the non-MASLD group (53 vs 46 years, P < 0.001). The findings indicated a positive association between FLI and MASLD and the risk of urinary incontinence. Specifically, the risk of stress urinary incontinence (SUI), urgency urinary incontinence (UUI), and mixed urinary incontinence (MUI) all increased significantly with increasing quartiles of FLI (OR 2.44, 1.91, 2.30, respectively, P < 0.001). In the multivariate-adjusted model, SUI, UUI, and MUI risk was 76%, 50%, and 69% higher in patients with MASLD than those without MASLD. RCS analysis demonstrated a significant nonlinear positive correlation between FLI and the risk of SUI, UUI, and MUI, respectively.Conclusion: This study’s findings indicate a significant association between MASLD and the risk of developing urinary incontinence. Additionally, the results suggest that FLI and MASLD may act as independent risk factors for urinary incontinence.Keywords: metabolic dysfunction-associated steatotic liver disease, urinary incontinence, fatty liver index, adult women, correlation study

Yichen Wang,1,&ast; Yibo Zhang,1,&ast; Qun Wang,1 Wenhui Li,1 Dake Shi,1 Yumin Xu1,2 1Department of Hospital Infection Management, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yumin Xu, Email xym121@163.comPurpose: Hospital-acquired infections (HAIs) caused by multidrug-resistant organisms (MDROs) pose a significant challenge to healthcare systems. The present study aimed to evaluate the impact of the infection policy to COVID-19 on the incidence of HAIs caused by MDROs.Methods: We conducted an eight-years retrospective analysis at a hospital in Shanghai, China. Bloodstream, sputum, and urinary tract cultures of MDROs obtained 48h after admission were collected monthly from January 2016 to Dec 2023. Occupied bed days (OBDs) were used to generate monthly HAI incidences per 10,000 OBDs. The study period was divided into pre-control, in-control, and post-control cohorts, in January 2020 and January 2022. The incidence was compared using interrupted time-series regression.Results: In total, 6763 MDRO cultures were identified, comprising 1058 bloodstream, 4581 sputum, and 1124 urine cultures derived from 4549 patients. The incidence rates of all HAIs were 8.68 per 10,000 OBDs in the pre-control cohort, 9.76 per 10,000 OBDs in the in-control cohort and 12.58 per 10,000 OBDs in the post-control cohorts, respectively. A downward trend in the incidence of HAI was observed in the post-control cohort (p< 0.05).Conclusion: This study demonstrates that while the COVID-19 pandemic poses a significant challenge to infection control within hospitals, it provides a unique opportunity to enhance infection control measures and evaluate their effectiveness. In addition, these findings highlight the need for more targeted prevention and control strategies against different pathogens in future epidemics.Keywords: hospital required infection, multidrug-resistant organism, infection control, policy, Covid-19, surveillance

Tianqing Cao,1,&ast; Fei Liu,2,&ast; Yan Yao,2 Danghong Sun,2 Rong Wang,3 Junxia Cao,3 Jie Meng,2 Ling Zhang,4 Weiming Li1 1Shanghai Tenth People’s Hospital, Clinical Medical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Cardiology, Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu, People’s Republic of China; 3Department of Pulmonology, Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu, People’s Republic of China; 4Department of Nursing, Changshu No.2 People’s Hospital/Affiliated Changshu Hospital of Nantong University, Changshu, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiming Li; Ling Zhang, Email 18917683469@189.cn; nancy120312@163.comObjective: Current scoring systems for short-term prognosis in patients with acute myocardial infarction (AMI) lack coverage of risk factors and have limitations in risk stratification. The aim of this study was to develop a novel assessment system based on laboratory indicators and frailty quantification to better infer short-term prognosis and risk indication in patients with AMI.Methods: A total of 365 patients with MI from January 2022 to June 2023 in Northern Jiangsu Province Hospital were included. The primary endpoint was all-cause mortality and major adverse cardiac events (MACE) during follow-up. A novel scoring model ranging from 0 to 12 was constructed, and the predictive ability of this scoring system was evaluated using the area under the receiver operating characteristic curve (AUC).Results: During follow-up, 68 patients experienced MACE. Five scoring indicators were selected through multivariate logistic regression analysis, resulting in a composite score with an AUC of 0.925, demonstrating good prognostic accuracy.Conclusion: The novel prognostic assessment system, which integrates age, Stress Hyperglycemia Ratio (SHR), Neutrophil to Lymphocyte Ratio (NLR), lactate, and frailty score, exhibits good predictive value for short-term MACE in patients with acute myocardial infarction and may enable more accurate risk classification for future use in MI patient risk management.Keywords: myocardial infarction, frailty index, major adverse cardiac events, prognosis, cohort study

Danwei Zhang,1 Yating Zeng,1 Bin Sun,2 Wei Li,2 Wenjuan Liu,2 Haiyan Gao,2 Yibing Zhu,2 Haibo Li,2,&ast; Qiang Chen1,&ast; 1Department of Cardiac Surgery, Fujian Children’s Hospital (Fujian Branch of Shanghai Children’s Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 2Division of Birth Cohort Study, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Chen, Department of Cardiac Surgery, Fujian Children’s Hospital (Fujian Branch of Shanghai Children’s Medical Center), College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No. 966 Hengyu Road, Jinan District, Fuzhou, 350014, People’s Republic of China, Email chenqiang2228@163.com Haibo Li, Division of Birth Cohort Study, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, No. 18 Daoshan Road, Gulou District, Fuzhou, 350001, People’s Republic of China, Email haiboli89@163.comPurpose: Gestational diabetes mellitus (GDM) is a prevalent complication during pregnancy. This study aimed to explore the associations between inflammatory indices during pregnancy and the development of GDM.Methods: Data from the Fujian Birth Cohort Study between March 2019 and December 2022 were used. Participants who delivered a live-born singleton were included and categorized into GDM and non-GDM groups. Two inflammatory indices, the systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI), were calculated for each trimester of pregnancy via hematological parameters from complete blood count tests. The distributions of inflammatory indicators across trimesters were compared between the GDM and non-GDM groups. Additionally, multivariable logistic regression models were employed to investigate the associations between inflammatory indices and the incidence of GDM.Results: A total of 17297 participants were included, 21.2% of whom were diagnosed with GDM. In the first trimester, the median SIIs for the GDM and non-GDM groups were 817.7× 109/L and 756.9× 109/L, respectively, whereas the median SIRIs were 1.6× 109/L and 1.5× 109/L, respectively. In both groups, the SII increased to its peak in the second trimester before declining, whereas the SIRI progressively increased throughout pregnancy. The SII and SIRI were greater in the GDM group than in the non-GDM group during the first two trimesters but lower in the third trimester. Nonlinear positive associations between first-trimester SII and SIRI levels and GDM were observed, with extreme quartile odds ratios of 1.32 (95% CI: 1.19, 1.48) and 1.39 (95% CI: 1.24, 1.55), respectively.Conclusion: The SII and SIRI increased and reached their peak values in the second and third trimesters of pregnancy, respectively. Elevated levels of the SII and SIRI in early pregnancy were linked to an increased risk of GDM, suggesting their potential utility as screening tools for GDM.Keywords: gestational diabetes mellitus, GDM, systemic immune-inflammation index, SII, systemic inflammatory response index, SIRI

Lijie Ren,1 Ye Chen,2 Xianguo Han,3 Ziyi Chen,2 Zhi Wang,4 Wenxiao Li,2 Hongyuan Chen2 1Mental Health Center, Shanghai Customs University, Shanghai, People’s Republic of China; 2School of Customs and Public Administration, Shanghai Customs University, Shanghai, People’s Republic of China; 3School of Psychology, Shanghai Normal University, Shanghai, People’s Republic of China; 4School of Customs and Public Economics, Shanghai Customs University, Shanghai, People’s Republic of ChinaCorrespondence: Xianguo Han, School of Psychology, Shanghai Normal University, 100 Guilin Street, Xuhui District, Shanghai, 200234, People’s Republic of China, Email hanxg.psy@aliyun.comBackground: Suicide is a global public health issue. This study examined the role of COVID-19 burnout and reappraisal in suicidal ideation caused by depressive symptoms among Chinese college students.Methods: 587 students (261 boys, Mage = 19.53, SD = 1.42) were assessed using the Short Depression-Happiness Scale (SDHS), Positive and Negative Suicide Ideation (PANSI) inventory, and Emotion Regulation Scale (ERS).Results: Correlation analysis indicated depressive symptoms were negatively correlated with reappraisal and positively correlated with suicidal ideation and COVID-19 burnout. Reappraisal was negatively correlated with suicidal ideation and COVID-19 burnout. The moderated mediation model showed COVID-19 burnout enhanced the direct effect of depressive symptoms on suicidal ideation and indirectly enhanced this effect by weakening the protective role of reappraisal.Conclusion: These finding show that reappraisal acts as a protective factor against suicidal ideation in individuals with depressive symptoms, while COVID-19 burnout exacerbates this effect by weakening reappraisal’s protective role.Keywords: depressive symptoms, suicidal ideation, reappraisal, COVID-19 burnout, moderated mediation model

