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Yong Chen,1 Mang He,1 Si-Jin Zhao,2 Yan-Juan Chen,1 Yong-Qiao Zhang,2 Xiao-Long Chen,2 Chuan-Jie Yang,2 Yu-Zhuo Luo,2 Kutty Selva Nandakumar,3 Zhou-Xiong Xing,4 Mei Tian1 1Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China; 2Undergraduate Students of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China; 3Docent, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; 4Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of ChinaCorrespondence: Mei Tian; Zhou-Xiong Xing, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi City, Guizhou Province, People’s Republic of China, Email 348820517@qq.com; xingzhouxiong111@126.comPurpose: To investigate the clinical value of adding Jin-gu-lian (JGL) capsules into rheumatoid arthritis (RA) treatment by examining its impact on disease activity and quality of life (QoL) through a real-world study (RWS).Patients and methods: RWS was conducted to compare the inflammatory markers, including IgM-RF, ESR, and CRP, between RA patients treated with only Western medicine (reference group) and Western medicine plus JGL (study group) during one-year follow-up. The clinical data was acquired from the hospital information system (HIS). Telephone call-based follow-up on QoL (SF-36) and accompanying symptoms, including gastrointestinal complaints, attacks of pneumonia, herpes zoster, URTIs, UTIs, and LTBIs. Finally, the anti-rheumatic drugs given to both groups were also compared. RWS was further validated for its feasibility by performing studies with hydroxychloroquine (HCQ) treatment, which is a commonly used anti-rheumatic drug for RA with mild effect.Results: The study group failed to show a significant effect on inflammatory markers, especially on the CRP levels, indicating no additional clinical value of supplementing with JGL. Similarly, at the endpoint, no significant differences between the two groups on QoL and related symptoms were observed. Our study suggests that the patients in the study group might need more anti-rheumatic drugs to fill the treatment insufficiency, and the application ratio of NSAIDs would be significantly higher than the reference group. By conducting this study on HCQ treatment, the positive aspects of controlling disease activity and reducing NSAIDs application were found, which demonstrates the utility of performing the RWS to evaluate the effect of JGL.Conclusion: Adding JGL did not significantly improve the clinical efficacy of RA treatment by this RWS. Folk herbal prescriptions such as JGL are suggested to underwent strict clinical trials before application.Keywords: real-world study, rheumatoid arthritis, traditional Chinese medicine, disease activity, hydroxychloroquine

Juan Qiao,1,2 Shiwan Tao,2 Yurong Sun,3,4 Jiabo Shi,2,5 Yu Chen,2,5 Shui Tian,3,4 Zhijian Yao,2,5 Qing Lu3,4 1Department of Psychology, Xuzhou East Hospital Affiliated to Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Psychiatry, Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China; 3School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, People’s Republic of China; 4Key Laboratory of Child Development and Learning Science, Ministry of Education, Nanjing, People’s Republic of China; 5Nanjing Brain Hospital, School of Medicine, Nanjing University, Nanjing, People’s Republic of ChinaCorrespondence: Zhijian Yao, Department of Psychiatry, Brain Hospital Affiliated to Nanjing Medical University, Nanjing, 210029, People’s Republic of China, Email zjyao@njmu.edu.cn Qing Lu, Email luq@seu.edu.cnBackground: γ-aminobutyric acid (GABA) and its main receptor, the GABAA receptor, are implicated in major depressive disorder (MDD). Anxious depression (AD) is deemed to be a primary subtype of MDD. The amygdala and the dorsolateral prefrontal cortex (DLPFC) are key brain regions involved in emotional regulation. These regions contain the most GABAA receptors. Although the GABAergic deficit hypothesis of MDD is generally accepted, few studies have demonstrated how GABAA receptor gene polymorphisms affect the functions of specific brain regions, in particular, the amygdala and the DLPFC.Methods: The sample comprised 83 patients with AD, 70 patients with non-anxious depression (NAD), and 62 healthy controls (HC). All participants underwent genotyping for polymorphisms of GABAA receptor subunit genes, followed by a resting-state fMRI scan. The HAMD-17 was used to evaluate the severity of MDD. ANOVA was performed to obtain the difference in the imaging data, GABAA receptor multi-locus genetic profile scores (MGPS), and HAMD-17 scores among three groups, then the significant differences between AD and NAD groups were identified. Mediating effect analysis was used to explore the role of functional connectivity (FC) between the amygdala and DLPFC in the association between the GABAA receptor gene MGPS and AD clinical features.Results: Compared with the NAD group, the AD group had a higher GABAA receptor MGPS. AD patients exhibited a negative correlation between the MGPS and FC of the right centromedial (CM) subregion, and the right middle frontal gyrus (MFG). A negative correlation was also observed between the MGPS and anxiety/somatic symptoms. More importantly, the right CM and right MFG connectivity mediated the association between the GABAA receptor MGPS and anxiety/somatic symptoms in patients with AD.Conclusion: The decreased FC between the right MFG and right CM subregion mediates the association between GABAA receptor MGPS and AD.Keywords: anxious depression, GABAA receptor, multi-locus genetic profile scores, dorsolateral prefrontal cortex, amygdala subregion

Yuxia He,1,2,* Yuling Mao,1,2,* Yaoming Chen,3,* Ling Tang,1 Haiyu Hou,1 Chenyun Sun,1 Yaqi Shang,1 Na-Na Tan,4 Lei Li1,2 1Department of Obstetrics and Gynecology, Center for Reproductive Medicine; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Key Laboratory for Reproductive Medicine of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 4Department of Health Management; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Li; Na-Na Tan, Email lileigo@foxmail.com; tannana0212@126.comPurpose: This study investigated the incidence and microbial etiology of embryo contamination in assisted reproductive technology (ART), and its influence on embryo development, pregnancy and neonatal outcomes.Methods: A retrospective analysis was conducted on embryo contamination at the Reproductive Centre of the Third Affiliated Hospital of Guangzhou Medical University, between 2018 and 2021.Results: In the period from 2018 to 2021, the average incidence of embryo contamination was 0.12%. Bacterial growth was observed in 39 cases, with a preponderance of Escherichia coli (20, 51.28%), Streptococcus agalactiae (7, 17.95%). The fertilization rate of contaminated embryos was 18.18% (Klebsiella pneumoniae) to 94.79% (S. agalactiae), the cleavage rate was 9.09% (Enterobacter cloacae) to 98.90% (S. agalactiae), and the available embryo rate of Day 3 was 0 (Klebsiella pneumoniae, Enterobacter cloacae) to 63.33% (S. agalactiae). Blastocyst formation rate was 3.23% (Proteus mirabilis) to 64.29% (Streptococcus mitis). E. coli contamination occurred mostly on Day 1, and S. agalactiae on Days 3 and 5. After rinsing and rescuing treatment, six healthy male babies were born.Conclusion: E. coli and S. agalactiae were the most common bacterial embryo contaminants. Most microbial contamination can significantly decrease the fertilization rate. Embryo transfer after rinsing and continuing culture had no negative effect on neonatal outcomes, but there was an increased risk of early abortion due to E. coli contamination.Keywords: in vitro fertilization, microbial contamination, remedial treatment, pregnancy outcome, neonatal outcomes

Suwen Huang,1,* Wei Xie,1,2,* Yufan Gao,1,3,* Yining Jin,1,3 Yilin Chen,1,2 Guoliang Zhou,1,2 Feng Chen,1,2 Qiaoqiao Jin,1,2 Zihao Wu,1,2 Lingsheng Wang,1,2 Chao Chen,4 Yiyun Weng,1 Guangyong Chen5 1Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2The First School of Medicine, School of Information and Engineering, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3The Second School of Medicine, Wenzhou Medical University, Wenzhou, People’s Republic of China; 4Department of Nutriology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 5Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guangyong Chen, Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China, Email gychen@wmu.edu.cn Yiyun Weng, Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China, Email wengyiyun2012@126.comBackground and Purpose: The dynamic systemic inflammation level and stroke-associated infection (SAI) are related to the prognosis of acute ischemic stroke (AIS). We aimed to explore whether the systemic inflammatory response index (SIRI), systemic immune inflammation index (SII), and their dynamic changes possess predictability for SAI and long-term prognosis.Methods: A total of 1804 AIS patients without intravenous thrombolysis in two hospitals were included. We explored the relationship between SIRI, SII, and their dynamic changes and outcomes by constructing clusters. The mediating effects of SAI between prognosis and systemic inflammation were further evaluated.Results: Each SD increase in the concentration of SIRI exhibited a significant correlation with the risk of poor functional outcome, mortality, and functional dependency. Through K-means clustering analysis, patients with dramatically elevated or decreased systemic inflammation levels of SIRI (OR: 2.293, 95% CI: 1.279– 4.109) and SII (OR: 3.165, 95% CI: 1.627– 6.156) within 7 days had a higher risk of functional outcome. Through mediation analysis, SAI mediated the association between systemic inflammation and poor prognosis (SIRI: 33.73%, SII: 16.01%).Conclusion: Dramatically changing dynamics of SIRI and SII were significantly associated with a higher risk of poor prognosis in AIS patients. SAI mediated the association between systemic inflammation and prognosis at 1 year.Keywords: AIS, inflammation, SAI, mediation analysis, clustering analysis

Yan Yang,1,* Feilin Ge,2,* Chen Luo,1 Cai Liao,1 Junyuan Deng,1 Yunhao Yang,1 Yang Chen,1 Xiao Guo,1 Zhaofang Bai,3 Xiaohe Xiao,3 Chenglin Tang1 1College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 2Department of Chinese Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 3Senior Department of Hepatology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohe Xiao, Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China, Email pharmacy302xxh@126.com Chenglin Tang, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, People’s Republic of China, Email tangchenglin@cqmu.edu.cnBackground: Chronic hepatitis B (CHB) remains a global health challenge, necessitating innovative therapeutic strategies. Enhancing the body’s immune response against the hepatitis B virus (HBV) emerges as a fundamental strategy for achieving a functional cure. While acupuncture has shown potential in immune modulation, its specific anti-HBV effects are not well understood. This study evaluates the potential of electroacupuncture (EA) in HBV infection and explores its underlying immunological mechanisms using a mouse model.Methods: HBV-infected mice were established using the high-pressure hydrodynamic method and divided into four groups: normal saline (NS), EA, sham EA (SE), and tenofovir disoproxil fumarate (TF), with n = 6 per group. During treatment, blood was collected every Sunday via the orbital sinus to monitor HBV DNA, HBsAg, and HBeAg levels. Transcriptomics and metabolomics analyses were employed to unearth clues regarding EA’s anti-HBV mechanism. Validation of these mechanisms included splenic T-cell flow analysis, Western blotting, RT-qPCR, immunofluorescence, and ELISA.Results: Serum HBV DNA levels decreased by 1.10, 0.19, and 1.98 log10 IU/mL in the EA, SE, and TF-treated mice, respectively, compared to the NS. Concurrently, the hepatic HBV DNA levels decreased by 1.09, 0.24, and 2.03 log10 IU/mL. EA also demonstrated superior inhibition of HBV antigens, with serum HBeAg levels decreasing by 43.86%, 8.74%, and 8.03%, and serum HBsAg levels decreasing by 28.01%, 0.26%, and 9.39% in the EA, SE, and TF groups, respectively. Further analysis through transcriptomics and metabolomics revealed that EA’s anti-HBV effects primarily hinge on immune modulation, particularly the IFN-γ/JAK/STAT pathway and taurine metabolism. EA also increased the ratio of splenic CD8+ CD69+ and CD8+ IFN-γ+ T-cells while upregulating key proteins in the JAK/STAT pathway and cytokines associated with antiviral immunity.Conclusion: EA manifests inhibitory effects on HBV, particularly in antigen suppression, with its mode of action intricately linked to the regulation of IFN-γ/JAK/STAT.Keywords: hepatitis B virus, electroacupuncture, antiviral activity, immune modulation, IFN-&#x03B3

