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Chunrong Zuo,1,2 Nor Shafrin Ahmad,2 Lyu Zeng,1 Xiaogang Zhou,3 Feifei Li,2,4 Wuman Hong,2 Ping Gao1 1School of Education, Huainan Normal University, Anhui, 232038, People’s Republic of China; 2School of Educational Studies, Universiti Sains Malaysia, Gelugor, Penang, 11800, Malaysia; 3College of Physical Education and Health Science, Zhejiang Normal University, Jinhua, 321000, People’s Republic of China; 4Department of Art, Shandong Agricultural University, Shandong, 271000, People’s Republic of ChinaCorrespondence: Nor Shafrin Ahmad, School of Educational Studies, Universiti Sains Malaysia, Gelugor, Penang, 11800, Malaysia, Tel +60 465 325 69, Email sham@usm.my Xiaogang Zhou, College of Physical Education and Health Science, Zhejiang Normal University, Jinhua, 321000, People’s Republic of China, Tel +86 183 2904 0923, Email brucechou123456@gmail.comBackground and Objective: The mental health of economically disadvantaged college students in China is notably inferior to that of their non-disadvantaged peers. As such, these students necessitate a broader spectrum of psychological support beyond mere financial assistance. Seligman’s PERMA theory has established a compelling association between social support and positive emotions with subjective well-being. However, there is a scarcity of research focusing on character strengths within this framework, particularly the mechanisms that underlie their relationship. Hence, this study aims to examine the relationship between character strengths and subjective well-being among Chinese impoverished college students, while also delving into the chain mediating roles of perceived social support and positive emotions.Methods: A convenience sampling method was employed to collect cross-sectional data from impoverished college students. Participants (N=336, Mean age=20.67) were assessed using four instruments: the Chinese Virtues Questionnaire (CVQ-96), the Perceived Social Support Scale (PSSS), the Positive and Negative Affect Scale (PANAS), and the Satisfaction with Life Scale (SWLS).Results: Character strengths, perceived social support, positive emotions, and subjective well-being were all significantly positively correlated with each other (p< 0.01). In addition, regression analysis indicated that character strengths positively predicted perceived social support (β=0.71, p< 0.001), positive emotions (β=0.44, p< 0.001), and subjective well-being (β=0.52, p< 0.001). Perceived social support positively predicted positive emotions (β=0.34, p< 0.001), and subjective well-being (β=0.44, p< 0.001). Positive emotions positively predicted subjective well-being (β=0.88, p< 0.001). Furthermore, chain mediation analysis revealed that character strengths influenced subjective well-being both directly and indirectly through perceived social support and positive emotions.Conclusion: Perceived social support and positive emotions play a chain mediating role between character strengths and subjective well-being among impoverished college students.Keywords: character strengths, perceived social support, positive emotions, subjective well-being, Chinese, impoverished college students

Ran Zhao,1,&ast; Dexiang Ji,1,&ast; Yulan Zhou,1,2 Ling Qi,1,2 Fei Li1,2 1Jiangxi Provincial Key Laboratory of Hematological Diseases, Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Jiangxi Clinical Research Center for Hematologic Disease, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Li, Email yx021021@sina.comBackground: Immunosuppressive therapy (IST) with horse or rabbit anti-human thymocyte immunoglobulin (h-/r-ATG) and hematopoietic stem cell transplantation (HSCT) are two baseline treatments for severe aplastic anemia (SAA) and transfusion-dependent non-severe aplastic anemia (TD-NSAA) patients. Addition of thrombopoietin receptor agonists (TPO-RAs) to standard IST therapy (h-/r-ATG) has greatly improved the survival of SAA, whereas porcine anti-lymphocyte globulin (p-ALG) combined with TPO-RAs still had a matter of debate.Methods: We retrospectively compared the data of 48 AA patients in our center between 2020 and 2022, 23 AA patients received with p-ALG ± TPO-RAs, 25 AA patients underwent matched sibling donor (MSD-) or haploidentical (haplo-) HSCT.Results: For patients in the HSCT group, the ORR was 90.9% which was significantly higher than that in the IST±TPO-RAs group (45.5%, P = 0.001) at 3 months; moreover, patients who underwent HSCT achieved faster transfusion independence, better CR rate, shorter time of recovery normal blood routine, and the percentage of normal blood routine (all P < 0.05) compared with IST±TPO-RAs group. However, the ORR were similary at 6 months in the two groups (95.5% vs 81.8% P = 0.342), with a median follow up of 19.8 months (range, 0.3– 38.2 months), the 2-year FFS and OS in the two cohorts has no different. Subgroup analysis further indicated that the 2-year FFS and OS were similar between IST+TPO-RAs and haplo-HSCT subgroups, as well as in IST+TPO-RAs and MSD-HSCT cohorts. Moreover, the first-time hospitalizations were much more expensive in the HSCT group than in the IST±TPO-RAs group (402 756 vs. 292 902 yuan, P = 0.002).Conclusion: P-ALG-based-IST±TPO-RAs is a good treatment option with similar FFS and OS compared to allo- HSCT for AA patients without the opportunity of HSCT.Keywords: porcine anti-human thymocyte immunoglobulin, thrombopoietin receptor agonist, hematopoietic stem cell transplantation, aplastic anemia