Haoming Luo,1,2,&ast; Miao Guo,3,4,&ast; Mingxing Li,1 Yueshui Zhao,1 Jing Shen,1 Fukuan Du,1 Yu Chen,1 Shuai Deng,1 Yuhong Sun,1 Li Gu,1 Wanping Li,1 Xiaobing Li,1 Meijuan Chen,1 Zhangang Xiao,1,5,6 Shengpeng Wang,3,4 Xu Wu1,7 1Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China; 2Department of Pharmacy, Three Gorges University Hospital of Traditional Chinese Medicine & Yichang Hospital of Traditional Chinese Medicine, Yichang, Hubei, 443003, People’s Republic of China; 3State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China; 4Macao Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China; 5Department of Pharmacy, Gulin County Hospital of Traditional Chinese Medicine, Luzhou, Sichuan, 646500, People’s Republic of China; 6School of Pharmacy, Sichuan College of Traditional Chinese Medicine, Mianyang, Sichuan, 621000, People’s Republic of China; 7Department of Paediatric Care, Luzhou People’s Hospital, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengpeng Wang, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China, Email swang@um.edu.mo Xu Wu, Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646100, People’s Republic of China, Email wuxulz@swmu.edu.cnIntroduction: Rhodiola species have been utilized as functional foods in Asia and Europe for promoting health. Research has demonstrated that Rhodiola has the potential to alleviate inflammatory bowel disease (IBD) in animal models. However, the specific active components and the underlying mechanism for ameliorating intestinal damage remain unclear. This study aims to explore the relieving effect of Rosavin (Rov), a known active constituent of Rhodiola, in IBD and the regulatory mechanisms.Methods: The therapeutic effect of Rov was evaluated using a murine model of acute colitis induced by dextran sulfate sodium salt (DSS). Inflammatory cytokines and neutrophil activation markers were measured by corresponding kits. Immunohistochemistry, immunofluorescence, TUNEL, and EdU assays were applied to investigate the tight conjunction proteins expression, epithelial marker expression, number of apoptotic cells, and epithelial proliferation, respectively. The protection effect of Rov on gut epithelial injury was assessed using TNF-α-induced intestinal organoids. Additinally, RNA sequencing was applied to observe the genetic alteration profile in these intestinal organoids.Results: Oral administration of Rov significantly attenuated weight loss and restored colon length in mice. Notably, Rov treatment led to decreased levels of pro-inflammatory cytokines and neutrophil activation markers while increasing anti-inflammatory factors. Importantly, Rov restored intestinal despair by increasing the number of Lgr5+ stem cells, Lyz1+ Paneth cells and Muc2+ goblet cells in intestines of colitis mice, displaying reduced epithelial apoptosis and recovered barrier function. In TNF-α-induced intestinal organoids, Rov facilitated epithelial cell differentiation and protected against TNF-α-induced damage. RNA sequencing revealed upregulation in the gene expression associated with epithelial cells (including Lgr5+, Lyz1+ and Muc2+ cells) proliferation and defensin secretion, unveiling the protective mechanisms of Rov on the intestinal epithelial barrier.Discussion: Rov holds potential as a natural prophylactic agent against IBD, with its protective action on the intestinal epithelium being crucial for its therapeutic efficacy. Keywords: rosavin, colitis, inflammatory bowel disease, organoid, intestinal stem cell

Wenlu Li,1,2,&ast; Yaolin Gong,1,2,&ast; Jing Zhang,1,2 Jiong Liu,1,2 Jiali Li,1,2 Shaozhi Fu,3 Wen Xiu Ren,1,2 Jian Shu1,2 1Department of Radiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Xiu Ren; Jian Shu, Department of Radiology, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping St, Jiangyang District, Luzhou, Sichuan, 646000, People’s Republic of China, Email xrenwenxiux@swmu.edu.cn; shujiannc@swmu.edu.cnIntroduction: Targeting, imaging, and treating tumors represent major clinical challenges. Developing effective theranostic agents to address these issues is an urgent need.Methods: We introduce an “all-in-one” tumor-targeted theranostic platform using CuFeSe2-based composite nanoparticles (CuFeSe2@PA) for magnetic resonance (MR) and computed tomography (CT) dual model imaging-guided hyperthermia tumor ablation. Plerixafor (AMD3100) is bonded to the surface of CuFeSe2 as a targeting unit. Due to the robust interaction between AMD3100 and the overexpressed Chemokine CXC type receptor 4 (CXCR4) on the membrane of 4T1 cancer cells, CuFeSe2@PA specifically recognizes 4T1 cancer cells, enriching the tumor region.Results: CuFeSe2@PA serves as a contrast agent for T2-weighted MR imaging (relaxivity value of 1.61 mM− 1 s− 1) and CT imaging. Moreover, it effectively suppresses tumor growth through photothermal therapy (PTT) owing to its high photothermal conversion capability and stability, with minimized side effects demonstrated both in vitro and in vivo.Discussion: CuFeSe2@PA nanoparticles show potential as dual-mode imaging contrast agents for MR and CT and provide an effective means of tumor treatment through photothermal therapy. The surface modification with Plerixafor enhances the targeting ability of the nanoparticles, performing more significant efficacy and biocompatibility in the 4T1 cancer cell model. The study demonstrates that CuFeSe2@PA is a promising multifunctional theranostic platform with clinical application potential. Keywords: tumor targeting, photothermal therapy, dual model imaging, theranostic platform, chemokine cxc type receptor 4

Fan Zhang,1,2 Wenjian Li3 1Department of Endocrinology, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Clinical Nutrition, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of China; 3Department of Urology, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Wenjian Li, Department of Urology, Changzhou Third People’s Hospital, Changzhou Medical Center, Nanjing Medical University, 300 Lanling North Road, Changzhou, Jiangsu, 213001, People’s Republic of China, Tel +86-519-82009011, Email bolite@163.comAbstract: This article reviews the mechanisms and prevention strategies associated with vitamin D and sarcopenia in older adults. As a geriatric syndrome, sarcopenia is defined by a notable decline in skeletal muscle mass and strength, which increases the risk of adverse health outcomes such as falls and fractures. Vitamin D, an essential fat-soluble vitamin, is pivotal in skeletal muscle health. It affects muscle function through various mechanisms, including regulating calcium and phosphorus metabolism, promoting muscle protein synthesis, and modulation of muscle cell proliferation and differentiation. A deficiency in vitamin D has been identified as a significant risk factor for the development of sarcopenia in older adults. Many studies have demonstrated that low serum vitamin D levels are significantly associated with an increased risk of sarcopenia. While there is inconsistency in the findings, most studies support the importance of vitamin D in maintaining skeletal muscle health. Vitamin D influences the onset and progression of sarcopenia through various pathways, including the promotion of muscle protein synthesis, the regulation of mitochondrial function, and the modulation of immune and inflammatory responses. Regarding the prevention and treatment of sarcopenia, a combination of nutritional, exercise, and pharmacological interventions is recommended. Further research should be conducted to elucidate the molecular mechanism of vitamin D in sarcopenia, to study genes related to sarcopenia, to perform large-scale clinical trials, to investigate special populations, and to examine the combined application of vitamin D with other nutrients or drugs. A comprehensive investigation of the interconnection between vitamin D and sarcopenia will furnish a novel scientific foundation and productive strategies for preventing and treating sarcopenia. This, in turn, will enhance the senior people’s quality of life and health.Keywords: vitamin D, sarcopenia, senior people, pathogenesis, comprehensive prevention and treatment strategies

You Jiang,1,2 Wenbo Li,1,2 Jun Zhang,1 Kun Liu,1 Yuee Wu,3 Zhengguang Wang1 1Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China; 2Department of General Surgery, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China; 3Department of Electrocardiogram Diagnosis, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230060, People’s Republic of ChinaCorrespondence: Zhengguang Wang, Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China, Email wangzhengguang@ahmu.edu.cnBackground: Cysteine desulfurase (NFS1) is closely associated with the occurrence and development of human tumors, but its relationship with the prognosis and immunity of gastric cancer (GC) patients remains unclear.Methods: To study the relationship between NFS1 and GC, GC-related data of TCGA were downloaded and analyzed. At the same time, Tumor Immune Estimation Resource (TIMER) and Kaplan‒Meier Plotter were used for relevant online analysis. Clinical samples were collected for immunohistochemical testing to validate the results.Results: The mRNA and protein levels of NFS1 in GC tissues were significantly higher than those in normal tissues. In terms of the operating characteristic curve (ROC), the area under the curve (AUC) was 0.793, indicating that NFS1 had a high diagnostic value for GC. Further analysis showed that NFS1 expression was highly correlated with the depth of tumor invasion, lymph node metastasis, and tumor stage. Survival analysis showed that patients with high expression of NFS1 had a poorer prognosis, and NFS1 was an independent risk factor. Enrichment analysis by GO, KEGG, and GSEA showed that NFS1 was enriched in immune-related pathways. The expression of NFS1 was significantly positively correlated with the proportion of macrophages M0 and plasma cells but negatively correlated with the proportion of B cells memory, monocytes, and mast cells resting. In addition, NFS1 expression was significantly correlated with TMB levels and responses to immunotherapy.Conclusion: Our results suggest that NFS1 may be a potential biomarker for the diagnosis and prediction of prognosis and immunotherapy efficacy in GC.Keywords: NFS1, gastric cancer, prognostic biomarker, immune infiltration