Beiying Deng,1,2,* Junhai Zhen,3,* Zixuan Xiang,1,2,* Xiangyun Li,1,2 Cheng Tan,1,2 Ying Chen,1 Pengzhan He,1 Jingjing Ma,4 Weiguo Dong1,* 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Key Laboratory of Hubei Province for Digestive System Disease, Wuhan, People’s Republic of China; 3Department of General Practice, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 4Department of Geriatric, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiguo Dong, Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuhan, Hubei Province, 430060, People’s Republic of China, Tel +86 027-88041911, Email dongweiguo@whu.edu.cnBackground: Ulcerative colitis (UC) is a debilitating intestinal disorder that imposes a significant burden on those affected. Fatty acid metabolism plays a pivotal role in regulating immune cell function and maintaining internal homeostasis. This study investigates the biological and clinical significance of fatty acid metabolism within the context of UC.Methods: Gene expression profiles from patients with UC and healthy controls were retrieved, enabling the identification of differentially expressed genes (DEGs) specific to UC. These DEGs were then intersected with genes related to fatty acid metabolism, resulting in the identification of differentially expressed fatty acid metabolism-related genes (FAM-DEGs). Machine learning was employed to pinpoint key feature genes from the FAM-DEGs, which were subsequently used to construct a predictive UC model and to uncover molecular subtypes associated with fatty acid metabolism in UC. An animal model of UC was established using 3% dextran sulfate sodium (DSS) administration. Western blot analysis confirmed the expression levels of genes in intestinal tissues.Results: The machine learning analysis identified three pivotal genes—ACAT1, ACOX2, and HADHB—culminating in a highly predictive nomogram. Consensus cluster analysis further categorized 637 UC samples into two distinct subgroups. The molecular subtypes related to fatty acid metabolism in UC exhibited significant differences in gene expression, biological activities, and enrichment pathways. Immune infiltration analysis highlighted elevated expression of two genes (excluding HADHB) in subtype 1, which corresponded with a marked increase in immune cell infiltration within this subtype. Western blot analysis demonstrated that ACAT1, ACOX2, and HADHB expression levels in the DSS group were significantly reduced, paralleling those observed in the normal group.Conclusion: This study highlights the critical role of specific fatty acid metabolism-related genes in UC, emphasizing their potential as targets for therapeutic intervention and shedding light on the underlying mechanisms of UC progression.Keywords: fatty acid metabolism, ulcerative colitis, machine learning, biomarkers, pharmacology, immune infiltrations

Yangjia Chen,1,&ast; Zhaocheng Zhuang,1,&ast; Zhixiang Rao2 1Department of Preventive Medicine, School of Health, Quanzhou Medical College, Quanzhou, Fujian, 362011, People’s Republic of China; 2School of Humanities and Management, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yangjia Chen, Department of Preventive Medicine, School of Health, Quanzhou Medical College, Quanzhou, Fujian, 362011, People’s Republic of China, Email 2015018@qzmc.edu.cnObjective: Epidemiological investigations have indicated an association between skin microbiota imbalance and psoriasis, however, the causal relationship has not been confirmed through Mendelian randomization (MR). MR employed genetic instrumental variables (IVs) to evaluate the causal relationship between skin microbiota and psoriasis, providing new insights for potential treatments.Methods: Summary statistics for psoriasis and related traits were available from FinnGen R10 and United Kingdom Biobank (UKB) consortium. The genome-wide association studies (GWAS) on skin microbiota in three skin microenvironments came from two population-based German cohorts. Several selection processes were used to determine the optimal instrumental variables. Five MR methods were performed and different sensitivity analyses approaches yield robustness evidence under different assumptions.Results: 449 SNPs were employed as IVs for 53 bacterial genera, with F-statistics between 20.18 and 42.44, indicating no evidence of weak instrument bias. Bacteroides was associated with psoriasis from UKB in IVW (OR, 95% CI: 0.914, 0.869– 0.961; P < 0.001, PB-H = 0.007). The taxon was also associated with psoriasis vulgaris (IVW: OR, 95% CI, 0.918, 0.872– 0.967; P = 0.001, PB-H = 0.054) and psoriasis and related disorders (IVW: OR, 95% CI, 0.915, 0.875– 0.957; P < 0.001, PB-H = 0.008). Consistent causal estimates were identified in terms of both magnitude and direction, indicating a protective effect of Bacteroides.Conclusion: The MR study found that Bacteroides in the antecubital fossa may protect against psoriasis, offering genetic proof that skin microbiota helps prevent the condition.Keywords: skin microbiota, psoriasis, Mendelian randomization, genus Bacteroides, autoimmune disease, AD

Dan Yao,1 Jiefeng Jiang,1 Qianyun Zhou,1 Caiyun Feng,1 Jianping Chu,2 Zhiyan Chen,1 Jie Yang,1 Jinying Xia,3 Yujia Chen1 1Department of Endocrinology, Xiangshan Hospital of TCM Medical and Health Group, Xiangshan, Ningbo, People’s Republic of China; 2Department of Endocrinology, Ningbo First Hospital, Ningbo, People’s Republic of China; 3Department of Endocrinology, Ningbo No. 2 Hospital, Ningbo, People’s Republic of ChinaCorrespondence: Jiefeng Jiang, Department of Endocrinology, Xiangshan Hospital of TCM Medical and Health Group, Ningbo, 315799, People’s Republic of China, Tel +86-13606781301,, Email xszyyjjf@126.com Dan Yao, Department of Endocrinology, Xiangshan Hospital of TCM Medical and Health Group, Xiangshan, Ningbo, 315799, People’s Republic of China, Tel +86-13777191528, Email 3299048@qq.comAbstract: In recent years, there have been hundreds of reports on insulin autoimmune syndrome (IAS) globally; however, fewer than a hundred patients have undergone genetic testing. Our objective is to examine the background of IAS and the variations in drugs that trigger it among patients who have been genetically tested, aiming to deepen our understanding of this condition. HLA Analysis of 68 cases showed that DR4 is predominant, especially in individuals of East Asian descent, notably in DRB1 &ast;0406. Methimazole was the primary drug associated with IAS in these populations, while in Caucasian individuals, the emphasis was on DRB1 &ast;0403, with lipoic acid being the common inducer. The key factor determining disease risk is the combination of chromosomal allele variations, with HLA class II allele DR4 positive patients showing a strong association with DQA1 &ast;0301/DQB1 &ast;0302.Keywords: insulin autoimmune syndrome, HLA, methimazole, α-lipoic acid

Zhengwen Feng,1 Hui Li,1 Xiaolei Chen,1 Tiancheng Zhang,2 Yanxiang Chen,3 Shuang Shao,1,&ast; Juan Du1,&ast; 1School of General Practice and Continuing Education, Capital Medical University, Beijing, People’s Republic of China; 2Department of General Practice, Dahongmen Community Health Service Center, Beijing, Fengtai District, People’s Republic of China; 3Department of general practice, Changying Community Health Service Center, Beijing, Chaoyang District, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Du; Shuang Shao, School of General Practice and Continuing Education, Capital Medical University, 10 You’ Anmen Outer West 1 st Street, Beijing, 100069, People’s Republic of China, Email cuckoo@ccmu.edu.cn; shaoshuang@ccmu.edu.cnPurpose: Our study aimed to explore the current status of patient participation in medication safety from the perspectives of general practitioners (GPs), pharmacists, and outpatients in Beijing, China.Patients and Methods: A qualitative study using semi-structured in-depth individual interviews with GPs, pharmacists, and outpatients. Subjects were identified by purposive sampling until code saturation. Semi-structured qualitative interviews were conducted with GPs, pharmacists, and patients from community health service centers in three urban districts of Beijing, China. The interviews were transcribed verbatim and the text was analysed using thematic analysis techniques including familiarising with data, generating initial codes, searching for themes, reviewing themes, defining and naming themes, and producing the report.Results: A total of eight GPs, seven pharmacists, and 18 outpatients were interviewed. Data analysis led to the generation of five key themes: (1) mutual trust between patient and GP, (2) communication with healthcare professionals, (3) acquisition of knowledge about medication safety, (4) implementation of medication self-management at home, and (5) different attitudes toward participation in medication decisions. Patients participated in medication safety in multiple ways. However, insufficient knowledge about medication safety, lack of awareness of the patient’s role in ensuring medication safety, shortage of consultation lengths, and being misled by some information were problems with patient participation in medication safety.Conclusion: This exploratory study contributes to our initial understanding of patient participation in medication safety. There were still many issues and barriers in the process of patient participation. Appropriate policies and measures, such as providing various forms of patient education, ensuring sufficient physician-patient communication, giving full play to the role of pharmacists, and making judicious use of digital health tools should be taken to improve medication safety by fully utilising the role of patients.Plain Language Summary: Medication safety is a significant concern around the world. Patient participation in the medication process is effective in reducing the incidence of medication errors and improving medication safety. However, the role of outpatients with chronic conditions in ensuring medication safety is often neglected. This study aims to explore the perspectives and experiences of GPs, pharmacists, and outpatients by qualitative interviews in Beijing, China. The study involved a series of interviews with eight GPs, seven pharmacists, and 18 outpatients living with noncommunicable diseases. The interview revealed five themes: (1) mutual trust between patient and GP, (2) communication with healthcare professionals, (3) acquisition of knowledge about medication safety, (4) implementation of medication self-management at home, and (5) different attitudes toward participation in medication decisions. The findings might help propose suggestions for patient participation in medication safety. Integrating these findings into future studies can help healthcare professionals formulate interventions and better support patients in participating in the medication process.Keywords: medication safety, patient participation, patient safety, qualitative study, noncommunicable disease, community health service centers

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

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

Ying Chen,1,&ast; Hanyu Liang,2,&ast; Huaibin Jiang3 1School of Arts and Child Education, Yango University, Fuzhou, People’s Republic of China; 2School of Psychology, Inner Mongolia Normal University, Hohhot, People’s Republic of China; 3School of Education, Fujian Polytechnic Normal University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaibin Jiang, School of Education, Fujian Polytechnic Normal University, No. 1 Campus New Village, Longjiang Street, Fuqing, 350300, People’s Republic of China, Email jianghuaibin@126.comPurpose: Non-suicidal self-injury (NSSI) is a growing public health concern among college students, with cybervictimization (CV) emerging as a significant contributing factor. Grounded in the experiential avoidance theory, this study investigates the mediating roles of cognitive fusion and negative emotions in the relationship between CV and NSSI, providing new insights into these key variables.Methods: A convenience sample of 457 undergraduate students (29% male; mean age 18.36± 0.66 years) from two universities in Fujian Province participated in this study. Data were collected using the Cyberbullying Victimization Scale, Cognitive Fusion Questionnaire, Positive and Negative Affect Schedule, and Non-Suicidal Self-Injury Scale. Descriptive statistics and Pearson correlation analysis were conducted using SPSS 25.0, while the mediating effects were analyzed using Process 3.5.Results: (1) Significant positive correlations were found among CV, cognitive fusion, negative emotions, and NSSI (p < 0.01). (2) CV was directly associated with NSSI (β = 0.22, p < 0.001) and positively predicted both cognitive fusion (β = 0.17, p < 0.001) and negative emotions (β = 0.15, p < 0.01). Additionally, cognitive fusion (β = 0.16, p < 0.01) and negative emotions (β = 0.11, p < 0.05) significantly predicted NSSI. (3) Mediation analyses revealed that cognitive fusion and negative emotions mediated the CV-NSSI relationship through three pathways: CV→cognitive fusion→NSSI (mediation effect = 0.026), CV→negative emotions→NSSI (mediation effect = 0.02), and CV→cognitive fusion→negative emotions→NSSI (mediation effect = 0.01).Conclusion: The study confirms that CV influences NSSI indirectly through cognitive fusion and negative emotions, supporting the experiential avoidance model. These findings underscore the importance of addressing cognitive and emotional processes in interventions aimed at reducing NSSI among college students.Keywords: cybervictimization, non-suicidal self-injury, cognitive fusion, negative emotions

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

Lei Wang,1,&ast; Kai Wang,2,&ast; Yuwen Chen,1 Xiaoyu Zhang,1,3 Wenhao Xu,1,3 Zhong Dong,1,3 Yu Wang1,3,4 1Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230000, People’s Republic of China; 2Department of Neurology, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230000, People’s Republic of China; 3Department of Neurology, Anhui Public Health Clinical Center, Hefei, Anhui Province, 230000, People’s Republic of China; 4Department of Neurology, Anqing First People’s Hospital Affiliated to Anhui Medical University, Anqing, Anhui Province, 246000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Wang, Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230000, People’s Republic of China, Email yw4d@hotmail.comObjective: To investigate the effects of inhibiting the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome on neuronal damage and chronic pro-inflammatory responses during epileptogenesis in a mouse model of pilocarpine-induced status epilepticus (SE).Methods: Mice were randomly allocated into three groups: control, SE, and SE + MCC 950. The expression patterns of M1 and M2 microglial biomarkers in the hippocampus were quantified using Western blotting, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunofluorescence staining. Additionally, seizure susceptibility, video-electroencephalography recording, Morris water maze test, and brain immunofluorescence staining were performed to evaluate the epileptic brain 4 weeks post-SE.Results: Within 72 hours post-SE, hippocampal microglia demonstrated a preferential polarization towards the M1 phenotype, a trend that was mitigated by NLRP3 inflammasome inhibition. During epileptogenesis, SE mice treated with NLRP3 inflammasome inhibition exhibited reduced neuronal damage, improved cognitive function, decreased seizure susceptibility, and attenuated chronic pro-inflammatory responses.Conclusion: Inhibition of NLRP3 inflammasome post-SE effectively ameliorates neuronal loss, seizure susceptibility, and cognitive dysfunction during epileptogenesis. This neuroprotective effect may be mediated through the mitigation of chronic pro-inflammatory responses within the epileptic brain.Keywords: NLRP3 inflammasome, microglial polarization, M1 microglia, epileptogenesis, chronic pro-inflammatory response