Xu Tian,1,&ast; Fangrong Liu,2,&ast; Feili Li,3 Yi Ren,4 Hongcai Shang5 1Chongqing Center for Evidence-Based Traditional Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400020, People’s Republic of China; 2Outpatient Department, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 3Department of Nursing, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400020, People’s Republic of China; 4Department of Classic Traditional Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400020, People’s Republic of China; 5Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 101121, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Ren, Department of Classic Traditional Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, No. 6 of 7th Branch of Panxi Road, Jiangbei District, Chongqing, People’s Republic of China, Tel/Fax +86 023 67776180, Email cqszyyrenyi@163.com Hongcai Shang, Dongzhimen Hospital, Beijing University of Chinese Medicine, No. 5 of Haiyuncang, Dongcheng District, Beijing, People’s Republic of China, Tel/Fax +86 010 84013276, Email yxtx880919@163.comPurpose: While the benefits of exercises for chronic obstructive pulmonary disease (COPD) are well-established, the relative effectiveness of different exercise types for stable COPD remains unclear. This network meta-analysis aims to investigate the comparative effects of aerobic exercise (AE), resistance training (RT), endurance training (ET), and high-intensity interval training (HIIT) in stable COPD.Methods: Electronic searches were performed in PubMed, Embase, and the Cochrane library to identify relevant randomized controlled trials (RCTs) investigating the effects of exercises on 6-minute walk test distance (6MWD), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC), and St. George’s Respiratory Questionnaire (SGRQ) score. Two authors screened the retrieved articles, extracted relevant data, and assessed the risk of bias. Network meta-analysis was conducted using Stata 14.0.Results: This study included a total of 19 studies involving 951 patients with stable COPD. HIIT emerged as the most favorable exercise type for enhancing 6MWD, with a probability of 82.9%. RT exhibited the greatest efficacy in reducing SGRQ scores, with probability of 49.8%. Notably, ET demonstrated superiority in improving FEV1 and FVC, with probabilities of being most effective at 78.1% and 42.0%, respectively.Conclusion: This study suggests that HIIT may be a viable intervention for improving exercise capacity in stable COPD patients, compared to AE, RR, and ET. RT may hold promise for improving quality of life, and ET may demonstrate superiority in improving pulmonary function. However, variation in response likely depends on patient characteristics, program parameters, and delivery context. Future research should explore the synergistic effects of combining RT with ET/HIIT, focusing on patient subgroups, optimal dosing, and settings, as current guidelines indicate this combination may offer the most significant benefits.Keywords: COPD, exercise, pulmonary function, quality of life, network meta-analysis