Shanshan Chen,1,2 Youjia Duan,2 Yongchao Zhang,2 Long Cheng,2 Liang Cai,2 Xiaopu Hou,2 Xiaojun Wang,3 Wei Li1,2 1Cancer Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Integrated Traditional Chinese and Western Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Wei Li, Cancer Center, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China, Email weili8989@ccmu.edu.cn Xiaojun Wang, Department of Integrated Traditional Chinese and Western Medicine, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China, Email w_xiaojun@ccmu.edu.cnPurpose: To determine the effect of aspirin on hepatocellular carcinoma (HCC) recurrence and survival after thermal ablation.Methods: A retrospective analysis was performed to evaluate the efficacy and safety of aspirin in combination with thermal ablation. The clinical data were collected for the enrolled patients. Progression-free survival (PFS), overall survival (OS), and adverse events were analyzed.Results: A total of 174 patients with HCC were enrolled. The median PFS was 11.1 (95% confidence interval [CI]: 8.1− 14.0) months for patients who took aspirin and 8.6 (95% CI: 5.5− 11.8) months for patients who did not take aspirin. The median OS of patients in the aspirin group was 76.7 (95% CI: 58.1− 95.3) months and that in the non-aspirin group was 53.5 (95% CI: 42.7− 64.3) months. In patients with non-viral HCC, OS was significantly better for the aspirin group (P = 0.03) after ablation. The PFS of patients who underwent ablation alone in the aspirin group was obviously superior to that of patients in the non-aspirin group (P = 0.002). Stratified Cox regression analysis demonstrated that aspirin use after ablation might be a protective factor in specific HCC patient subgroups. The incidence of major adverse events did not significantly differ between the two groups.Conclusion: Low-dose aspirin use was associated with better OS in patients with non-viral HCC after thermal ablation. In patients who received thermal ablation alone, the administration of low-dose aspirin could improve PFS. Aspirin use might be a protective factor in some patients after ablation.Keywords: thermal ablation, aspirin, hepatocellular carcinoma, survival analysis, retrospective study

Wenyu Li,1 Yanqiu Hou,1 Jiayu An,1 Linxuan Chen,1 Shan Lu1,2 1School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Research Centre for Rural Health Service, Key Research Institute of Humanities & Social Sciences of Hubei Provincial Department of Education, Wuhan, People’s Republic of ChinaCorrespondence: Shan Lu, School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Hang Kong Road 13, Wuhan, 430030, People’s Republic of China, Tel +86 15827079650, Email shanlu@hust.edu.cnPurpose: The objective of this study was to explore the connection between family doctor contract services and preventable hospitalizations. Additionally, we sought to examine the role of primary health care quality as a mediating factor in the link between family doctor contract services and preventable hospitalizations among patients with hypertension.Patients and Methods: This cross-sectional study was performed in Dangyang (Hubei Province, Central China) and Xishui (Guizhou Province, Western China) counties in July–August 2023. Participants comprised 625 patients selected via a multi-stage sampling method. Causal mediation analysis was conducted to explore the effect of family doctor contract services on preventable hospitalizations and the mediating effect of primary healthcare quality on this relationship.Results: Utilization rate of family doctor contract services of hypertensive patients was 58.6%, score of primary health service quality was 70.75 and incidence of preventable hospitalizations was 28.2%. Amongst hypertensive patients, utilization of family doctor contract services decreased the occurrence of preventable hospitalizations, with a total effect of − 0.22 (p < 0.001). Primary healthcare quality mediates the association, with a mediate effect of − 0.05 (p < 0.001), explaining 22.73% of the total effect.Conclusion: Improving the utilization of family doctor contract services and primary healthcare quality may result in lower rates of preventable hospitalizations amongst hypertensive patients.Keywords: family doctor contract services, preventable hospitalizations, primary healthcare quality, hypertension, mediation analysis

Junhua Zhu, Yue Zhuang, Wenjing Li School of Safety Science and Emergency Management, Wuhan University of Technology, Wuhan, People’s Republic of ChinaCorrespondence: Yue Zhuang, Email zhuangyue@whut.edu.cnPurpose: The use of multi-source precursor data to predict the epidemic risk level would aid in the early and timely identification of the epidemic risk of infectious diseases. To achieve this, a new comprehensive big data fusion assessment method must be developed.Methods: With the help of the Functional Resonance Analysis Method (FRAM) model, this paper proposes a risk portrait for the whole process of a pandemic spreading. Using medical, human behaviour, internet and geo-meteorological data, a hierarchical multi-source dataset was developed with three function module tags, ie, Basic Risk Factors (BRF), the Spread of Epidemic Threats (SET) and Risk Influencing Factors (RIF).Results: Using the dynamic functional network diagram of the risk assessment functional module, the FRAM portrait was applied to pandemic case analysis in Wuhan in 2020. This new-format FRAM portrait model offers a potential early and rapid risk assessment method that could be applied in future acute public health events.Keywords: epidemic risk, FRAM, model, big data portrait

Maoliang Tian,1,&ast; Wenqiang Li,1,&ast; Xiaoyu He,2 Qian He,3 Qian Huang,4 Zhiping Deng1 1Zigong First People’s Hospital, Zigong City, Sichuan Province, 643000, People’s Republic of China; 2North Sichuan Medical College, Nanchong, Sichuan Province, 637000, People’s Republic of China; 3West China Second Hospital of Sichuan University, Chengdu, Sichuan Province, 610044, People’s Republic of China; 4Dazhou Dachuan District People’s Hospital (Dazhou Third People’s Hospital), Dazhou, Sichuan Province, 635000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian Huang, Dazhou Dachuan District People’s Hospital (Dazhou Third People’s Hospital), Dazhou, Sichuan Province, 635000, People’s Republic of China, Email hq15196767955@163.com Zhiping Deng, Zigong First People’s Hospital, Zigong City, Sichuan Province, 643000, People’s Republic of China, Email dengzp1016@163.comBackground: In human health, vitamins play a vital role in various metabolic and regulatory processes and in the proper functioning of cells. Currently, the effect of Vitamin E (VE) intake on multiple causes of death in Chronic obstructive pulmonary disease (COPD) patients is unclear. Therefore, this paper aims to investigate the relationship between VE and multiple causes of death in COPD patients, to guide the rationalization of dietary structure and reduce the risk of COPD death.Methods: This study screened patients with COPD aged ≥ 40 years from the National Health and Nutrition Examination Survey (NHANES) database 2008– 2018. Weighted COX regression was used to analyze the association between VE intake and multiple causes of death in COPD. The restricted cubic spline(RCS) is drawn to show their relationship. Finally, we conducted a subgroup analysis for further verification.Results: A total of 1261 participants were included in this study. After adjustment for multiple covariates, VE intake was associated with all-cause death in COPD patients, and chronic lower respiratory disease (CLRD) deaths were linearly associated with cardiovascular disease (CVD) deaths there was no such correlation. Subgroup analyses showed no interaction between subgroups, further validating the robustness of the relationship.Conclusion: In COPD patients, VE intake was negatively associated with all-cause mortality and CLRD death. Higher VE intake reduces the risk of all-cause mortality and CLRD death in COPD patients.Keywords: vitamin E, COPD, CVD, CLRD, COX regression analyses

Mengmeng Yuan,1 Lijun Wu,2 Wen Li,1 Shuwen Li1 1School of Nursing, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Shuwen Li, School of Nursing, Anhui Medical University, No. 15 Feicui Road, Economic and Technological Development District, Hefei, 230601, People’s Republic of China, Email lishuwen@ahmu.edu.cnPurpose: We intended to explore the chain mediation role of resilience and different sources of social support on the relationship between symptom interference and life satisfaction from the patient-reported perspective.Patients and Methods: Two hundred and twenty-six patients after esophagectomy were investigated using four validated scales to estimate the symptom interference, resilience, different sources of social support, and life satisfaction. The chain mediation analysis was conducted using SPSS PROCESS Macro Model 6.Results: Mediation analysis showed that symptom interference indirectly influenced life satisfaction through two significant mediating pathways: (i) resilience (B = − 0.138, 95% CI: − 0.194 to − 0.091); (ii) the chain mediators involving in resilience and family support (B = − 0.049, 95% CI: − 0.073 to − 0.026). Surprisingly, the mediating pathway of family support was not significant.Conclusion: Interventions for resilience and family support could mitigate the adverse effects of symptom interference in patients after esophagectomy, improving life satisfaction. Of these, resilience may be more critical in terms of the utilization of social resources than family support.Keywords: life satisfaction, oesophageal cancer, social support, resilience, symptom interference