Chao Zeng,1,&ast; Lu Li,1,&ast; Mengrui Wang,2,&ast; Jun Xiong,1 Wenjuan Pang,1 Haiyan Yu,1 Jiadi He,1 Xuguang Wang,1 Yingying Chen,1 Yanyan Sun1 1Department of Anesthesiology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China; 2Department of Anesthesiology, Peking University Third Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanyan Sun; Jun Xiong, Department of Anesthesiology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China, Email b2008194@126.com; xiongjun107@hotmail.comObjective: Ciprofol is a novel anesthetic agent, its efficacy and safety had been verified and its clinical implementation has been expanded. However, the knowledge about ciprofol in children is meager. The aim of study is to evaluate the safety and effectiveness of ciprofol in general anesthesia in children undergoing adenoidectomy and adenotonsillectomy, compared with propofol.Materials: We retrospectively analyzed data of children who underwent adenoidectomy or adenotonsillectomy with general anesthesia from June to August 2023 to evaluate the safety and effectiveness of ciprofol. The primary outcomes included hemodynamic changes during induction and postoperative complications in post-anesthesia care unit. The secondary outcomes were extubation time, pediatric anesthesia emergence delirium (PAED) score. Meanwhile, subgroup analysis was performed based on age.Results: 301 children met the inclusion criteria, 157 received ciprofol induction and 144 received propofol. Patient demographics and operation-related information were similar in the two groups. However, the dosage of dexmedetomidine in the propofol group was significantly higher than that of the ciprofol group (p=0.001). The trends of hemodynamic shift during induction and intubation were the same in the two groups. The PAED scores on post-extubation 10min and 20min were significantly reduced in the ciprofol group (p< 0.001 and p=0.046). Moreover, in the ≤ 72 months and the > 72 months subgroups, the scores were also significantly lower in the ciprofol group on post-extubation 10min. With the score of > 10, the incidence of emergence delirium of the ciprofol group was significantly lower on post-extubation 10min and 20min in the population and the ≤ 72 months subgroups (p=0.03 and p=0.02). There were no obvious postoperative complications in both groups.Conclusion: Ciprofol exhibited advantageous characteristics in the induction of children, such as stable hemodynamics, a relatively lower incidence of postoperative delirium without apparent post-anesthesia complications. Ciprofol may emerge as a novel option for general anesthesia in pediatric patients.Keywords: ciprofol, propofol, adenoidectomy, child, general anesthesia, delirium

Min He, Huinan Wu, Guanrong Lin, Yongqin Wang, Longling Shi, Chaoling Huang, Qingyun Xu, Zhenxing Li, Shanbo Huang, Yanni Chen, Na Li Department of Endocrinology, Shishi General Hospital, Shishi, Fujian, 362700, People’s Republic of ChinaCorrespondence: Min He, Department of Endocrinology, Shishi General Hospital, No. 2156 Shijin Road, Shishi, Fujian, 362700, People’s Republic of China, Tel +8613506048712, Email heminhem463@163.comObjective: This study proposes a region-wide blood glucose management system to solve the problem of blood glucose management in patients with diabetes.Methods: A professional team of doctors, nurses and dietitians jointly developed a region-wide blood glucose management system. The system operates through a collaborative approach where each team member utilises their specialised role, such as data monitoring, algorithm development or patient support, to contribute to a comprehensive blood glucose management network. This integration ensures accurate glucose tracking, personalised feedback and timely adjustments to treatment plans. The system allows the patient to have a good treatment plan, giving comprehensive medical guidance, and the physician team is responsible for the patient’s health status.Results: The region-wide blood glucose management system increased the overall blood glucose monitoring rate of patients and reduced the hospitalisation time (from 11.27 days to 9.52 days) and hospitalisation costs (from 12,173.8 yuan to 9502.4 yuan). At the same time, the system effectively counted the incidence and occurrence time of hyperglycaemia and hypoglycaemia adverse events, which can provide a reference for clinical prevention of adverse events.Conclusion: A region-wide blood glucose management system can improve medical efficiency, save medical resources and provide a strong guarantee for the health of patients with diabetes. Compared with the traditional diabetes management mode, the region-wide blood glucose management system is more systematic and standardised, meaning it can better meet the needs of patients with diabetes.Keywords: diabetic, glucose management, professional team, guarantee for the health, improve medical efficiency

Jingying Xu, Yuan Chen, Jianhua Yu, Shourong Liu, Ying Meng, Chaodan Li, Qian Huang, Yunlei Xiao Department of Infectious Diseases, Hangzhou Xixi Hospital, Hangzhou Sixth People’s Hospital, Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Qian Huang; Yunlei Xiao, Department of Infectious Diseases, Hangzhou Xixi Hospital, Hangzhou Sixth People’s Hospital, Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, No. 2, Hengbu Street, Liu Xia Town, Xihu District, Hangzhou, 310023, Zhejiang, People’s Republic of China, Tel +8613575746522 ; +8615258639960, Email tcm99hq@163.com; 15258639960@163.comPurpose: Developing countries, invasive Salmonella infections can cause considerable morbidity and mortality. There is a relative lack of data on coinfection with Salmonella in HIV-infected patients in Hangzhou, China.Patients and Methods: In this study, we manually collected case data of patients aged > 18 years with HIV combined with invasive Salmonella infections admitted to Xixi Hospital in Hangzhou from January 2012 to August 2023 by logging into the Hospital Information System, and identified 26 strains of invasive Salmonella using a fully automated microbiological identification system and mass spectrometer. Serotypes were determined using Salmonella diagnostic sera based on the White-Kauffmann-Le Minor scheme. Drug sensitivity tests were performed using the automated instrumental method of the MIC method.Results: A total of 26 HIV-infected patients with invasive Salmonella coinfections were identified over 11 years; Twenty-five of the 26 patients (96.2%) were males, with a mean age of 33.5 years (26.75, 46.75). The most common type of infection was bloodstream infection (92.3%). One patient also had concomitant meningitis and osteoarthritis, followed by pneumonia (7.7%). The presence of multiple bacterial infections or even multiple opportunistic pathogens was clearly established in 7 (26.9%) patients. Three (11.6%) patients were automatically discharged from the hospital with deterioration of their condition, and one (3.8%) patient died. Salmonella enteritidis was the most common serotype in 6 patients (23.2%), and Salmonella Dublin was the most common serotype in 6 patients (23.2%). Drug sensitivity results revealed multidrug resistance in a total of 8 (30.8%) patients.Conclusion: The clinical presentation of invasive Salmonella infection in HIV patients is nonspecific and easily masked by other mixed infections. A CD4+ count < 100 cells/μL and comorbid intestinal lesions may be important susceptibility factors. Salmonella has a high rate of resistance to common antibiotics, and the risk of multidrug resistance should not be ignored.Keywords: Salmonella, invasiveness, HIV, serotype, antibiotic resistance

Fuming Li,1,2 Shimeng Liu,1,2 Yuanyuan Gu,3 Shunping Li,4 Ying Tao,1,2 Yan Wei,1,2 Yingyao Chen1,2 1School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2National Health Commission Key Laboratory of Health Technology Assessment (Fudan University), Shanghai, People’s Republic of China; 3Macquarie University Centre for the Health Economy, Macquarie Business School & Australian Institute of Health Innovation, Macquarie University, Macquarie Park, Macquarie Park, New South Wales, Australia; 4Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Shimeng Liu; Yingyao Chen, School of Public Health, Fudan University, 130 Dongan Road, Xuhui, Shanghai, 200032, People’s Republic of China, Tel +86 198 2182 4471 ; +86 135 6450 8981, Email smliu19@fudan.edu.cn; yychen@shmu.edu.cnPurpose: Discrete choice experiment (DCE) and profile case (case 2) best-worst scaling (BWS) present uncertainties regarding the acceptability of quantifying individual healthcare preferences, which may adversely affect the validity of responses and impede the reflection of true healthcare preferences. This study aimed to assess the acceptability of these two methods from the perspective of patients with type 2 diabetes mellitus (T2DM) and examine their association with specific characteristics of the target population.Patients and Methods: This cross-sectional study was based on a nationally representative survey; data were collected using a multistage stratified cluster-sampling procedure between September 2021 and January 2022. Eligible adults with confirmed T2DM voluntarily participated in this study. Participants completed both the DCE and case 2 BWS (BWS-2) choice tasks in random order and provided self-reported assessments of acceptability, including task completion difficulty, comprehension of task complexity, and response preference. Logistic regression and random forest models were used to identify variables associated with acceptability.Results: In total, 3286 patients with T2DM were included in the study. Respondents indicated there was no statistically significant difference in completion difficulty between the DCE and BWS-2, although the DCE scores were slightly higher (3.07 ± 0.68 vs 3.03 ± 0.67, P = 0.06). However, 1979 (60.2%) respondents found the DCE easier to comprehend. No significant preferences were observed between the two methods (1638 (49.8%) vs 1648 (50.2%)). Sociodemographic factors, such as residence, monthly out-of-pocket costs, and illness duration were significantly associated with comprehension complexity and response preference.Conclusion: This study yielded contrasting results to most of previous studies, suggesting that DCE may be less cognitively demanding and more suitable for patients with T2DM from the perspective of self-reported acceptability of DCE and BWS. This study promotes a focus on patient acceptability in quantifying individual healthcare preferences to inform tailored optimal stated-preference method for a target population.Plain Language Summary: Stated preference methodologies such as the discrete choice experiment (DCE) and case 2 best-worst scaling (BWS-2) are gaining popularity as methods for quantifying individual preferences in healthcare. However, the acceptability of the two methods to participants must be considered in practice to reduce cognitive burden and ensure the validity of preference elicitation.DCE was perceived to be less cognitively burdensome than BWS-2. In contrast to patients who thought that DCE was more acceptable, BWS-2 was more accepted by rural patients, patients who lived with the disease for a longer period, and those who had lower monthly out-of-pocket costs.These findings demonstrate potential differences in the acceptability of DCE and BWS-2 for patients with type 2 diabetes mellitus. To improve efficiency, it would be useful for researchers to consider the optimal stated preference method for identifying target populations according to sociodemographic and disease-related characteristics.Keywords: patient-reported outcomes, acceptability, discrete choice experiment, best-worst scaling, preference, type 2 diabetes

Jie Zhang, Xuelin Yao, Yijing Chen, Qing Feng, Yi Zhang, Tian Jiang, Songtao Tang, Nan Zhang, Fang Dai, Honglin Hu, Qiu Zhang Department of Endocrinology, First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Qiu Zhang; Honglin Hu, Department of Endocrinology, First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Shushan District, 230032, People’s Republic of China, Email zhangqiu@ahmu.edu.cn; huhonglin@ahmu.edu.cnBackground: Diabetes mellitus and hypertension often coexist and share common risk factors. This study investigated the correlation between glycemic management and the prevalence of hypertension among Chinese adults diagnosed with type 2 diabetes mellitus (T2DM).Methods: This study included 1715 patients with T2DM from four cities in Anhui Province, China. Sociodemographic characteristics of the sample participants were collected via questionnaires. A univariate analysis of variance (ANOVA) was utilized for continuous variables, and chi-square testing was used for categorical variables. Binary logistic regression was utilized to examine the relationship between blood pressure and variables including fasting plasma glucose (FPG), glycosylated haemoglobin (HbA1c), body mass index (BMI), waist circumference (WC), physical activity, dyslipidemia, and family history of hypertension.Results: FPG levels did not increase the risk of hypertension, while HbA1c was significantly and negatively associated with hypertension risk. HbA1c levels ranged from 7.2 to 8.6%, with odds ratios (OR) of 0.68 and 95% confidence intervals (CI) of 0.48 to 0.97 and a significant p value of less than 0.05. For the HbA1c levels above 8.6%, the OR was 0.58 with a 95% CI of 0.39 to 0.87 and a significant p value of less than 0.01. Furthermore, advanced age, higher BMI, greater waist circumference, presence of dyslipidemia, and positive family history of hypertension were all found to be significantly and independently linked to a heightened risk of developing hypertension. These associations remain significant after further adjustment.Conclusion: There was a negative association between HbA1c and the risk of hypertension, and the association remained significant after adjustment for antihypertensive drug use.Keywords: FPG, HbA1c, T2DM, hypertension

Cheng-Yu Shentu,1 Hao-Bin Wang,1 Xiao Peng,2 Dong-Chen Xu,1 Li-Na Qian,1 Yong Chen,1,2 Li-Hua Peng1– 3 1College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of China; 2Jinhua Institute of Zhejiang University, Jinhua, Zhejiang, 321299, People’s Republic of China; 3State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, Macau SAR, People’s Republic of ChinaCorrespondence: Li-Hua Peng; Yong Chen, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of China, Email lhpeng@zju.edu.cn; chenyong1@zju.edu.cnAbstract: Osteoarthritis (OA) is a degenerative disease commonly seen in middle-aged and elderly people. Multiple cytokines are involved in the local tissue damage in OA. Currently, non-pharmacologic and surgical interventions are the main conventional approaches for the treatment of OA. In terms of pharmaceutical drug therapy, NSAIDs and acetaminophen are mainly used to treat OA. However, it is prone to various adverse reactions such as digestive tract ulcer, thromboembolism, prosthesis loosening, nerve injury and so on. With the in-depth study of OA, more and more novel topical drug delivery strategies and vehicles have been developed, which can make up for the shortcomings of traditional dosage forms, improve the bioavailability of drugs, and significantly reduce drug side effects. This review summarizes the immunopathogenesis, treatment guidelines, and progress and challenges of topical delivery technologies of OA, with some perspectives on the future pharmacological treatment of OA proposed.Keywords: topical drug delivery, immuno-therapy, cytokines, osteoarthritis

Hao Hong,1,&ast; Suya Zhou,2,&ast; Junyao Zheng,3 Haimin Shi,3 Yue Chen,4 Ming Li3 1Department of Intensive Care Unit, The First Affiliated Hospital of Soochow University, Soochow, Suzhou, People’s Republic of China; 2Laboratory Nephrology, Jinshan hospital of Fudan University, Shanghai, People’s Republic of China; 3Laboratory Nephrology, The First Affiliated Hospital of Soochow University, Soochow, Suzhou, People’s Republic of China; 4Laboratory Nephrology, The First People’s Hospital of Kunshan, Soochow, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ming Li, Email 1925924373@qq.comPurpose: The aim of this study was to investigate the changes of different metabolites in the body fluids of non-dialysis patients with chronic kidney disease (CKD) using a metabolomics approach. The goal was to identify early biomarkers of CKD progression through metabolic pathway analysis.Patients and Methods: Plasma samples from 47 patients with stages 1– 4 CKD not requiring dialysis and 30 healthy controls were analyzed by liquid chromatography-mass spectrometry (LC-MS). Using multivariate data analysis, specifically a partially orthogonal least squares discriminant analysis model (OPLS-DA), we investigated metabolic differences between different stages of CKD. The sensitivity and specificity of the analysis were evaluated using the Area Under Curve (AUC) method. Furthermore, the metabolic pathways were analyzed using the Met PA database.Results: Plasma samples from CKD patients and controls were successfully differentiated using an OPLS-DA model. Initially, twenty-five compounds were identified as potential plasma metabolic markers for distinguishing CKD patients from healthy controls. Among these, six compounds (ADMA, D-Ornithine, Kynurenine, Kynurenic acid, 5-Hydroxyindoleacetic acid, and Gluconic acid) were found to be associated with CKD progression It has been found to be associated with the progression of CKD. Changes in metabolic pathways associated with CKD progression include arginine and ornithine metabolism, tryptophan metabolism, and the pentose phosphate pathway.Conclusion: By analyzing the metabolic pathways of different metabolites, we have identified the significant impact of CKD progression. The main metabolic pathways involved are Arginine and Ornithine metabolism, Tryptophan metabolism, and Pentose phosphate pathway. ADMA, D-Ornithine, L-Kynurenine, Kynurenic acid, 5-Hydroxyindoleacetic acid, and Gluconic acid could serve as potential early biomarkers for CKD progression. These findings have important implications for the early intervention and treatment of CKD, as well as for further research into the underlying mechanisms of its pathogenesis.Keywords: arginine and ornithine metabolism, tryptophan metabolism, pentose phosphate pathway, biomarkers

Guimin Hou,1,&ast; Feng Zhang,1,&ast; Xielin Feng,1 Yan Chen,2 Jinliang Zhang,1 Haiqing Wang1 1Department of Hepatopancreatobiliary Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2Department of Pharmacy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiqing Wang, Department of Hepatopancreatobiliary Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital and Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China, Tel +86-028-85420945, Email wanghaiqing241286@163.comPurpose: Hepatectomy could provide better survival benefit for hepatocellular carcinoma (HCC) with type I/II portal vein tumor thrombosis (PVTT). However, the postoperative recurrence remains high. We discussed whether neoadjuvant therapy could reduce HCC recurrence for these patients.Patients and Methods: One hundred and thirty-eight resectable HCC with type I–II PVTT were retrospectively included. The neoadjuvant therapy regimens included tyrosine kinase inhibitor (TKI), programmed death 1(PD-1) antibodies and transarterial chemoembolization (TACE). Short-term and long-term outcomes were compared. Propensity score matching (PSM) was performed to minimize the influence of potential confounders.Results: Thirty-three patients underwent neoadjuvant therapy and 105 patients underwent surgery alone. In the neoadjuvant group, 7 (21.2%) patients achieved stable disease, 13 (39.4%) achieved partial response and 13 (39.4%) achieved complete response based on the modified Response Evaluation Criteria in Solid Tumors criterion. By PSM, the neoadjuvant therapy resulted in less microvascular invasion (24.1% vs 50.0%, P=0.021), satellite nodule (6.9% vs 24.1%, P=0.036) and less patients with alpha-fetoprotein> 20(ng/mL) (37.9% vs 69.0%, P=0.006). The neoadjuvant therapy reduced tumor recurrence and prolonged survival. Multivariate analysis found that neoadjuvant therapy was an independent protective factor for overall survival and recurrence free survival.Conclusion: Neoadjuvant treatment presents a promising treatment option for HCC patients with type I/II PVTT.Keywords: hepatocellular carcinoma, neoadjuvant treatment, portal vein tumor thrombosis, TACE, immunotherapy, TKIs

Liang Liu,1 Yan Qian,2 Yanhua Chen1 1Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2School of Social and Public Administration, East China University of Science and Technology, Shanghai, People’s Republic of ChinaCorrespondence: Yanhua Chen, Email chenyh@shspdjw.comBackground: After acute treatment, patients with schizophrenia return to their original living environment for further rehabilitation, which not only determines the quality of life of the patients and their families but also has an important impact on society. However, patients often find it difficult to adapt to changes in the environment when they are discharged from the hospital. This may be related to the incompleteness of China’s mental health service system, as many services for schizophrenia patients are only in the treatment stage. In China, schizophrenia is traditionally associated with poor moral quality, and patients find it difficult to obtain support. Many patients have trouble reintegrating into the community after treatment. Schizophrenic multifamily teams gather families affected by the same illness and pain together to promote healing together in an environment that allows mutual sharing, understanding and transparency, maximizes the use of family resources for support, improves discharge readiness, and better deals with post-discharge recovery.Methods: The multifamily group intervention method was used to improve the motivation of the patients’ family motivation as well as the discharge readiness and self-efficacy of the patient.Results: After the intervention, the motivation of the family and discharge readiness of the patient were improved compared with that of the baseline period; however, the improvement was not significant. The self-efficacy of the patients was significantly improved (P=0.042).Conclusions: In the discharge preparation of schizophrenia patients, multifamily teams can be used to help patients and their families share resources, enhance support and prepare for discharge. Patients will have better support following discharge for recovery in the community. Additional consideration should be given to the impact of the environment on patient services, and the evaluation of the service process is key to continuously improving the service effect.Keywords: schizophrenia multifamily discharge group

Yanwu Zhang,1,&ast; Buasiyamu Abudunaibi,2,&ast; Yunkang Zhao,2 Dongliang Zhang,1 Yanru Chu,1 Song Lei,1 Xiaomin Gu,1 Xuying Lao,1 Xianhao Wu,1 Weitao Yao,1 Yi Chen,1 Feng Tong1 1Department of Infectious Disease Control and Prevention, Ningbo Prefectural Center for Disease Control and Prevention, Ningbo, Zhejiang Province, People’s Republic of China; 2State Key Laboratory of Vaccines for Infectious Diseases, Xiang’ an Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Tong; Yi Chen, Ningbo Prefectural Center for Disease Control and Prevention, Ningbo, Zhejiang Province, People’s Republic of China, Email tongfeng1031@163.com; 30279068@qq.comObjective: To conduct a comprehensive evaluation of the Dengue Fever Surveillance and Early Warning System deployed in Ningbo City during 2023, focusing on its capacity for timely identification and reporting of dengue fever cases, particularly imported cases from endemic regions.Methods: A detailed data of patient clinical features and blood profile trends was collected from clinical records and surveillance reports, focusing on the rapid diagnostic processes and surveillance rigor. This study assessed the effectiveness of the system in identifying and reporting dengue cases and identified the limitations of the existing framework through a basic statistical approach.Results: The system demonstrated timely identification and reporting of dengue fever cases, with a particular emphasis on imported cases. However, several limitations were identified, including the need for more precise monitoring criteria and improved coordination with medical entities.Conclusion: The study underscores the critical role of public health bodies in managing disease outbreaks and advocates for enhanced methodologies to refine epidemic control efforts. The findings contribute to the advancement of early warning mechanisms and the improvement of proactive infectious disease monitoring in metropolitan environments, providing valuable insights for fortifying the Dengue Fever Surveillance and Early Warning System in Ningbo City.Keywords: Dengue fever, Imported, Surveillance, Early-warning

Jiankang Wu,1– 4 Yan Chen1– 4 1Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, People’s Republic of China; 3Clinical Medical Research Center for Pulmonary and Critical Care Medicine, Changsha, Hunan, People’s Republic of China; 4Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Yan Chen, Email chenyan99727@csu.edu.cnAbstract: Extracellular vesicles (EVs) are nanoscale lipid bilayer vesicles released during cell activation, cellular damage, or apoptosis. They carry nucleic acids, proteins, and lipids facilitating intercellular communication and activate signaling pathways in target cells. In non-small cell lung cancer (NSCLC), EVs may contribute to tumor growth and metastasis by modulating immune responses, facilitating epithelial-mesenchymal transition, and promoting angiogenesis, while potentially contributing to resistance to chemotherapy drugs. EVs in liquid biopsies serve as non-invasive biomarkers for early cancer detection and diagnosis. Due to their small size, inherent molecular transport properties, and excellent biocompatibility, EVs also act as natural drug delivery vehicles in NSCLC therapy. Keywords: extracellular vesicles, non-small cell lung cancer, immunity, metastasis, drug, biomarkers

Lantian Xie,1,&ast; Yan Chen,1,&ast; Lifan Zhang,1– 3 Lidan Zhao,4 Tao Li,5 Xiaochun Shi,1,2 Xiaoqing Liu1– 3 1Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Clinical Epidemiology Unit, Peking Union Medical College, International Clinical Epidemiology Network, Beijing, People’s Republic of China; 4Department of Rheumatology and Clinical Immunology, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Psychological Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaochun Shi; Xiaoqing Liu, Email shixch7722@163.com; liuxq@pumch.cnObjective: Tuberculosis preventive treatment (TPT) is an important strategy for tuberculosis (TB) control. Rheumatic diseases (RD) patients are at high risk for active TB development. More researches are needed in terms of patient compliance in clinical practice. This study aims to explore the potential difficulties and obstacles in latent tuberculosis infection (LTBI) screening and TPT in RD patients.Methods: Convenience sampling was used to recruit RD outpatients who had indications for LTBI screening and TPT. All participants were given questionnaires on knowledge and attitudes regarding screening and preventive treatment of LTBI.Results: Of the 200 RD patients, most people were aware that they were at increased risk of ATB due to their rheumatic disease and knew that TB was curable. The main association with willingness to have screening for LTBI was tertiary education (P = 0.013). The main association with willingness to take treatment for LTBI was a sense of personal risk and belief that the treatment would reduce risk of ATB (P < 0.001). More than half of the people surveyed could not accept taking 6 or more pills per day, while more than half of the patients could tolerate a treatment course of 9 months or longer. Most (65.4%) preferred their own rheumatologists to initiate treatment.Conclusion: Educating RD patients about their individual risks of TB and the side effects of treatment, and educating/empowering rheumatologists to discuss these aspects with their patients and to offer LTBI screening and treatment, may help improve patients′ compliance with LTBI screening and TPT.Keywords: rheumatic diseases, latent tuberculosis infection, tuberculosis preventive treatment, knowledge, attitudes