Haotian Chen, Juan Zhi, Lei Wang, Zibin Jin, Jin Xu, Fei Xing, Chao Wen, Qianyu Wang, Chunmei Chen, Weiou Li, Ermeng Xu, Jie An, Lingxin Wei Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Lingxin Wei, Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 33 Badachu Road, Shijingshan District, Beijing, 100144, People’s Republic of China, Tel +86 010 85557917, Email weilx3934@sina.comPurpose: Esketamine have anesthetic and analgesic properties. This study aimed to observe the enhancing effect of subanesthetic doses of esketamine (0.15– 0.3 mg/kg/h) with dexmedetomidine and remifentanil during anesthesia for liposuction surgery.Patients and Methods: A total of 155 subjects were randomized with a 1:1 ratio to Group E (esketamine-dexmedetomidine/remifentanil, n=78) or Group C (saline-dexmedetomidine/remifentanil group, n=77). The primary outcome was satisfaction of patient and surgical team with the procedure. The secondary outcomes were the postoperative Athens Insomnia Scale (AIS) and Hospital Anxiety and Depression Scale (HADS) scores, hemodynamic and respiratory changes, drug consumption, adverse event rates, and predictors associated with patient satisfaction.Results: Patient and surgical team satisfaction with the procedure was significantly higher in Group E than in Group C (4.7 ± 0.6 vs 4.2 ± 0.7, P < 0.001; 4.7 ± 0.5 vs 4.4 ± 0.7, P = 0.005). The postoperative AIS (4 [1, 6] vs 5 [2, 9], P = 0.012) and HADS-A (1 [0, 3] vs 2 [0, 6], P = 0.012) scores were significantly lower in Group E than in Group C. Hemodynamic and respiratory parameters were more stable in Group E than in Group C, with the lower opioids consumption of sufentanil (0 [0, 4] vs 5 [2.5, 7.7], P < 0.001) and remifentanil (700 [480, 900] vs 800 [500, 1200], P = 0.023) in Group E compared to Group C. On ordinal logistics regression, postoperative sleep quality (OR, 0.70; 95% CI, 0.62– 0.79), anxiety level (OR, 0.77; 95% CI, 0.62– 0.95) and recovery time in post-anesthesia care unit (PACU) (OR, 0.69; 95% CI, 0.56– 0.98) were identified as significant predictors associated with patient satisfaction.Conclusion: A subanesthetic dose of esketamine (0.15– 0.3 mg/kg/h) as an adjuvant can improves the sedative and analgesic effects of dexmedetomidine and remifentanil during anesthesia for liposuction surgery.Clinical Trial Registration: ChiCTR2400080363.Keywords: esketamine, sedation, analgesia, satisfaction, liposuction

Ling Duan,1 Wenhui Guo,1 Shuo Yin,1 Shoubo Yang,1 Jie Liu,2 Yunyun Duan,3 Gehong Dong,4 Wenbin Li,1 Feng Chen1 1Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 2Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 3Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 4Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of ChinaCorrespondence: Wenbin Li; Feng Chen, Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, No. 119 West Nansihuan Road, Beijing, 100070, People’s Republic of China, Tel +86-10-59975034, Email liwenbin@ccmu.edu.cn; chenfeng406@sina.comPurpose: To investigate the prognostic significance of pan-immune-inflammation value (PIV) and PILE score (based on PIV, lactate dehydrogenase (LDH), and Eastern Cooperative Oncology Group Performance Status (ECOG PS)) in patients with primary central nervous system lymphoma (PCNSL).Patients and Methods: A total of 109 patients were enrolled. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The PILE score was incorporated based on PIV, LDH levels, and ECOG PS. The Kaplan–Meier curves and Cox hazards regression models were applied for survival analyses. The relationship between PIV, PILE, and therapeutic response was examined.Results: Baseline high PIV was significantly associated with worse overall survival (OS) in univariate (HR 3.990, 95% CI 1.778– 8.954, p < 0.001) and multivariate (HR 3.047, 95% CI 1.175– 7.897, p = 0.022) analyses. High PIV was also associated with worse progression-free survival (PFS) in univariate (HR 2.121, 95% CI 1.075– 4.186, p = 0.030) but not significant in multivariate analyses. PIV outperformed other systemic inflammation parameters. The patients in the high PILE group (PILE score 2– 3) had worse OS (p = 0.008) and PFS (p < 0.001) compared to the low PILE group (PILE score 0– 1). PILE was independently associated with therapeutic response to initial treatment (OR 0.17, 95% CI 0.05– 0.46; p < 0.001).Conclusion: High PIV and PILE were correlated with worse clinical outcomes in PCNSL patients, indicating that PIV and PILE might be a powerful predictor of prognosis and a potential predictive indicator for therapeutic response in PCNSL.Keywords: primary central nervous system lymphoma, pan-immune inflammation value, PILE score, prognosis

Junqi Liao,1,&ast; Yuan Zhu,1,2,&ast; Aimei Zhang,1 Dan Wu,1 Xiaohui Yan,1 Qiuhua He,1 Fantao Song,1 Jingyi Chen,1 Yunze Li,1 Li Li,1 Zhaoyao Chen,1 Wenlei Li,1 Qin Yang,2 Zhuyuan Fang,3 Minghua Wu1 1Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 2Department of Medicine, Physiology and Biophysics, UC Irvine Diabetes Center, University of California Irvine (UCI), Irvine, CA, USA; 3Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minghua Wu, Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, 155 Hanzhong Road, Nanjing, 210029, People’s Republic of China, Email yfy0069@njucm.edu.cn Zhuyuan Fang, Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, 155 Hanzhong Road, Nanjing, 210029, People’s Republic of China, Email fangzhuyuan@njucm.edu.cnBackground: The relationship between insulin resistance-related indices and the outcomes of acute ischemic stroke (AIS) is still unclear. This study aimed to explore the association between the Apo B/Apo A-1 ratio and the Prognostic Nutritional Index (PNI) with the 90-day outcomes of AIS.Methods: A total of 2011 AIS patients with a 3-month follow-up were enrolled in the present study from January 2017 to July 2021. Multivariate logistic regression modeling was performed to analyze the relationship between Apo B/Apo A-1 ratio, PNI, and AIS poor outcomes. The mediating effect between the three was analyzed using the Bootstrap method with PNI as the mediating variable.Results: Among the 2011 included AIS patients, 20.3% had a poor outcome. Patients were categorized according to quartiles of Apo B/Apo A-1 ratio and PNI. Multivariate logistic regression revealed that the fourth Apo B/Apo A-1 ratio quartile had poorer outcomes than the first quartile (OR 1.75,95%CL 1.21– 2.53, P=0.003), and the fourth PNI quartile exhibited a lower risk of poor outcomes than the first quartile (OR 0.40, 95%CL 0.27– 0.61, P< 0.001). PNI displayed a significant partially mediating effect (21.4%) between the Apo B/Apo A-1 ratio and poor AIS outcomes.Conclusion: The Apo B/Apo A-1 ratio is a risk factor for poor AIS outcomes, whereas PNI acts as a protective factor. The association between the ApoB/ApoA-1 ratio and poor AIS outcomes was partially mediated by PNI.Keywords: insulin resistance, Apo B/Apo A-1 ratio, prognostic nutritional index, acute ischemic stroke, outcomes

Fangfang Du,1,&ast; Yujing Dong,2,&ast; Tian Tian,1 Weili Li,1 Feifei Wan,1 Suling Shi3 1Department of Nursing, Henan Vocational College of Tuina, Luoyang City, Henan Province, People’s Republic of China; 2Shool of Nursing,Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, People’s Republic of China; 3Department of Nursing, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang City, Henan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fangfang Du, Department of Nursing, Henan Vocational College of Tuina, No. 10 Xuefu Street, Luolong District, Luoyang City, Henan Province, 471023, People’s Republic of China, Email dufangfang8119@163.comBackground: Stress urinary incontinence (SUI) is effectively managed through pelvic floor muscle training (PFMT), yet poor adherence often undermines its efficacy. Given square dancing’s popularity among middle-aged women, its integration with PFMT could potentially increase patient compliance. This study aims to investigate the impact of a hybrid program combining square dance and PFMT on SUI symptoms, quality of life, and treatment adherence in this demographic.Methods: Seventy-seven female participants from Luoyang were randomly allocated to an intervention group undergoing a 12-week program combining square dancing with PFMT, and two control groups receiving standard health advice or square dancing alone. Outcomes were assessed using subjective urinary incontinence rating, the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), and the Urinary Incontinence Quality of Life Scale (I-QOL), and a PFMT diary for compliance. Satisfaction was scored on a 10-point scale.Results: Participants (mean age: 53.35± 5.11 years) did not differ significantly at baseline. Post-intervention, the intervention group showed significant improvements in SUI symptoms and quality of life compared to both control groups (P < 0.05), with higher compliance (96.54% vs 54.82% in control I) and satisfaction (8.86± 0.85).Conclusion: Combining PFMT with square dancing significantly improved SUI symptoms, quality of life, and adherence among middle-aged women. Notably, despite the COVID-19 pandemic and associated restrictions during the 12-week intervention period, the communal and enjoyable nature of square dancing likely contributed to enhanced motivation and satisfaction. Keywords: stress urinary incontinence, pelvic floor muscle training, compliance, square dance, women, quality of life