Yu Qiu,1,2,&ast; Yan Chen,1,2,&ast; Haoyang Shen,1,2 Shuixin Yan,1,2 Jiadi Li,1,2 Weizhu Wu1 1The Affiliated Lihuili Hospital, Ningbo University, Ningbo, 315000, People’s Republic of China; 2Health Science Center, Ningbo University, Ningbo, Zhejiang, 315000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weizhu Wu, The Affiliated Lihuili Hospital, 1111 Jiangnan Road, Ningbo, Zhejiang, 315000, People’s Republic of China, Tel +86 574 13957402451, Email wuweizhu1128@163.comPurpose: This study investigated the correlation between the Naples prognostic score (NPS), clinicopathological traits, and the postoperative prognoses of patients with triple-negative breast cancer (TNBC). Based on NPS, a predictive nomogram was developed to estimate the long-term survival probabilities of patients with TNBC post-surgery.Patients and Methods: We retrospectively examined the clinical records of 223 women with TNBC treated at Ningbo Medical Center, Lihuili Hospital between January 1, 2016 and December 31, 2020. Blood tests and biochemical analyses were conducted before surgery. The prognostic nutritional index (PNI), controlling nutritional status (CONUT), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and NPS were determined based on blood-related markers. A Kaplan-Meier survival analysis assessed the association between NPS, PNI, CONUT score, overall survival (OS), and breast cancer-specific survival (BCSS). Predictive accuracy was evaluated using the area under the receiver operating characteristic curve (AUC) and C index. The patients were randomly divided into the training and the validation group (6:4 ratio). A nomogram prediction model was developed and evaluated using the R Software for Statistical Computing (RMS) package.Results: NPS outperformed other scores in predicting inflammation outcomes. Patients with an elevated NPS had a poorer prognosis (P< 0.001). Lymph node ratio (LNR), surgical method, postoperative chemotherapy, and NPS independently predicted OS, whereas M stage, LNR, and NPS independently predicted BCSS outcome. The OS and BCSS predicted by the nomogram model aligned well with the actual OS and BCSS. The decision curve analysis showed significant clinical utility for the nomogram model.Conclusion: In this study, NPS was an important prognostic indicator for patients with TNBC. The nomogram prognostic model based on NPS outperformed other prognostic scores for predicting patient prognosis. The model demonstrated a clear stratification ability for patient prognosis, which emphasized the potential benefits of early intervention for high-risk patients.Plain Language Summary: In this study, we aimed to understand how the Naples prognostic score (NPS) scoring system could predict the prognosis for patients with triple-negative breast cancer (TNBC). TNBC is a type of breast cancer that can be difficult to treat. Medical records of 223 women with TNBC were retrospectively analyzed. These women had their blood tested before surgery to check for certain markers related to nutrition and inflammation. NPS was used along with other scores to determine their accuracy in predicting survival. NPS was better at predicting outcomes than the other scores. The patients with higher NPS scores tended to have poorer outcomes. We also created a visual tool called a nomogram to help doctors predict patient outcomes based on the NPS scores. NPS can be a valuable tool for doctors treating patients with TNBC because it can help them predict how well a patient might do after surgery. This information could be used to tailor treatment plans for these patients. The nomogram provides a user-friendly way for doctors to use NPS in their practice. Overall, this study showed that NPS is a powerful tool for predicting outcomes for patients with TNBC, which could lead to better treatment decisions and improved outcomes for these patients.Keywords: triple-negative breast cancer, Naples prognostic score, prognostic factor, nomogram predictive model

Pengfeng Gong,1,&ast; Jie Shen,1 Yu Yang,2,&ast; Dong Xue,1 Hao Lu,1 Qianfeng Zhuang,1 Xiaogang Wang,1 Zinong Tian,1 Yiming Chen,1 Cheng Chen,1 Yunjie Cao1 1Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213000, People’s Republic of China; 2Department of Hepato-Pancreato-Biliary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunjie Cao, Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213000, People’s Republic of China, Tel +86-13775188220, Email caoyunjie1847@163.comObjective: To explore patients’ knowledge, attitude, and practice (KAP) toward varicocele in China and the relationship between treatment selection and KAP.Methods: This cross-sectional study enrolled varicocele patients at the Third Affiliated Hospital of Soochow University (September to October 2023). Structural equation modeling (SEM) was used to explore the relationship between clinical factors and KAP. A score >mean score for each dimension was defined as adequate knowledge, positive attitude, and proactive practice. The patients were grouped according to varicocelectomy vs no surgery. Univariable and multivariable logistic regression analyses were used to identify the factors independently associated with KAP. A structural equation modeling (SEM) analysis was performed to examine how the KAP dimensions influenced each other.Results: Among 502 patients, 44.02%, 35.86%, and 20.12% were ≤ 30, 31– 40, and > 40 years old, respectively. Those who underwent varicocelectomy (n=407) had significantly higher knowledge (20 (15– 22) vs 0 (0– 6), P< 0.001), attitude (26 (24– 26) vs 14 (10– 18), P< 0.001), and practice (20 (17– 24) vs 8 (6– 16), P< 0.001) than those who did not. A higher proportion of patients with varicocelectomy were < 40 years old, more educated, had higher income, and were unmarried compared with those without surgery (all P< 0.001). High school or higher education level and varicocelectomy (irrespective of type) were independently associated with adequate knowledge (all P< 0.001). Knowledge, college/bachelor’s degree education, and varicocelectomy type (irrespective of type) were associated with positive attitudes (all P< 0.05). In the SEM, knowledge directly influenced attitude, knowledge directly influenced practice, and attitude directly influenced practice (all P< 0.001). Having knowledge of the subject may direct varicocele patients to varicocelectomy.Conclusion: Chinese patients who underwent varicocelectomy exhibit appropriate KAP regarding varicocele, while non-surgery patients have poorer KAP. These results suggest that patients who did not undergo surgery should nevertheless be properly informed about their disease.Keywords: knowledge, attitude, practice, varicocele, varicocelectomy, cross-sectional study

Dongdong Li,1 Lijun Bian,1 Lili Cui,2 Jingying Zhou,1 Gaotian Li,1 Xiaoyan Zhao,1 Liao Xing,1 Jiaxing Cui,1 Bo Sun,1 Chunlai Jiang,1,3,4 Wei Kong,1,3,4 Yong Zhang,1,3,4 Yan Chen1,3,4 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 2Beijing Institute of Drug Metabolism, Beijing, People’s Republic of China; 3Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 4NMPA Key Laboratory of Humanized Animal Models for Evaluation of Vaccines and Cell Therapy Products, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yan Chen; Yong Zhang, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China, Tel +86-431-85167751, Fax +86-431-85167674, Email chen_yan0417@126.com; zhypharm@jlu.edu.cnPurpose: Heterologous immunization using different vaccine platforms has been demonstrated as an efficient strategy to enhance antigen-specific immune responses. In this study, we performed a head-to-head comparison of both humoral and cellular immune response induced by different prime-boost immunization regimens of mRNA vaccine and adjuvanted protein subunit vaccine against varicella-zoster virus (VZV) in middle-aged mice, aiming to get a better understanding of the influence of vaccination schedule on immune response.Methods: VZV glycoprotein (gE) mRNA was synthesized and encapsulated into SM-102-based lipid nanoparticles (LNPs). VZV-primed middle-aged C57BL/6 mice were then subjected to homologous and heterologous prime-boost immunization strategies using VZV gE mRNA vaccine (RNA-gE) and protein subunit vaccine (PS-gE). The antigen-specific antibodies were evaluated using enzyme-linked immunosorbent assay (ELISA) analysis. Additionally, cell-mediated immunity (CMI) was detected using ELISPOT assay and flow cytometry. Besides, in vivo safety profiles were also evaluated and compared.Results: The mRNA-loaded lipid nanoparticles had a hydrodynamic diameter of approximately 130 nm and a polydispersity index of 0.156. Total IgG antibody levels exhibited no significant differences among different immunization strategies. However, mice received 2×RNA-gE or RNA-gE>PS-gE showed a lower IgG1/IgG2c ratio than those received 2×PS-gE and PS-gE> RNA-gE. The CMI response induced by 2×RNA-gE or RNA-gE>PS-gE was significantly stronger than that induced by 2×PS-gE and PS-gE> RNA-gE. The safety evaluation indicated that both mRNA vaccine and protein vaccine induced a transient body weight loss in mice. Furthermore, the protein vaccine produced a notable inflammatory response at the injection sites, while the mRNA vaccine showed no observable inflammation.Conclusion: The heterologous prime-boost strategy has demonstrated that an mRNA-primed immunization regimen can induce a better cell-mediated immune response than a protein subunit-primed regimen in middle-aged mice. These findings provide valuable insights into the design and optimization of VZV vaccines with the potentials to broaden varicella vaccination strategies in the future.Keywords: varicella-zoster Virus, mRNA vaccine, glycoprotein E, lipid nanoparticles, heterologous prime-boost, cell-mediated immunity

Xijing Yu,1,&ast; Yaqin Chen,1,&ast; Yanchun Peng,2 Liangwan Chen,3,4 Yanjuan Lin2,3 1School of Nursing, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Department of Nursing, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 3Department of Cardiac Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 4Key Laboratory of Cardio-Thoracic Surgery, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanjuan Lin, Department of Nursing, Union Hospital, Fujian Medical University, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86059186218336, Fax +86059183344034, Email fjxhyjl@163.com Liangwan Chen, Department of Cardiac Surgery, Union Hospital, Fujian Medical University, No. 29 Xinquan Road, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86059186218336, Fax +86059183301393, Email fjxhlwc@163.comPurpose: The inflammatory response of the body is intimately linked to the quick onset and high in-hospital mortality of Acute Type A Aortic Dissection (ATAAD). The purpose of the study was to examine the connection between in-hospital mortality in patients with ATAAD upon admission and the Pan-Immune-Inflammation Value (PIV).Patients and Methods: 308 patients who were diagnosed with ATAAD between September 2018 and October 2021 at Fujian Provincial Center for Cardiovascular Medicine had their clinical data retrospectively examined. PIV was assessed at the time of study population admission, with in-hospital mortality serving as the main outcome measure. Patients were divided into two groups, the high PIV group (PIV > 1807.704) and the low PIV group (PIV < 1807.704), based on the PIV ROC curve and the best threshold of the Youden index. The clinical results of the two groups were then compared.Results: Among ATAAD patients, postoperative in-hospital mortality was higher in the high PIV group (54.7% vs 10.6%, P < 0.001), and the high PIV group had significantly higher rates of postoperative acute kidney injury, acute liver insufficiency, and gastrointestinal hemorrhage (P < 0.05). Additionally, the high PIV group’s ICU stays lasted longer than the low PIV group’s (P < 0.05). The results of multifactorial logistic regression analysis, which controlled for other variables, indicated that the mechanical ventilation time (OR = 1.860, 95% CI: 1.437, 2.408; P < 0.001), the high PIV group (> 1807.704) (OR = 1.939, 95% CI: 1.257, 2.990; P = 0.003), the cardiopulmonary bypass time (OR = 1.011, 95% CI: 1.004, 1.018; P = 0.002), and the white blood cell count (OR = 1.188, 95% CI: 1.054, 1.340; P = 0.005) were independent risk factors for postoperative in-hospital mortality in ATAAD patients.Conclusion: Postoperative death in ATAAD patients was independently predicted by high PIV levels at admission. Patients should be informed about their preoperative inflammatory status and actively participate in prompt clinical decision-making and treatment.Keywords: Acute Type A Aortic Dissection, the Pan-Immune-Inflammation Value, Inflammation, Cardiac surgery, In-hospital mortality

Xiaoyan Huang,&ast; Liqun Li,&ast; Chaowei Zheng, Jianfeng Li, Guangwen Chen, Yalu Chen Department of Gastroenterology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning City, Guangxi Zhuang Autonomous Region, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyan Huang, Department of Gastroenterology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, 89-9 Dongge Road, Qingxiu District, Nanning City, Guangxi Zhuang Autonomous Region, 530023, People’s Republic of China, Tel +00867715667460, Email hxy763616@163.comBackground: Ulcerative colitis (UC), a highly relapsing non-specific disease, is difficult to cure completely. The investigation aims to determine the protective effect and potential action mechanism of Xuanbi yuyang decoction (XBD) on UC.Methods: The chemical composition of XBD was determined through non-targeted metabolomics analysis. Subsequently, experimental mice were orally given 3% DSS for 6 days, followed by XBD treatment (0.3 mL, 0.4 mL). In vitro, the human colon epithelial cells were co-treated with DSS and medicated serum. The therapeutic effects of XBD on UC were evaluated in vivo and vitro. The mechanisms of XBD against UC were determined by detecting hallmarks related to pyroptosis and Interleukin (IL)-17 pathways using Western blot and ELISA. The recombinant human interleukin 17A (rhIL17A) and was applied for further verifying the effect of XBD on IL-17 pathway in UC cells.Results: XBD supplementation restored DSS-induced weight loss, colon shortening and tissue damage, and reduced DAI. Moreover, XBD enhanced viability, repaired the intestinal mucosal barrier of colitis, decreased pro-inflammatory cytokines levels, and inhibited pyroptosis. Additionally, DSS increased the expression of IL-17 pathway was and cytokines (IL-17A, IL-6), which were blocked by XBD treatment. The rhIL17A treatment attenuated protective effect against DSS-induced colitis and could also enhance pyroptosis.Conclusion: XBD has a favorable protective effect against DSS-induced colitis through restraining pyroptosis via inhibition of IL-17 signaling pathway activation, suggesting XBD may be a new and effective treatment therapy for UC.Keywords: ulcerative colitis, Xuanbi yuyang decoction, pyroptosis, IL-17 pathway, inflammation

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

Yue Xu,1,&ast; Shuhong Zhang,1,&ast; Ping Wang,1,&ast; Yuanyuan Chen,1 Yazhan Mao,2 Xina Yuan,3 Yinyi Li,4 Mingming Li,1 Li Sheng,1 Xiaoqian Li,1 Na Gao1 1Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Respiratory, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China; 3College of Pulmonary and Critical Care Medicine, The Eighth Medical Center, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China; 4Department of Outpatient, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Na Gao; Xiaoqian Li, Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China, Tel +86 18515165409, Email gaona301s@163.com; 41705763@qq.comObjective: This study aims to explore the correlates of frailty in hospitalized elderly hypertensive patients and its impact on clinical prognosis, and to construct a predictive model for the occurrence of frailty in this population.Methods: A cross-sectional and prospective observational cohort study was conducted, involving 312 elderly hypertensive patients diagnosed at the institution from January to June 2022. Frailty was diagnosed using the Fried Frailty Phenotype (FP), while the Charlson Comorbidities Index (CCI) assessed the presence of chronic conditions. Data analysis was performed using SPSS 22.0. Binary logistic regression analysis was conducted with frailty as the dependent variable to identify risk factors. Patients were followed for one year to monitor readmission rates and all-cause mortality.Results: Multivariate logistic regression identified CCI grade (P=0.030), gender (OR=21.618, 95% CI: 4.062– 115.061, P < 0.001), age (OR=1.147, 95% CI: 1.086– 1.211, P < 0.001), bedridden state (OR=11.620, 95% CI: 3.282– 41.140, P < 0.001), arrhythmia (OR=14.414, 95% CI: 4.558– 45.585, P < 0.001), heart failure (OR=5.439, 95% CI: 1.029– 28.740, P < 0.05), along with several biochemical markers, as independent predictors of frailty. A predictive model was developed, demonstrating a robust discriminative ability with an area under the receiver operating characteristic curve (AUC) of 0.915. Statistically significant differences in readmission rates and all-cause mortality were observed among the frail, pre-frail, and non-frail groups (P< 0.001), with the frail group exhibiting the highest incidence of these adverse outcomes. Notably, frailty emerged as a significant predictor of readmission (P< 0.05) but not of all-cause mortality in this cohort.Conclusion: This study establishes a robust frailty prediction model for elderly hypertensive patients, highlighting the influence of CCI grade, gender, age, and other clinical and biochemical factors on frailty. The model offers a valuable tool for healthcare providers to identify at-risk elderly individuals, facilitating targeted intervention strategies for cardiovascular disease management.Keywords: frailty, hypertension, older people, observational study, prediction model

Xiaoming Zhou,1 Weiwei Shen,1 Jue Zhu,2 Yichen Chen,2 Jing Zhang2 1Department of Gynecology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, People’s Republic of China; 2Department of Gynecology, Ningbo Women & Children’s Hospital, Ningbo, Zhejiang, 315010, People’s Republic of ChinaCorrespondence: Jing Zhang, Department of Gynecology, Ningbo Women & Children’s Hospital, 339 Liuting Street, Haishu District, Ningbo, 315010, Zhejiang, People’s Republic of China, Tel +86-15867877000, Email jzhang_nbdr@outlook.comPurpose: To investigate the association between the oxidative balance score (OBS) and endometriosis.Methods: This cross-sectional study used four cycles of the National Health and Nutrition Examination Survey (NHANES) (1999– 2000, 2001– 2002, 2003– 2004, and 2005– 2006). OBS involved 16 dietary nutrients and 4 lifestyle factors, including 5 pro-oxidants and 15 anti-oxidants. According to weighted quartiles, the OBS was divided into four categories: < 12.54, 12.54– 18.70, 18.71– 24.68, and > 24.68. Endometriosis was diagnosed based on a question from the reproductive health questionnaire. Weighted multivariate logistic analysis was used to investigate the association between OBS and endometriosis. Subgroup analysis was performed based on menstrual regularity and female hormone use.Results: A total of 5095 women were included, with 1140 (22.37%), 1232 (24.18%), 1224 (24.02%), and 1499 (29.42%) women in the OBS < 12.54, of 12.54– 18.70, of 18.71– 24.68, and > 24.68 categories, respectively. After adjusting age, race, family poverty-to-income ratio (PIR), education level, uterine fibroids, menstrual regularity, oophorectomy, female hormone use, hypertension, dyslipidemia, and steroid drug, a high OBS (> 24.68) was found to be associated with lower odds of endometriosis [odds ratio (OR) = 0.70, 95% confidence interval (CI): 0.50– 0.97, P = 0.033] compared to a low OBS (< 12.54). The similar result was also found in women with irregular menstruation (OR = 0.58, 95% CI: 0.37– 0.91, P = 0.020) and with female hormone use (OR = 0.71, 95% CI: 0.52– 0.98, P = 0.037).Conclusion: A high OBS was associated with lower odds of endometriosis, especially in women with irregular menstruation and female hormone use.Keywords: Oxidative balance score, endometriosis, menstruation, female hormones, NHANES

Yuanping Chen,1 Chao Liu,1 Xinglin Wen,2 Chen Wang,1 Jing He1 1Department of Oncology, Ganzhou People’s Hospital, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, People’s Republic of China; 2Department of Medical Image, Ganzhou People’s Hospital, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, People’s Republic of ChinaCorrespondence: Jing He, Department of Oncology, Ganzhou People’s Hospital, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, 341000, People’s Republic of China, Tel +86_15297720705, Email 382505721@qq.comAbstract: Breast cancer with brain metastasis accounts for the second largest number of brain metastases among solid malignancies. Despite advances in HER2-targeted therapy, 50% of patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer develop brain metastases and are associated with poor outcomes. In this article, we report the case of a patient with HER2+ metastatic breast cancer who developed brain metastases, despite experiencing a durable effect on extracranial metastases after treatment with trastuzumab and pertuzumab. The patient exhibited intracranial progression while receiving treatment with trastuzumab deruxtecan monotherapy after secondary brain radiotherapy and multiple lines of therapy with anti-HER2 agents, such as pyrotinib, lapatinib, tucatinib, and ado-trastuzumab emtansine. However, the administration of anlotinib (an antiangiogenesis medication) and trastuzumab deruxtecan resulted in intracranial and extracranial partial response and was linked to manageable side effects. The present case indicates that the combination of anlotinib and trastuzumab deruxtecan may be a promising treatment option for patients with HER2+ breast cancer with brain metastasis. Nevertheless, further studies are warranted to verify the present findings.Keywords: HER2 positive, breast cancer, brain metastases, anlotinib, trastuzumab deruxtecan

Qian Zeng,1 Lu Liu,1 Ying Chen,1 Daohong Chen,1 Ziyang Zhou,1 Wenjiao Hu,1 Siyao Gong,1 Bin He,1 Wenchuan Qi,1,2 Chao Wang,1,3 Zuoqin Yang,4 Shuguang Yu,1,2 Ling Zhao1,2 1Department of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Key Laboratory of Acupuncture for Senile Disease, Chengdu University of Traditional Chinese Medicine, Ministry of Education, Chengdu, People’s Republic of China; 3Sub-health Management Center, Sichuan Integrative Medicine Hospital, Chengdu, People’s Republic of China; 4Department of Acupuncture and Tuina, Chengdu Pidu District Hospital of Traditional Chinese Medicine, Sichuan, People’s Republic of ChinaCorrespondence: Ling Zhao, Department of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, 1166 Liutai Avenue, Wenjiang District, Chengdu City, Sichuan Province, 611137, People’s Republic of China, Tel +86 28 6180 0000, Email zhaoling@cdutcm.edu.cnBackground: Acupuncture has been used as an adjuvant therapy for Chronic obstructive pulmonary disease (COPD). However, systematic reviews (SRs) and meta-analyses (MAs) have reported inconsistent results and unknown quality. This overview aimed to summarize the current SRs/MAs to provide evidence for the effectiveness and safety of acupuncture in the treatment of COPD.Methods: SRs/MAs were searched via eight databases from their establishment to December 31, 2023. The methodological quality was assessed by A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The risk of bias was assessed using the Risk of Bias in Systematic Review (ROBIS) tool. The Preferred Reporting Items for Systematic Reviews and Meta-analyses for Acupuncture (PRISMA-A) to evaluate the reporting quality. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to determine the strength of evidence. In addition, we also conducted an analysis of the acupuncture points used in the primary RCTs.Results: Twenty-two SRs/MAs were included in this overview. Based on the assessment using AMSTAR 2, nineteen SRs/MAs were “critically low”. Eight SRs/MAs had a low risk of bias. Based on PRISMA-A, the reporting completeness of eighteen SRs/MAs were more than 70%. As for GRADE assessment, only three outcome measures were of high quality. COPD patients can benefit from moxibustion, acupoint application, acupoint catgut embedding, manual acupuncture, and electroacupuncture, as indicated by effectiveness in measures including lung function, 6MWD, mMRC, CAT, and acute exacerbation. In addition, the efficacy of TENS needed to be further demonstrated. The commonly used acupuncture points in the RCTs include BL13, BL23, and EX-B1.Conclusion: Evidence from SRs showed that acupuncture is beneficial to lung function, acute exacerbation, 6MWD, mMRC and CAT. For SGRQ and brog scale, acupuncture should be used selectively, but this finding should still be taken with caution.Keywords: acupuncture, COPD, systematic reviews, overview

Kaifei Chu,1,2,&ast; Jie Liu,2,&ast; Xu Zhang,1,2 Minran Wang,1 Wanping Yu,1 Yuyue Chen,1 Lingling Xu,2 Geng Yang,1 Naru Zhang,1 Tiejun Zhao1,2 1Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, People’s Republic of China; 2College of Life Sciences, Zhejiang Normal University, Jinhua, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tiejun Zhao; Naru Zhang, Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, 310015, People’s Republic of China, Email tjzhao@hzcu.edu.cn; zhangnr@hzcu.edu.cnAbstract: Plant-derived exosome-like nanovesicles (PDNVs) are small nanoscale vesicles containing lipids, RNAs, proteins and some plant natural products secreted by plant cells. Over the last decade, PDNVs have garnered significant interest due to its exceptional therapeutic benefits in the treatment of various diseases. Herbal medicine, as a medicinal plant, plays an important role in the treatment of diseases including cancer. Especially in recent years, the function of herbal medicine derived exosome-like nanovesicles (HMDNVs) in the treatment of cancer has been widely concerned, and has become a research hotspot of nanomedicine. In this review, the biological characteristics, functions and the therapeutic advantages of PDNVs are reviewed, as well as the recent achievements and research progress of HMDNVs in cancer treatment, demonstrating its enormous promise as a cancer therapy, and new insights are provided for future research and development of anti-tumor drugs.Keywords: herbal medicine, plant-derived exosome-like nanovesicles, extracellular vesicles, cancer treatment, nanomedicine

Yuqing Li,1,&ast; Lei Wu,1,2,&ast; Rui Zhao,1,2,&ast; Yi Gao,1 Geng Bai,1 Ziqiang Guo,1 Xiaolin Chen,1 Yuanlu Chen,2 Tong Liu,1 Guangping Li1 1Tianjin Key Laboratory of Logic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China; 2TEDA International Cardiovascular Hospital, Electrophysiological Department, Tianjin, 300457, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangping Li, Email tic_tjcardiol@126.comBackground: An electrocardiogram (ECG) was used to determine the type of acute myocardial infarction (MI) and locate the culprit vessel. Inferior wall myocardial infarction (IWMI) patients with the right coronary artery (RCA) as the culprit vessel may have a worse clinical prognosis than the left circumflex artery (LCx). We aimed to develop a new, simple, accurate scoring system to localize the RCA.Methods: From January 2018 to January 2020, patients were admitted to the Department of Cardiology of TEDA International Cardiovascular Hospital and the Second Hospital of Tianjin Medical University due to IWMI and coronary angiography confirmed that the infarct-related vessel was a single RCA or LCx. ECG of patients before percutaneous coronary intervention (PCI) was collected to quantitatively analyze the characteristics of ST-segment deviation in non-inferior wall leads (N-IWL) and establish the RCA score in N-IWL.Results: 149 patients were enrolled, including 83 in the RCA group and 66 in the LCx group. Finally, ST-segment depression (ST↓) lead I, aVR, V1, and V6, and ST↓≥ 1mm in lead V4 were found to be associated with the location of the RCA. The sensitivity, specificity, and area under the curve (AUC) of the N-IWL RCA scoring system were 77.1%, 72.7%, and 0.83, respectively. The diagnostic ability of the scoring system was better than that of other algorithms and scoring systems.Conclusion: ECG helps identify the RCA in patients with IWMI before PCI. The N-IWL RCA score may help identify the culprit vessel as the RCA in patients with IWMI.Keywords: electrocardiogram, inferior wall myocardial infarction, percutaneous coronary intervention, right coronary artery