Yan Wang,1,2,&ast; Fengmei Li,1,2,&ast; Shanshan Wei,1,2,&ast; Wenqun Li,1,2 Junyong Wu,1,2 Shengnan Li,1,2 Xiongbin Hu,1,2 Tiantian Tang,1,2 Xinyi Liu1,2 1Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Institution of Clinical Pharmacy, Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinyi Liu, Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China, Tel +86-731-8529-2095, Email liuxinyi128@csu.edu.cnPurpose: Mitochondrial damage may lead to uncontrolled oxidative stress and massive apoptosis, and thus plays a pivotal role in the pathological processes of myocardial ischemia-reperfusion (I/R) injury. However, it is difficult for the drugs such as puerarin (PUE) to reach the mitochondrial lesion due to lack of targeting ability, which seriously affects the expected efficacy of drug therapy for myocardial I/R injury.Methods: We prepared triphenylphosphonium (TPP) cations and ischemic myocardium-targeting peptide (IMTP) co-modified puerarin-loaded liposomes (PUE@T/I-L), which effectively deliver the drug to mitochondria and improve the effectiveness of PUE in reducing myocardial I/R injury.Results: In vitro test results showed that PUE@T/I-L had sustained release and excellent hemocompatibility. Fluorescence test results showed that TPP cations and IMTP double-modified liposomes (T/I-L) enhanced the intracellular uptake, escaped lysosomal capture and promoted drug targeting into the mitochondria. Notably, PUE@T/I-L inhibited the opening of the mitochondrial permeability transition pore, reduced intracellular reactive oxygen species (ROS) levels and increased superoxide dismutase (SOD) levels, thereby decreasing the percentage of Hoechst-positive cells and improving the survival of hypoxia-reoxygenated (H/R)-injured H9c2 cells. In a mouse myocardial I/R injury model, PUE@T/I-L showed a significant myocardial protective effect against myocardial I/R injury by protecting mitochondrial integrity, reducing myocardial apoptosis and decreasing infarct size.Conclusion: This drug delivery system exhibited excellent mitochondrial targeting and reduction of myocardial apoptosis, which endowed it with good potential extension value in the precise treatment of myocardial I/R injury.Keywords: mitochondrial targeting, triphenylphosphonium cations, puerarin, ischemic myocardium-targeting peptide, liposomes

Yishan Duan,1,&ast; Jing Ren,2,&ast; Jing Wang,3,&ast; Suyan Wang,4 Rui Zhang,1 Huohuo Zhang,1 Jinrui Hu,1 Wen Deng,1 Weimin Li,1,3,4 Bojiang Chen1,3 1Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China; 2The Integrated Care Management Center, West China Hospital of Sichuan University, Chengdu, Chengdu, Sichuan Province, 610041, People’s Republic of China; 3Precision Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China; 4Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bojiang Chen; Weimin Li, Email cjhcbj@outlook.com; weimin003@163.comPurpose: Early empiric antibiotics were prescribed to numerous patients during the Coronavirus disease 2019 (COVID-19) pandemic. However, the potential impact of empiric antibiotic therapy on the clinical outcomes of patients hospitalized with COVID-19 is yet unknown.Methods: In this retrospective cohort study, early antibiotics use cohort was defined as control group, which was compared with no antibiotic use and delayed antibiotic use cohorts for all-cause mortality during hospitalization. The 1:2 propensity score matched patient populations were further developed to adjust confounding factors. Survival curves were compared between different cohorts using a Log rank test to assess the early antibiotic effectiveness.Results: We included a total of 1472 COVID-19 hospitalized patients, of whom 87.4% (1287 patients) received early antibiotic prescriptions. In propensity-score-matched datasets, our analysis comprised 139 patients with non-antibiotic use (with 278 matched controls) and 27 patients with deferred-antibiotic use (with 54 matched controls). Patients with older ages, multiple comorbidities, severe and critical COVID-19 subtypes, higher serum infection indicators, and inflammatory indicators at admission were more likely to receive early antibiotic prescriptions. After adjusting confounding factors likely to influence the prognosis, there is no significant difference in all-cause mortality (HR=1.000(0.246– 4.060), p = 1.000) and ICU admission (HR=0.436(0.093– 2.04), p = 0.293), need for mechanical ventilation (HR=0.723(0.296– 1.763), p = 0.476) and tracheal intubation (HR=1.338(0.221– 8.103), p = 0.751) were observed between early antibiotics use cohort and non-antibiotic use cohort.Conclusion: Early antibiotics were frequently prescribed to patients in more severe disease condition at admission. However, early antibiotic treatment failed to demonstrate better clinical outcomes in hospitalized patients with COVID-19 in the propensity-score-matched cohorts.Keywords: Coronavirus disease 2019, COVID-19, early antibiotics use, bacterial co-infections, clinical outcomes

Jingyao Liang,1,2,&ast; Wei Li,1,2,&ast; Wenyan Liu,1,2 Yihui Yu,1,2 Hui Ye,1,2 Xibao Zhang1,2 1Institute of Dermatology, Guangzhou Medical University, Guangzhou, Guangdong, 510095, People’s Republic of China; 2Department of Dermatology, Guangzhou Dermatology Hospital, Guangzhou, Guangdong, 510095, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xibao Zhang, Department of Dermatology, Guangzhou Dermatology Hospital, 56 Hengfu Road, Guangzhou, Guangdong, 510095, People’s Republic of China, Tel +8620-83593476, Email gzpfbfzs@163.comAbstract: Prurigo nodularis (PN) is a debilitating chronic neuroimmunologic skin condition due to the intense pruritus and difficult to treat. The pruritogenic cytokines, particularly IL-4, IL-13, IL-22, IL-31, and oncostatin M (OSM), play a crucial role in the pathogenesis of PN, potentially involving the JAK1-STAT pathway. An oral JAK1 inhibitor, abrocitinib, is presently undergoing Phase 2 trials for the treatment of PN. We evaluated the efficacy of abrocitinib at a daily dosage of 100 mg in treating two patients with PN affecting both lower limbs: a 50-year-old male with a 16-year disease history and a 38-year-old female with over three years of disease history, both of whom had failed to respond to multiple conventional treatments. Both patients responded rapidly after one week of treatment and exhibited a marked improvement. Following eight weeks of therapy, near-complete resolution of both pruritus and lesions was achieved, and no adverse effects were reported. Additionally, there were no reported side effects during the initial four months of continued treatment. Abrocitinib is an effective targeted therapy for PN, offering a promising new option for refractory patients.Keywords: prurigo nodularis, abrocitinib, pruritus

Tao Chen,1– 3,&ast; Yumeng Wei,1– 3,&ast; Suyu Yin,1– 3,&ast; Wen Li,1– 3 Yuxiang Wang,1– 3 Chao Pi,1– 3 Mingtang Zeng,3,4 Xiaodong Wang,5 Ligang Chen,6 Furong Liu,7 Shaozhi Fu,8 Ling Zhao2,3 1Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy, Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University; Luzhou, Sichuan, 646000, People’s Republic of China; 3Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 4Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 5Department of Hepatobiliary Diseases, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 6Department of neurosurgery, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 7Department of Oncology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 8Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaozhi Fu, Department of Oncology, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel +86 830-3165698, Fax +86 830-3165690, Email shaozhifu513@163.com Ling Zhao, Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, Sichuan, 646000, China, Tel +86 830 2681630, Email zhaoling@swmu.edu.cnPurpose: The present study aimed to develop a lipid nanoplatform, denoted as “BAL-PTX-LN”, co-loaded with chiral baicalin derivatives (BAL) and paclitaxel (PTX) to promote the anti-lung cancer efficacy of paclitaxel and reduce the toxicity of chemotherapeutic drugs.Methods: BAL-PTX-LN was optimized through central composite design based on a single-factor experiments. BAL-PTX-LN was evaluated by TEM, particle size, encapsulation efficiency, hemolysis rate, release kinetics and stability. And was evaluated by pharmacokinetics and the antitumor efficacy studied both in vitro and in vivo. The in vivo safety profile of the formulation was assessed using hematoxylin and eosin (HE) staining.Results: BAL-PTX-LN exhibited spherical morphology with a particle size of 134.36 ± 3.18 nm, PDI of 0.24 ± 0.02, and with an encapsulation efficiency exceeding 90%, BAL-PTX-LN remained stable after 180 days storage. In vitro release studies revealed a zero-order kinetic model of PTX from the liposomal formulation. No hemolysis was observed in the preparation group. Pharmacokinetic analysis of PTX in the BAL-PTX-LN group revealed an approximately three-fold higher bioavailability and twice longer t1/2 compared to the bulk drug group. Furthermore, the IC50 of BAL-PTX-LN decreased by 2.35 times (13.48 μg/mL vs 31.722 μg/mL) and the apoptosis rate increased by 1.82 times (29.38% vs 16.13%) at 24 h compared to the PTX group. In tumor-bearing nude mice, the BAL-PTX-LN formulation exhibited a two-fold higher tumor inhibition rate compared to the PTX group (62.83% vs 29.95%), accompanied by a ten-fold decrease in Ki67 expression (4.26% vs 45.88%). Interestingly, HE staining revealed no pathological changes in tissues from the BAL-PTX-LN group, whereas tissues from the PTX group exhibited pathological changes and tumor cell infiltration.Conclusion: BAL-PTX-LN improves the therapeutic effect of poorly soluble chemotherapeutic drugs on lung cancer, which is anticipated to emerge as a viable therapeutic agent for lung cancer in clinical applications. Keywords: baicalin derivative, paclitaxel, chemotherapy, lung cancer, lipid nano platform, combination therapy