Yi Shao,&ast; Yunfu Chen,&ast; Xin Lan, Jun Lu, Guangling Tang, Sijie Tang, Ruixue Zhai, Chao Chen, Xinglong Xiong, Jing Shi Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Shi, Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, No. 28 Beijing Road, Guiyi Street, Yunyan District, Guiyang, Guizhou, 550001, People’s Republic of China, Tel +86-18685034016, Email shijing81@gmc.edu.cnBackground: Morin can alleviate vincristine-induced neuropathic pain via inhibiting neuroinflammation. Microglial cells play an important role in initiating and maintenance of pain and neuroinflammation. It remains unclear whether morin exerts antinociceptive properties through the regulation of microglial cells. This study aimed to elucidate the mechanisms of morin against neuropathic pain focusing on microglial cells.Methods: The thermal withdrawal latency and mechanical withdrawal threshold were used as measures of pain behaviours. Histological abnormalities of the sciatic nerve were observed with transmission electron microscopy. The sciatic functional index and the sciatic nerve conduction velocity were used as measures of the functional deficits of the sciatic nerve. Inflammatory factors were detected using ELISA. The expression of M1/M2 polarization markers of microglia and nuclear factor κB (NF-κB) p65 were measured by immunofluorescence, real-time quantitative PCR and Western blotting.Results: Morin alleviated vincristine-induced abnormal pain, sciatic nerve injury, and neuroinflammatory response in rats. Furthermore, morin decreased the expression of NF-κB P65 and M1 activation markers, increased the expression of M2 activation markers. Additionally, phorbol 12-myristate 13-acetate reversed the effects of morin on microglial polarization, the production of inflammatory factors and neuropathic pain, while ammonium pyrrolidine dithiocarbamate showed the opposite effects.Conclusion: Our results demonstrate that morin inhibits neuroinflammation to alleviate vincristine-induced neuropathic pain via inhibiting the NF-κB signalling pathway to regulate M1/M2 microglial polarization.Keywords: neuropathic pain, morin, microglia, NF-κB, neuroinflammation

Jiayi Chen,1,&ast; Yonghong Liu,2,&ast; Shengsheng Huang,1 Zixiang Pang,1 Qian Wei,1 Yuzhen Liu,1 Hongyuan Qin,1 Yuanming Chen1 1Department of Spinal Orthopedics, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Preventive Health Care, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanming Chen, Department of Spinal Orthopedics, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China, Email rkyygk@163.comIntroduction: This study evaluates the efficacy of metagenomic next-generation sequencing (mNGS) in diagnosing spinal infections and developing therapeutic regimens that combine mNGS, microbiological cultures, and pathological investigations.Methods: Data were collected from 108 patients with suspected spinal infections between January 2022 and December 2023. Lesion tissues were obtained via C-arm assisted puncture or open surgery for mNGS, conventional microbiological culture, and pathological analysis. Personalized antimicrobial therapies were tailored based on these findings, with follow-up evaluations 7 days postoperatively. The sensitivity and specificity of mNGS were assessed, along with its impact on treatment and prognosis.Results: mNGS showed a significantly higher positive detection rate (61.20%) compared to conventional microbiological culture (30.80%) and PCT (28%). mNGS demonstrated greater sensitivity (79.41%) and negative predictive value (63.16%) than cultures (25% and 22.58%, respectively), with no significant difference in specificity and positive predictive value. Seven days post-surgery, a significant reduction in neutrophil percentage (NEUT%) was observed, though decreases in white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were not statistically significant. At the last follow-up, significant improved in Visual Analogue Scale (VAS) scores, Oswestry Disability Index (ODI), and Japanese Orthopaedic Association (JOA) scores were noted.Conclusion: mNGS outperforms traditional microbiological culture in pathogen detection, especially for rare and critical pathogens. Treatment protocols combining mNGS, microbiological cultures, and pathological examinations are effective and provide valuable clinical insights for treating spinal infections.Keywords: spinal infection, metagenomic next-generation sequencing, sensitivity, specificity treatment

Hao Hong,1 Junyao Zheng,2 Haimin Shi,2 Suya Zhou,3 Yue Chen,4 Ming Li2 1Department of Intensive Care Unit, The First Affiliated Hospital of Soochow University, Soochow, People’s Republic of China; 2Laboratory Nephrology, The First Affiliated Hospital of Soochow University, Soochow, People’s Republic of China; 3Laboratory Nephrology, Jinshan Hospital of Fudan University, Shanghai, People’s Republic of China; 4Laboratory Nephrology, The First People’s Hospital of Kunshan, Soochow, People’s Republic of ChinaCorrespondence: Ming Li, Email 1925924373@qq.comPurpose: Changes in inflammation, immunity, and nutritional status can promote the development of chronic kidney disease (CKD), and the Naples prognostic score (NPS) reflects changes in these three general clinical parameters. Indoleamine 2.3-dioxygenase (IDO) can block the function of inflammatory cells and inhibit the production of inflammatory cytokines. We examined use of the NPS and IDO activity to predict early-stage CKD.Patients and Methods: Clinical and demographic parameters and the NPS were recorded for 47 CKD patients and 30 healthy controls. A one-way ANOVA or the rank sum test was used to compare variables in the different groups. Spearman or Pearson correlation coefficients were calculated, and logistic regression was used to identify significant factors. Receiver operating characteristic (ROC) analysis was also performed.Results: The NPS had a positive correlation with plasma IDO activity and IDO activity was lowest in controls, and increased with CKD stage. ROC analysis indicated that NPS had an area under the curve (AUC) of 0.779 when comparing controls with all CKD patients. A prediction model for CKD (− 4.847 + [1.234 × NPS] + [6.160 × plasma IDO activity]) demonstrated significant differences between controls and patients with early-stage CKD, and for patients with different stages of CKD. This model had AUC values of 0.885 (control vs CKD1– 4), 0.876 (control vs CKD2), 0.818 (CKD2 vs CKD3), and 0.758 (CKD3 vs CKD4).Conclusion: A prediction model based on the NPS and IDO provided good to excellent predictions of early-stage CKD.Keywords: inflammation, immune, nutrition, score, metabolomic, kynurenine pathway

Wentao Luo,1 Xiuwen Lin,1 Yuchong Chen,2 Wenfeng Luo,3 Huagen Zhang1 1The Third Department of Critical Care Medicine, Meizhou People’s Hospital, Meizhou, Guangdong, 514000, People’s Republic of China; 2The Fourth Department of Critical Care Medicine, Meizhou People’s Hospital, Meizhou, Guangdong, 514000 People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Meizhou People’s Hospital, Meizhou, Guangdong, 514000, People’s Republic of ChinaCorrespondence: Huagen Zhang, The Third Department of Critical Care Medicine, Meizhou People’s Hospital, Meizhou, Guangdong, 514000, People’s Republic of China, Tel +8613549175546, Email 672825592@qq.comBackground: Metagenomic next-generation sequencing (mNGS) is a high-throughput sequencing technique that identifies a wide array of pathogens directly from clinical specimens. This study evaluates the diagnostic value of mNGS in Pneumocystis jirovecii pneumonia (PJP) and compares its efficacy with traditional detection methods, including Grocott’s Methenamine Silver (GMS) staining, serum (1– 3)-β-D-Glucan (BDG) testing, and Lactate Dehydrogenase (LDH) testing.Methods: Seventy-eight patients hospitalized between January 2022 and March 2023 with suspected pulmonary infections were included. Patients were eligible for mNGS if they exhibited symptoms such as fever, cough, dyspnea, or progressive hypoxemia, and met specific clinical criteria for PJP. Specimens obtained included bronchoalveolar lavage fluid, sputum, and peripheral blood. Positive rates and pathogen distributions detected by mNGS and traditional methods were compared.Results: In the PJP group, 25%, 37.5%, and 9.38% of patients had solid organ tumors, corticosteroid use, and skin diseases, respectively, significantly higher than in the non-PJP group. The sensitivity and specificity of mNGS were both 100%, significantly higher than those of serum BDG (sensitivity 50%, specificity 81.8%) and LDH (sensitivity 9.3%, specificity 91.3%). Significant differences in microbial composition between the PJP and Non-PJP groups were observed. mNGS detected multiple mixed pathogens in 96.88% of PJP cases, with 68.75% exhibiting mixed bacterial and viral infections. Notably, 71% of patients improved following antibacterial treatment based on mNGS results.Conclusion: mNGS technology shows superior sensitivity and specificity in diagnosing PJP and guides precise treatment for complex pulmonary infections.Keywords: mNGS, Pneumocystis jirovecii pneumonia, pulmonary infections, dominant pathogens, sensitivity

Huishan Zhang,1,2,&ast; Jing Lin,3,4,&ast; Yufang Huang,3,4 Yu Chen3,4 1Department of Phase I Clinical Trial Ward, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China; 2Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China; 3Department of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China; 4Cancer Bio-Immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Chen, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, 420 Fuma Road, Fuzhou, Fujian, 350014, People’s Republic of China, Tel +86-62752224 Ext 0596, Email chenyu1980@fjmu.edu.cnPurpose: Patients with locally advanced esophageal squamous cell carcinoma (ESCC) scheduled for neoadjuvant radiotherapy still have a poor prognosis. This study was to explore the prognostic value of the pretreatment systemic immune-inflammation index (SII) in patients with locally advanced ESCC after neoadjuvant radiotherapy (NRT).Materials and Methods: Eighty-two consecutive patients with ESCC scheduled for neoadjuvant radiotherapy between 2011 and 2017 were enrolled in this study. SII values (SII = platelet × neutrophil/lymphocyte), prognostic nutritional index values (PNI = albumin concentration (g/L) + 5 × total lymphocyte count (109/L)), platelet–lymphocyte ratio (PLR), and neutrophil–lymphocyte ratio (NLR) were retrospectively collected and calculated before treatment. The Cut-off Finder application was applied to find out the cut-off points of the SII, NLR, PNI and PLR. A regression model was used to examine prognostic factors for overall survival (OS) rates.Results: The median follow-up was 44 months (3 to 83). Sixty patients (73.17%) underwent surgery as scheduled. This study found that factors improving OS were a lower SII (≤ 916.6 × 109/L) (P=0.040) and neoadjuvant chemoradiotherapy (NCRT) (P=0.034). The patients with a lower SII and NCRT had a better OS (P< 0.001). Moreover, additionally, a higher SII was associated with a lower resectability rate (P=0.035).Conclusion: The SII can predict resectability in ESCC patients following neoadjuvant radiotherapy. Both the SII and neoadjuvant chemoradiotherapy appear to influence OS.Keywords: ESCC, NCRT, SII, resectable

Weimin Cai,1 Xiao Wu,1 Yongxian Chen,2 Junkai Chen,3 Xinran Lin1 1Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2Department of Respiratory, Xiamen Second hospital, Xiamen, People’s Republic of China; 3Department of Emergency, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, People’s Republic of ChinaCorrespondence: Xinran Lin, Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China, Tel +86 18857838243, Email lxr190910@163.comObjective: This study aimed to identify the risk factors and construct a reliable prediction model of 28-day all-cause mortality in critically ill patients with acute pancreatitis (AP) using machine learning techniques.Methods: A total of 534 patients from three different institutions were included. Thirty-eight possible variables were collected from the Intensive care unit (ICU) admission for investigation. Patients were split into a training cohort (n = 400) and test cohort (n = 134) according to their source of hospital. The synthetic minority oversampling technique (SMOTE) was introduced to handle the inherent class imbalance. Six machine learning algorithms were applied in this study. The optimal machine learning model was chosen after patients in the test cohort were selected to validate the models. SHapley Additive exPlanation (SHAP) analysis was performed to rank the importance of variable. The predictive performance of the models was evaluated by the calibration curve, area under the receiver operating characteristics curves (AUROC), and decision clinical analysis.Results: About 13.5% (72/534) of all patients eventually died of all-cause within 28 days of ICU admission. Eight important variables were screened out, including white blood cell count, platelets, body temperature, age, blood urea nitrogen, red blood cell distribution width, SpO2, and hemoglobin. The support vector machine (SVM) algorithm performed best in predicting 28-d all-cause death. Its AUROC reached 0.877 (95% CI: 0.809 to 0.927, p < 0.001), the Youden index was 0.634 (95% CI: 0.459 to 0.717). Based on the risk stratification system, the difference between the high-risk and low-risk groups was significantly different.Conclusion: In conclusion, this study developed and validated SVM model, which better predicted 28-d all-cause mortality in critically ill patients with AP. In the future, we will continue to include patients from more institutions to conduct validation in different contexts and countries.Keywords: all-cause mortality, machine learning, acute pancreatitis, prognosis, predict