Weimin Xu,1 Xinyu Wang,2 Lei Yang,2 Muzi Meng,3,4 Chenyu Sun,1 Wanwan Li,1 Jia Li,1 Lu Zheng,1 Tong Tang,1 WenJun Jia,1 Xiao Chen1 1Department of Thyroid and Breast Surgery, The Affiliated Second Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2School of Second Clinical Medicine, AnHui Medical University, Hefei, People’s Republic of China; 3School of Medicine, American University of the Caribbean, Sint Maarten, Kingdom of the Netherlands; 4General Surgery, BronxCare Health System, New York, NY, USACorrespondence: WenJun Jia; Xiao Chen, Email jiawenjun@smail.nju.edu.cn; chenxiao950616@Gmai.comBackground: The Chinese Society of Clinical Oncology Artificial Intelligence System (CSCO AI) serves as a clinical decision support system developed utilizing Chinese breast cancer data. Our study delved into the congruence between breast cancer treatment recommendations provided by CSCO AI and their practical application in clinical settings.Methods: A retrospective analysis encompassed 537 breast cancer patients treated at the Second Affiliated Hospital of Anhui Medical University between January 2017 and December 2022. Proficient senior oncology researchers manually input patient data into the CSCO AI system. “Consistent” and “Inconsistent” treatment categories were defined by aligning our treatment protocols with the classification system in the CSCO AI recommendations. Cases that initially showed inconsistency underwent a second evaluation by the Multi-Disciplinary Treatment (MDT) team at the hospital. Concordance was achieved when MDTs’ treatment suggestions were in the ‘Consistent’ categories.Results: An impressive 80.4% concurrence was observed between actual treatment protocols and CSCO AI recommendations across all breast cancer patients. Notably, the alignment was markedly higher for stage I (85.02%) and stage III (88.46%) patients in contrast to stage II patients (76.06%, P=0.023). Moreover, there was a significant concordance between invasive ductal carcinoma and lobular carcinoma (88.46%). Interestingly, triple-negative breast cancer (TNBC) exhibited a high concordance rate (87.50%) compared to other molecular subtypes. When contrasting MDT-recommended treatments with CSCO AI decisions, an overall 92.4% agreement was established. Furthermore, a logistic multivariate analysis highlighted the statistical significance of age, menstrual status, tumor type, molecular subtype, tumor size, and TNM stage in influencing consistency.Conclusion: In the realm of breast cancer treatment, the alignment between recommendations offered by CSCO AI and those from MDT is predominant. CSCO AI can be a useful tool for breast cancer treatment decisions.Keywords: Chinese Society of clinical oncology artificial intelligence system, CSCO AI, breast cancer, multi-disciplinary treatment, MDT, consistency

Rui Shen,1,2,&ast; Kebin Cheng,3,&ast; Guanyi Li,1 Zhendong Pan,4 Xijier Qiaolongbatu,1 Yuting Wang,1 Cui Ma,1 Xucong Huang,1 Li Wang,1 Wenjing Li,1 Yuanyuan Wang,2 Lili Jing,1 Guorong Fan,2 Zhenghua Wu2 1School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China; 2Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, People’s Republic of China; 4Department of Clinical Pharmacy, Eye and ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenghua Wu, Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 85 Wujin Road, Shanghai, 200080, People’s Republic of China, Tel +86-159-0161-7923, Email wuzhenghua@sjtu.edu.cnPurpose: Alisma orientale (AO, Alisma orientale (Sam). Juzep) has been widely employed for the treatment of macular edema (ME) in traditional Chinese medicine due to its renowned water-relief properties. Nonetheless, the comprehensive investigation of AO in alleviating ME remained unexplored. This study aims to identify the active components of AO that target the eye and investigate its pharmacological effects and mechanisms on ME.Methods: The study commenced with UPLC-Triple-TOF/MS analysis to identify the primary constituents of AO. Zebrafish eye tissues were then analyzed after a five-day administration of AO to detect absorbed components and metabolites. Subsequently, network pharmacology, molecular docking, and molecular dynamics simulations were employed to predict the mechanisms of ME treatment via biological target pathways. In vivo experiments were conducted to corroborate the pharmacological actions and mechanisms.Results: A total of 7 compounds, consisting of 2 prototype ingredients and 5 metabolites (including isomers), were found to traverse the blood-eye barrier and localized within eye tissues. Network pharmacology results showed that AO played a role in the treatment of ME mainly by regulating the pathway network of PI3K-AKT and MAPK with TNF-α centered. Computational analyses suggested that 11-dehydro-16-oxo-24-deoxy-alisol A, a metabolite of alisol A, mitigates edema through TNF-α inhibition. Furthermore, zebrafish fundus confocal experiments and HE staining of eyes confirmed the attenuating effects of alisol A on fundus angiogenesis and ocular edema, representing the first report of AO’s ME-inhibitory effects.Conclusion: In this study, computational analyses with experimental validation were used to understand the biological activity and mechanism of alisol A in the treatment of ME. The findings shed light on the bioactive constituents and pharmacological actions of AO, offering valuable insights and a theoretical foundation for its clinical application in managing ME. Keywords: Alisma orientale, macular edema, network pharmacology, zebrafish, TNF-&#x03B1

Yuan Huang,1,&ast; Hong Yang,2,&ast; Rui Ding,1,&ast; Li Wang,3 Ji Li,2 Wenbo Li,4 Xuzhen Qin,1 Yingchun Xu,1 Jiaming Qian2 1Department of Laboratory Medicine, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Gastroenterology, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Epidemiology and Health Statistics, Institute of Basic Medicine, Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Ultrasound, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuzhen Qin; Jiaming Qian, Email qxz_01@163.com; qianjiaming1957@126.comObjective: Serum pepsinogen (PG) is a good indicator of atrophic changes in the gastric mucosa. Gastric mucosal atrophy is a high-risk factor for gastric cancer. Serological testing for PG combined with endoscopy can help to improve gastric cancer screening. In this study, we established the reference ranges of serum PG-I, PG-II, and the PG-I/II ratio (PGR) in the Chinese population by chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA). Besides, in the real world, doctors are often confused by the results of different testing platforms. Thus, a comparison of methods CLIA and ELISA was performed.Methods: 2904 individuals were enrolled from six regions in China as part of the Chinese Adult Digestive Diseases Surveillance (2016) program. The individuals completed questionnaires and volunteered to undergo examinations, including gastroscopy, urea breath test, abdominal ultrasound examination and routine serologic tests. Serum was collected to measure PGs (including PG-I, PG-II and PGR) by CLIA and ELISA. Participants who were found obvious abnormalities or absent from the examinations were excluded. Ultimately, 747 healthy individuals were enrolled in this study. The Kolmogorov–Smirnov test was used to assess the distribution of variables. The Kruskal–Wallis H or Mann–Whitney U-tests were used to compare different sex, age, and geographical groups. The 95% reference ranges of PGs obtained by the two methods were established according to document CLSI-EP28-A3, with covariates of sex, age, and region. Spearman correlation analysis, linear regression analysis and allowable total error (ATE) zone analysis were utilized for comparing the two methods.Results: On overall, the 95% reference ranges of PG-I, PG-II, and PGR measured by CLIA were 23.00– 110.64 ng/mL, 2.50– 19.13 ng/mL, and 3.87– 13.30, respectively. Meanwhile, the reference ranges of PG-I, PG-II, and PGR measured by ELISA were 36.93– 205.06 ng/mL, 1.65– 17.96 ng/mL, and 7.50– 33.60, respectively. Both PG-I and PG-II levels measured by the two platforms were found to be influenced by sex and age. PGR measured by CLIA was influenced by age but not by sex, while PGR measured by ELISA was not affected by either age or sex. Regional factors did not significantly impact the PG results, except for PG-I detected by ELISA. Ultimately, reference ranges for PGs were established based on age and sex stratification. Additionally, the Spearman correlation analysis revealed that the correlation coefficients for PG-I, PG-II, and PGR detected by the two methods were 0.899, 0.887, and 0.777, respectively, indicating a strong correlation between the two methods. The regression equation for the PG levels detected by two methods was obtained through linear regression analysis. The ATE analysis provided a visual depiction of the consistency between the two methods, clearly indicating the poor agreement between them.Conclusion: This study established the reference ranges of PGs by strict and intact enrollment standard. In addition, the results indicated a strong linear relationship between the two methods, yet with a clear bias, which was valuable for laboratory interpretation.Keywords: pepsinogen, reference range, gastric cancer

Yanan Li,1,2,&ast; Jingyi Hu,1,2,&ast; Ryan Au,1– 3 Cheng Cheng,1,2 Feng Xu,1,2 Weiyang Li,1,2 Yuguang Wu,1,2 Yuan Cui,1,2 Lei Zhu,1,2 Hong Shen1,2 1Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 2Jiangsu Provincial Hospital of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 3Academy of Chinese Culture and Health Sciences, Oakland, CA, 94612, USA&ast;These authors contributed equally to this workCorrespondence: Hong Shen; Lei Zhu, Jiangsu Provincial Hospital of Chinese Medicine (Affiliated Hospital of Nanjing University of Chinese Medicine), 155 Hanzhong Road, Qinhuai District, Nanjing, Jiangsu Province, People’s Republic of China, Tel\Fax +86-025- 86617141, Email shenhong999@njucm.edu.cn; zhulei5100@njucm.edu.cnBackground: Qingchang Tongluo Decoction (QTF) is clinically used for the treatment of intestinal fibrosis in Crohn’s Disease (CD). However, the role of QTF in CD-associated fibrosis and its potential pharmacological mechanism remains unclear.Purpose: The objective of this study was to elucidate the potential mechanism of QTF in treating CD-associated fibrosis, employing a combination of bioinformatics approaches — encompassing network pharmacology and molecular docking — complemented by experimental validation.Methods: To investigate the material basis and potential protective mechanism of QTF, a network pharmacology analysis was conducted. The core components and targets of QTF underwent molecular docking analysis to corroborate the findings obtained from network pharmacology. In vitro, a colon fibrotic model was established by stimulating IEC-6 cells with 10 ng/mL of transforming growth factor(TGF-β 1). In vivo, an intestinal fibrosis model was induced in BALB/c mice by TNBS. The role of QTF in inhibiting the TGF-β 1/Smad signaling pathway was investigated through RT-qPCR, Western blotting, immunohistochemistry staining, and immunofluorescence staining.Results: Network pharmacology analysis revealed that QTF could exert its protective effect. Bioinformatics analysis suggested that Flavone and Isoflavone might be the key components of the study. Additionally, AKT1, IL-6, TNF, and VEGFA were identified as potential therapeutic targets. Furthermore, experimental validation and molecular docking were employed to corroborate the results obtained from network pharmacology. RT-qPCR, Immunofluorescence, and Western blotting results demonstrated that QTF significantly improved colon function and inhibited pathological intestinal fibrosis in vivo and in vitro.Conclusion: Through the application of network pharmacology, molecular docking, and experimental validation, QTF could be confirmed to inhibit the proliferation of intestinal fibroblasts associated with CD and reduce the expression of Collagen I and VEGFA. This effect is achieved through the attenuation of ECM accumulation, primarily via the inhibition of the TGF-β 1/Smad signaling pathway. Keywords: Qingchang Tongluo Decoction, Crohn’s Disease, intestinal fibrosis, network pharmacology, Pharmacology

Ente Li,1,2,&ast; Qingfeng Zhu,3,&ast; Ziman Lv,1,2,&ast; Songsong Xie,3 Chunju Zhang,4 Wei Li,5 Ligu Mi,1,2 Quan Liu,6 Yuanzhi Wang,1,2 Xiaobo Lu2 1Department of Basic Medicine, School of Medicine, Shihezi University, Shihezi City, Xinjiang Uygur Autonomous Region, 832002, People’s Republic of China; 2Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, the Xinjiang Production and Construction Corps, Shihezi University, Shihezi City, Xinjiang Uygur Autonomous Region, 832002, People’s Republic of China; 3The First Affiliated Hospital of Shihezi University Medical College, Shihezi City, Xinjiang Uygur Autonomous Region, 832002, People’s Republic of China; 4Tumxuk Center for Disease Prevention and Control, Tumxuk City, Xinjiang Uygur Autonomous Region, 843806, People’s Republic of China; 5Department of Basic Medicine, School of Medicine, Tarim University, Alaer City, Xinjiang Uygur Autonomous Region, 843300, People’s Republic of China; 6Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, Key Laboratory of Zoonotic Diseases, The First Hospital of Jilin University, Changchun City, Jilin Province, 30061, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanzhi Wang; Xiaobo Lu, Email wangyuanzhi621@126.com; xjykdluxiaobo@126.comAbstract: Visceral leishmaniasis (VL), also known as kala-azar. It is characterized by prolonged intermittent fever, anemia, splenomegaly, hepatomegaly, and skin darkening. VL is primarily endemic in regions, such as Brazil, East Africa, and India. However, Northern Xinjiang, which is located in northwestern China, is considered a low-incidence area for VL, contributing to its status as a neglected infectious disease. In this report, we present a case of VL caused by Leishmania donovani that was diagnosed using metagenomic next-generation sequencing (mNGS). This case underscores the diagnostic value of mNGS, particularly in regions with low incidence of VL. Keywords: Visceral leishmaniasis, Leishmania donovani, metagenomic next-generation sequencing, northwestern China

Weixin Bei,1,2,&ast; Shuhui Dong,1,2,&ast; Guoying Liu,1,3,4,&ast; Lanfeng Lin,2,5,&ast; Yaofei Jiang,1,2 Nian Lu,1,2 Wangzhong Li,1,2 Hu Liang,1,2 Yanqun Xiang,1,2 Weixiong Xia1,2 1Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 4Department of Radiation Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 5Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanqun Xiang; Weixiong Xia, Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People’s Republic of China, Tel +86-20-87343643, Fax +86-20-87343392, Email xiangyq@sysucc.org.cn; xiawx@sysucc.org.cnBackground: We aim to evaluate the efficacy and safety of anti-PD1 rechallenge in combination with chemotherapy in patients with metastatic nasopharyngeal carcinoma (mNPC) who have progressed on prior anti-PD1 therapy.Patients and Methods: We enrolled patients with mNPC who received chemotherapy combined with PD-1 immune-checkpoint inhibitors (ICIs) or chemotherapy alone after prior progression of anti-PD1 therapy. The primary endpoint was progress-free survival (PFS), and the secondary endpoints included overall survival (OS), disease control rate (DCR) and objective response rate (ORR).Results: A total of 96 patients were eligible between January 2015 and December 2020. Thirty-seven (38.5%) were in the PD-1 ICIs re-challenge group, while the remaining 59 patients (61.5%) were in the chemotherapy group. The ORR and DCR of PD-1 ICIs group and chemotherapy group were 37.8% vs 23.7% and 86.5% vs.74.5%, respectively. After a median follow-up period of 21.1 months (IQR 16.1– 28.7), the log-rank analysis demonstrated a significantly improved PFS in the PD-1 ICIs re-challenge group compared to the chemotherapy group (8.4 months [95% CI 4.3– 14.0] vs 5.0 months [95% CI 2.8– 7.2], P = 0.03). However, no significant difference in OS was observed between the two groups (28.3 vs 24.1 months, P = 0.09). The two groups had similar adverse reactions, but the incidence of grade 3 or 4 thrombocytopenia was significantly higher in the PD-1 ICIs re-challenge group (18.9% vs 3.4%, P = 0.025).Conclusion: mNPC patients who progressed from prior anti-PD1 therapy could benefit from the anti-PD1 rechallenge in combination with chemotherapy. However, further validation is needed.Keywords: metastatic nasopharyngeal carcinoma, chemotherapy, PD-1 immune checkpoint inhibitors, second-line treatment strategies

Xiaorong Qin, Hongyan Li, Jianqiu Wu, Weiyan Tang, Wenjuan Li, Kejin Li Department of Internal Medicine, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210009, People’s Republic of ChinaCorrespondence: Hongyan Li, Department of Internal Medicine, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, 42, Baiziting, Xuanwu District, Nanjing, Jiangsu, 210009, People’s Republic of China, Tel/Fax +86-025-83284611, Email drlihongyan12@163.comPurpose: Diffuse large B-cell lymphoma (DLBCL) is a prevalent malignant condition with a dismal prognosis. LncRNA PGM5 antisense RNA 1 (PGM5‐AS1) appears to be intricately involved in the progression of DLBCL, yet the modulatory mechanism remains unclear. The purpose of this study was to explore the expression of lncRNA PGM5-AS1 in DLBCL and its effect on the disease progression of DLBCL, as well as to explore its mechanisms.Patients and Methods: A total of 35 patients were included in the study. The expression levels of PGM5-AS1 and miR-503-5p in DLBCL tumor tissues and cell lines were detected by RT-qPCR. Cell proliferation was assessed using CCK8. Apoptosis rate was determined by flow cytometry. Cell invasion was examined by transwell assays. The specific interaction between PGM5-AS1 and miR-503-5p was verified through dual luciferase reporter gene assays. The immune related factors were detected by ELASA kits. The CD8+ T cells cytotoxicity was evaluated by LDH cytotoxicity kit.Results: In DLBCL tumor tissues and cells, upregulated PGM5-AS1 expression, downregulated miR-503-5p expression, and elevated PD-L1 expression were observed. PGM5-AS1 functioned as a regulator in controlling DLBCL cell proliferation, apoptosis, and invasion by downregulating miR-503-5p expression. When CD8+ T cells were co-cultured with cells transfected with si-PGM5-AS1, the secretion of immunoregulatory factors increased, and the cytotoxicity of CD8+ T cells increased. These effects were mitigated by miR-503-5p inhibitors.Conclusion: PGM5-AS1 accelerated DLBCL development and facilitated tumor immune escape through the miR-503-5p. Our discoveries offered an insight into lncRNA PGM5-AS1 serving as a prospective therapeutic target for DLBCL.Keywords: PGM5-AS1, miR-503-5p, DLBCL, immune escape