Xiaojun Chen,1,&ast; Shushu Zuo,1,&ast; Chunhua Zhang,1 Bing Sun,1 Mengyue Zhang,1 Dandan Jiang,2 Yanyan Chen2 1School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 2National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanyan Chen; Dandan Jiang, National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, No. 270, Xueyuan West Road, Lucheng District, Wenzhou, Zhejiang, 325027, People’s Republic of China, Tel +86 13858855689 ; +86 13506649289, Email cyy@eye.ac.cn; jiangdandan@eye.ac.cnObjective: This study aims to explore the effects of eye exercises on the accommodative ability of Chinese school-aged children.Methods: This study used a convenience cluster sampling and selected 149 students from grades 2– 5 in a Wenzhou primary school to participate in the intervention in June 2022. This study involved a one-month intervention teaching eye exercises using a composite feedback model. Assessments were made at 3 and 9 months post-intervention. Data collection occurred thrice, including a baseline and two follow-ups, measuring monocular and binocular accommodative facility, monocular and binocular accommodative amplitude, CISS scale, spherical equivalent refraction, and uncorrected visual acuity. Analysis used chi-square tests and generalized estimating equations to evaluate the exercises’ effectiveness, with a significance threshold of P < 0.05.Results: 134 students completed the follow-up, including 61 females (45.52%). After teaching intervention, students showed significant improvements in the accuracy of manipulation, rhythm, acupoint location, strength effectiveness and rhythm of acupressure eye exercises (all P < 0.05), with increases of 10.37%, 13.03%, 16.96%, and 25.17%, respectively. Follow-up assessments revealed both monocular and binocular accommodative amplitude at T3 were significantly higher than at T1 and T2. Moreover, the binocular accommodative amplitude in the high-quality eye exercise group remained significantly higher than that in the low-quality group even(B=1.39,1.46, P < 0.01). Eye exercises could improve monocular and binocular accommodative amplitude in the short term(P < 0.05). High-quality eye exercises could alleviate visual fatigue (B=− 2.00--3.49, both P < 0.05). However, eye exercises did not demonstrate any advantages in affecting spherical equivalent refraction or uncorrected visual acuity (P > 0.05).Conclusion: Eye exercises can alleviate myopia-related symptoms in Chinese children aged 7 to 11 years. However, this study did not find that eye exercises effectively reduce the degree of myopia in children.Trial Registration: The original trial (Registration site: https://www.chictr.org.cn/ Registration number: ChiCTR2300070903) was retrospectively registered on 26/04/2023.Keywords: Eye exercises, myopia, accommodative facility, accommodative amplitude, visual fatigue

Honggang Guo,1,&ast; Yabin Cui,2,&ast; Yanliang Bai,1 Fan Yan,1 Wenhui Zhang,1 Yuqing Chen,1,&ast; Mingyue Shi1,&ast; 1Department of Hematology, Zhengzhou University People’s Hospital and Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Hematology, Henan University People’s Hospital, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuqing Chen; Mingyue Shi, Department of Hematology, Zhengzhou University People’s Hospital and Henan Provincial People’s Hospital, &num;7 Weiwu Road, Zhengzhou, Henan, 450003, People’s Republic of China, Tel +86-18697321863 ; +86-17839931733, Email henanblood@sina.com; shimingyue16@gmail.comBackground: Relapsed/refractory acute myeloid leukemia (R/R-AML) has dismal prognosis due to chemotherapy resistance. Circular RNAs (circRNAs) have shown emerging roles in chemotherapy resistance in various cancers including hematologic malignancies. However, the potential roles of circRNAs in AML progression and drug resistance remain largely undetermined.Methods: In this study, circulating circRNAs expression profiles were analyzed among R/R-AML, de novo AML and healthy controls (HC) using a human circRNA Array. Bioinformatic analysis was carried out to explore the differentially expressed circRNAs (DE-circRNAs). GO, KEGG pathway analysis, along with circRNA-miRNA-mRNA network analysis, were conducted to identify the potential biological pathways involved in R/R-AML. Finally, the UALCAN database was used to assess the prognosis of different target DE-circRNAs-related mRNAs.Results: Forty-eight DE-circRNAs were upregulated, whereas twenty-seven DE-circRNAs were downregulated in R/R-AML samples. Up-regulated DE-circRNAs in R/R-AML samples were mainly enrichment in the biological processes and pathways of cell migration, microRNAs in cancers, Rap1 and Ras signaling pathways. Six DE-circRNAs were randomly selected to further explore their relationships with R/R-AML. GO and KEGG pathway analyses of the six candidate DE-circRNAs-related target mRNAs were mainly involved in the regulation of signal transduction and Ras signaling pathway. By overlapping our RNA-sequencing results of differentially expressed genes (DEGs) in R/R-AML samples with the candidate DE-circRNAs-predicted target mRNAs, we identified sixty-eight overlapping targeted mRNAs. Using UALCAN database analysis, we identified that AML patients with six upregulated DE-circRNA-related genes (ECE1, PI4K2A, SLC9A6, CCND3, PPP1R16B, and TRIM32) and one downregulated gene DE-circRNA-related genes (ARHGAP10) might have a poor prognosis.Conclusion: This study revealed the overall alterations of circRNAs in R/R-AML. DE-circRNAs and their related genes might be used as potential early, sensitive and stable biomarkers for AML diagnosis, R/R-AML monitoring, and even as novel treatment targets for R/R-AML.Keywords: Relapsed/refractory, acute myeloid leukemia, circular RNAs, biomarkers, prognosis

Xinfu Cao,1 Yi Sun,1 Yuqiao Chen,1 Chao Tang,2 Hongwen Yu,3 Xiaolong Li,1 Zhenhua Gu1 1Department of Cardiology, Changzhou Affiliated Hospital of Nanjing University of Chinese Medicine, Changzhou, Jiangsu Province, People’s Republic of China; 2Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, People’s Republic of China; 3Department of Cardiology, Gaochun Branch of Nanjing Hospital of Traditional Chinese Medicine, Nanjing City, Jiangsu Province, People’s Republic of ChinaCorrespondence: Zhenhua Gu; Xiaolong Li, Department of Cardiology, Changzhou Affiliated Hospital of Nanjing University of Chinese Medicine, Changzhou City, Jiangsu Province, People’s Republic of China, Email 18101490727@163.com; 15650796727@163.comObjective: To explore the risk factors of atrial fibrillation (AF) in patients with coronary heart disease (CHD), and to construct a risk prediction model.Methods: The participants in this case-control study were from the cardiovascular Department of Changzhou Affiliated Hospital of Nanjing University of Chinese Medicine from June 2016 to June 2023, and they were divided into AF group and non-AF group according to whether AF occurred during hospitalization. The clinical data of the two groups were compared by retrospective analysis. Multivariate Logistic regression analysis was used to investigate the risk factors of AF occurrence in CHD patients. The nomogram model was constructed with R 4.2.6 language “rms” package, and the model’s differentiation, calibration and effectiveness were evaluated by drawing ROC curve, calibration curve and decision curve.Results: A total of 1258 patients with CHD were included, and they were divided into AF group (n=92) and non-AF group (n=1166) according to whether AF was complicated. Logistic regression analysis showed that age, coronary multiple branch lesion, history of heart failure, history of drinking, pulmonary hypertension, left atrial diameter, left ventricular end-diastolic diameter and diabetes mellitus were independent risk factors for the occurrence of AF in CHD patients (P < 0.05). The ROC curve showed that the AUC of this model was 0.956 (95% CI (0.916, 0.995)) and the consistency index was 0.966. The calibration curve of the model is close to the ideal curve. The analysis of decision curve shows that the prediction value of the model is better when the probability threshold of the model is 0.042~0.963.Conclusion: The nomogram model established in this study for predicting the risk of AF in patients with CHD has better predictive performance and has certain reference value for clinical identification of high-risk groups prone to AF in patients with CHD.keywords: coronary heart disease, atrial fibrillation, risk factors, logistic regression analysis, nomogram model

Haijie Tan,1,&ast; Yi Chen,2,&ast; Yan Jiang,1 Xiaojing Sun,1 Wei Ye,1 Xuefang Zhu,1 Xiangsheng Xiong1 1Department of Anesthesiology, The Fifth People’s Hospital of Huaian, Huaian, People’s Republic of China; 2Department of Anesthesiology and Perioperative Medicine, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangsheng Xiong, Department of Anesthesiology, The Fifth People’s Hospital of Huaian, Huaian, People’s Republic of China, Email 158193942@qq.comBackground: Vasopressors remain an important strategy for managing spinal anesthesia-induced hypotension in women with preeclampsia. The aim of this study was to investigate the ED90s and efficacy ratio of phenylephrine and norepinephrine in managing spinal anesthesia-induced hypotension in women with preeclampsia during cesarean delivery.Methods: 60 women with preeclampsia, who underwent cesarean delivery, were randomly assigned to receive either a continuous intravenous infusion of phenylephrine or norepinephrine following spinal anesthesia. The initial dosage of phenylephrine or norepinephrine for the first women was 0.5 or 0.05 μg/kg/min, respectively, and subsequent infusion dosages were adjusted based on their efficacy in preventing spinal anesthesia-induced hypotension (defined as a systolic blood pressure less than 80% of the baseline level). The incremental or decremental doses of phenylephrine or norepinephrine were set at 0.1 or 0.01 μg/kg/min. The primary outcomes were the ED90s and efficacy ratio of phenylephrine and norepinephrine infusions for preventing spinal anesthesia-induced hypotension prior to delivery.Results: The results obtained from isotonic regression analysis revealed that the ED90 values of the phenylephrine and norepinephrine group for preventing spinal anesthesia-induced hypotension were 0.597 (95% CI: 0.582– 0.628) and 0.054 (95% CI: 0.053– 0.056) μg/kg/min, respectively, with an efficacy ratio of 11.1:1. The results of Probit regression analysis revealed that the ED90 values were determined to be 0.665 (95% CI: 0.576– 1.226) and 0.055 (95% CI: 0.047– 0.109) μg/kg/min, respectively, with an efficacy ratio of 12.1:1.Conclusion: The administration of 0.6 μg/kg/min phenylephrine and 0.05 μg/kg/min norepinephrine has been found to effectively manage a 90% incidence of spinal anesthesia-induced hypotension in women with preeclampsia.Keywords: ED90, phenylephrine, norepinephrine, spinal anesthesia-induced hypotension, preeclampsia, cesarean delivery

Lin Shen,1,&ast; Zixuan Chen,1,&ast; Zhi Zhang,2,&ast; Yunjiang Wu,3 Yue Ren,1 Ying Li,1 Yue Li,1 Xudong Yin,1 Fang Han,1 Yong Chen1 1Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou City, Jiangsu Province, People’s Republic of China; 2Department of Medical Oncology, Baoying Clinical College, Medical College of Yangzhou University, Yangzhou City, Jiangsu Province, People’s Republic of China; 3Department of Thoracic Surgery, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou City, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Chen, Department of Radio-Chemotherapy, Affiliated Hospital of Yangzhou University, Yangzhou University, Hanjiang Middle Road No. 368, Yangzhou, Jiangsu, 225009, People’s Republic of China, Tel +86-18051062926, Email chenyong_jsyz@sina.comPurpose: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line standard treatment for locally advanced or metastatic esophageal squamous cell carcinoma (ESCC). The evidence also demonstrates improved synergistic effects of chemotherapy when combined with delayed administration of ICIs. In this study, we conducted a retrospective investigation into the treatment efficacy of taxol plus platinum (TP) chemotherapy combined with delayed administration of PD-1 inhibitors for ESCC patients.Patients and Methods: Clinical data of ESCC patients who received PD-1 inhibitors 3– 5 days after TP chemotherapy as first-line treatment was retrospectively reviewed between January 2019 and April 2023. Clinical outcomes and treatment safety were analyzed. The potential roles of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV) were investigated.Results: A total of 34 locally advanced, recurrent or metastatic ESCC patients received PD-1 inhibitors 3– 5 days following TP chemotherapy were included. The objective response rate (ORR) and disease control rate (DCR) were 85.3% and 97.1% respectively. The median progression-free survival (PFS) and overall survival (OS) were 13.2 and 19.1 month respectively. Seven patients received radical surgery, 1 patient achieved pathologic complete response (pCR) and 3 patients achieved major pathologic response (MPR). Among the 27 patients without surgery, the median PFS and OS were 9.7 and 19.1 month respectively. A more favorable prognosis was correlated with NLR less than 3 at the 3rd and 4th cycle of immunochemotherapy. No significant correlations between other parameters (PLR, MLR and PIV) and prognosis were observed. A total of 22 patients developed grade 3– 4 toxicity events.Conclusion: The optimized sequence of PD-1 inhibitors administered 3– 5 days after TP chemotherapy as the first-line treatment of ESCC demonstrated favorable treatment efficacy. Pretreatment NLR of less than 3 at the 3rd and 4th cycle of immunochemotherapy is associated with a better prognosis.Keywords: immune checkpoint inhibitors, chemotherapy, rational sequence, esophageal squamous cell carcinoma, peripheral blood parameters

Yan Chen,1 Jiahuan Tong,2 Jianfeng Wang2 1Department of General Practice, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310018, People’s Republic of China; 2Department of Respiratory Diseases, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310018, People’s Republic of ChinaCorrespondence: Jianfeng Wang, Department of Respiratory Diseases, the First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Shangcheng District, Hangzhou, 310018, People’s Republic of China, Email 2001m@163.comAbstract: The clinical severity of Chlamydia psittaci infection ranges from asymptomatic to severe pneumonia. Diagnosis poses challenges due to its similarity to other respiratory infections. Treatment includes tetracyclines, macrolides, and fluoroquinolones, with limited evidence on the efficacy of omadacycline. We report a case of an 86-year-old male with severe psittacosis treated with omadacycline, resulting in significant improvement. This highlights the necessity for further research on omadacycline’s role in psittacosis treatment.Keywords: Chlamydia psittaci, omadacycline, pneumonia