Yue Han,&ast; Jingyi Wang,&ast; Jin Zhang,&ast; Xi Zheng, Yijia Jiang, Wei Liu, Wenxiong Li Department of Surgical Intensive Care Unit, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenxiong Li, Department of Surgical Intensive Care Unit, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86 136 0109 7813, Email liwx1126@163.comPurpose: Sepsis-associated acute kidney injury (S-AKI) contributes to high mortality, but it is lack of specific treatments. We aimed to investigate the underlying mechanism of S-AKI and to identify target drugs to alleviate AKI.Methods: We establish a stable mouse model of S-AKI by Pseudomonas aeruginosa incision infection. Based on high-throughput sequencing and bioinformatics analysis, we investigated the underlying mechanism and selected the target drug (VX-702) for S-AKI. An in vitro model established by co-cultured of kidney tubular epithelial cell line (TCMK-1) cells with lipopolysaccharide (LPS)-induced leukemic monocyte/macrophage cells (RAW264.7), we explored the effect of VX-702 on S-AKI.Results: The data showed interleukin (IL)-6 and IL-1β were the hub genes, and the mitogen-activated protein kinase (MAPK) signaling pathway was the main pathway involved in S-AKI. Administration of VX-702 by oral gavage decreased the elevated concentrations of IL-6, IL-1β, serum creatinine, and blood urea nitrogen in mice with S-AKI. Moreover, VX-702 reduced the number of apoptotic cells in damaged kidney tissues. Cell viability was decreased, and the number of apoptotic cells was increased in TCMK-1 cells co-cultured with LPS-induced RAW264.7 cells compared to LPS-induced TCMK-1 cells. VX-702 treatment reversed this effect. VX-702 treatment reduced the levels of phosphorylated p38 MAPK and proinflammatory cytokines in RAW264.7 cells and the supernatant. VX-702 could bind IL-6, IL-1β and MAPK, and affect the binding of IL-1β and its receptor, as demonstrated by molecular docking.Conclusion: VX-702 ameliorated S-AKI by inhibiting the release of proinflammatory cytokines from macrophages, indicating its potential as a novel therapeutic for S-AKI treatment.Keywords: sepsis-associated acute kidney injury, VX-702, macrophages, inflammatory factor, MAPK

Yue Lu,1– 3,&ast; Simin Pan,4,&ast; Wenzhen Li,5 Yao Qi,6,7 Li Li,1– 3 Yu-Hong Yan,1– 3 Jianan Wei,1– 3 Dan-Ni Yao,1– 3 Jingjing Wu,1– 3 Hao Deng,1– 3 Shuyan Ye,1– 3 Haiming Chen,1– 3 Qubo Chen,1– 3 Hengjun Gao,6,7 Ling Han,1– 3 Chuanjian Lu1– 3 1State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, People’s Republic of China; 3Guangdong-Hong Kong-Macau Joint Laboratory on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 5The Clinical College of Acupuncture Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 6Shanghai Molecular Medicine Engineering Technology Research Center, Shanghai, People’s Republic of China; 7Shanghai National Engineering Research Center of Biochip, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Han; Chuanjian Lu, Email linghan99@gzucm.edu.cn; lcj@gzucm.edu.cnBackground: Psoriasis is a widespread chronic, immune-mediated skin disease with frequent recurrences, and is extremely harmful to the physical and mental health of patients, causing enormous suffering and exerting considerable economic burdens on the health care system as a whole. In more than a decade of clinical use, the optimized formula of Yinxieling (PSORI-CM01) has consistently demonstrated its effectiveness for treating psoriasis. However, its underlying mechanism remains largely unexplored.Methods: The network pharmacology analysis was conducted to predict the mechanism and protective effect of PSORI-CM01 in treating psoriasis. Subsequently, we collected blood samples from 21 patients with psoriasis as part of a randomized, double-blind, and double-dummy clinical trial for microRNA expression profiling. Finally, it was experimentally confirmed that PSORI-CM01 improved psoriasis by regulating miR-20a-3p and miR-3184-3p expression.Results: As a result of the network pharmacology analysis, PSORI-CM01 improved psoriasis through the regulation of autophagy, cellular apoptosis, cellular proliferation, and anti-inflammatory processes. In the target-miRNA regulatory network, these key targets were mainly associated with the regulation of hsa-miR-20a-3p, hsa-miR-155-5p, has-miR-3184-3p, hsa-miR-328-3p and hsa-miR-124-3p. Based on the microRNA expression profiling results, the PSORI-CM01 treatment group exhibited five up-regulated genes and 16 down-regulated genes compared with the healthy control group. In particular, miR-20a-3p and miR-3184-3p were the primary differentially expressed microRNAs, and they were significantly enriched in the signaling pathways involving autophagy, apoptosis, proliferation, and anti-inflammation. Further experiments confirmed that PSORI-CM01 effectively regulates miR-20a-3p and miR-3184-3p, resulting in increased autophagy.Conclusion: We demonstrated by combining network pharmacology and clinical studies of miRNA expression profiles in PBMCs that PSORI-CM01 effectively modulated miR-20a-3p and miR-3184-3p, leading to an increase in autophagy and a decrease in keratinocyte proliferation.Keywords: PSORI-CM01, Psoriasis vulgaris, MicroRNA expression profile, network pharmacology, autophagy

Jiejie Guo,1– 3 Yanzi Cao,1 Ting Zhang,2 Chunshuang Xu,1 Zhitao Liu,1,4 Wanyi Li,1 Qinwen Wang1 1Zhejiang Key Laboratory of Pathophysiology, NBU Health Science Center, Ningbo University, Ningbo, People’s Republic of China; 2Department of Clinical Laboratory, The First People’s Hospital of Wenling, Taizhou, People’s Republic of China; 3Department of Neurology, The First People’s Hospital of Wenling, Taizhou, People’s Republic of China; 4Fujian Normal University, Fuzhou, People’s Republic of ChinaCorrespondence: Qinwen Wang, Zhejiang Key Laboratory of Pathophysiology, NBU Health Science Center Ningbo University, Ningbo, People’s Republic of China, Email wangqinwen@nbu.edu.cnBackground: There is growing interest in the role of physical activity in patients with of Alzheimer’s disease (AD), particularly regarding its impact of cognitive function, gut microbiota, metabolites, and neurotrophic factors.Objective: To investigate the impact of multisensory fusion training (MSFT) combined with 7, 8-dihydroxyflavone (DHF) on the behavioral characteristics, protein expression, microbiome, and serum metabolome using the AD model in mice induced with amyloid-β (Aβ).Methods: We assessed cognitive ability, anxiety-like and depression-like behaviors in Aβ mice using behavioral measures. Western blotting was employed to detect the expression of relevant proteins. The 16S rRNA gene sequencing and metabolomics were used to analyze changes in the intestinal microbial composition and serum metabolic profile, respectively, of Aβ mice.Results: The behavioral outcomes indicated that a 4-week intervention combining DHF and MSFT yielded remarkable improvements in cognitive function and reduced anxiety and depression-like behaviors in Aβ mice. In the hippocampus of Aβ mice, the combined intervention increased the levels of BDNF, VGF, PSD-95, Nrf2, p-GSK3β and p-CREB proteins. Analyses of sequence and metabolomic data revealed that Bacteroides and Ruminococcaceae were remarkably more abundant following the combined intervention, influencing the expression of specific metabolites directly linked to the maintenance of neuronal and neurobehavioral functions. These metabolites play a crucial role in vital processes, such as amino acid metabolism, lipid metabolism, and neurotransmitter metabolism in mice.Conclusion: Our study highlighted that MSFT combined with DHF improves cognitive impairment, anxiety, and depression-like behavior in Aβ mice through multiple mechanisms, and further validated the correlation between the gut microbiome and serum metabolome. These findings open up a promising avenue for future investigations into potential treatment strategies for AD.Keywords: Alzheimer’s disease, brain-derived neurotrophic factor, cognitive impairment, acousto-optic stimulation, treadmill exercise