Fan Li,1,&ast; Chuan-Guo Chen,2,&ast; Jiao-Fei Wei,1,3 Jia-Wen Lin,4 Zi-Ang Dou,3,4 Jun Shen,1 Shu-Qin Li1,3,4 1Department of Breast Surgery, the First People’s Hospital of Lianyungang, The Affiliated Hospital of XuZhou Medical University, Lianyungang, Jiangsu, People’s Republic of China; 2Department of General Surgery, Nanjing Meishan Hospital, Nanjing, Jiangsu, People’s Republic of China; 3Department of Clinical Medicine, Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of China; 4Department of clinical medicine, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Shen; Shu-Qin Li, Department of Breast Surgery, the First People’s Hospital of Lianyungang, The Affiliated Hospital of XuZhou Medical University, No. 6 Zhenhua East Road, High-tech Square, Lianyungang, Jiangsu Province, 222002, People’s Republic of China, Tel +861896132532 ; +8618961325781, Email shenjun2257@126.com; shuqinlilsh@126.comObjective: In this study, we aimed to establish the role of regenerating islet-derived family member 4 (Reg IV) as an independent risk factor and prognostic predictor in patients with T2-3 stage breast cancer who exhibit a non-pathological complete response (non-pCR) following neoadjuvant chemotherapy (NACT). Additionally, we examined the potential correlation and interaction between Reg IV and epidermal growth factor receptor (EGFR).Methods: A total of 67 patients with T2-3 stage breast cancer exhibiting non-pCR after NACT between September 2019 and December 2021 were included in this study. The analysis involved Kaplan–Meier survival comparisons, pooled hazard ratios for risk quantification, Cox regression analysis to isolate the impact of Reg IV on prognosis, Riskplots for visualizing risk profiles, and SHAP analysis to assess the importance of variables in predicting outcomes.Results: The findings indicate that patients positive for Reg IV had a significantly poorer prognosis (HR: 2.62, 95% CI: 1.06– 6.47). Co-expression of Reg IV and EGFR was associated with the worst outcomes compared to patients negative for both markers. Cox regression analysis confirmed the independent prognostic impact of Reg IV (HR: 2.63, 95% CI: 1.66– 3.59). Riskplot analysis showed that patients positive for both Reg IV and EGFR predominantly experienced disease progression. SHAP analysis further reinforced the significant effect of Reg IV on the disease course, without substantial interaction with EGFR.Conclusion: Reg IV may serve as an independent risk factor and predictive marker for adverse outcomes in patients with T2-3 stage breast cancer who do not achieve non-pCR following NACT.Keywords: breast cancer, NACT, neoadjuvant chemotherapy, non-pCR, non-pathologic complete response, reg IV, risk factor

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

Jun Yan,1 Rongrong Zheng,1 Zhongdong Zhang,1 Jinchuan Shi,1 Tingbo Yan,2 Hong Liu,3 Feng Li1 1The Second Infectious Disease Department, Xixi Hospital of Hangzhou, Hangzhou, 310023, People’s Republic of China; 2Radiology Department, Xixi Hospital of Hangzhou, Hangzhou, 310023, People’s Republic of China; 3Pathology Department, Xixi Hospital of Hangzhou, Hangzhou, 310023, People’s Republic of ChinaCorrespondence: Feng Li, The Second Infectious Disease Department, Xixi Hospital of Hangzhou, No. 2 Hengbu Street, Liuxia Town, Xihu District, Hangzhou, 310023, People’s Republic of China, Email lfnice@foxmail.comBackground: Non-tuberculous mycobacteria (NTM) are a group of mycobacteria that are commonly found in the environment and can cause disease in humans. The symptoms of NTM infection can be similar to those of tuberculosis, making diagnosis challenging. The morbidity associated with NTM is increasing, and clinical management can be challenging.Case Description: This report details the case of a 32-year-old male who was found to have multiple enlarged and partially necrotic lymph nodes in the neck, axilla, mediastinum, and retroperitoneum. The causative agent was rapidly identified as Mycobacterium paracondontium through pathogen-targeted sequencing (tNGS). After two weeks of treatment with azithromycin, moxifloxacin, rifabutin, and amikacin, the patient’s uncomfortable symptoms had resolved, and he is currently undergoing further review.Conclusion: It is imperative that clinicians remain vigilant for the presence of NTM, particularly those that are rare, given their pervasiveness in the environment. Prompt diagnosis is of paramount importance, and molecular identification techniques represent a crucial tool in this regard. In vitro drug sensitivity testing should be conducted whenever feasible to guarantee the administration of an efficacious treatment regimen.Keywords: non-tuberculous mycobacteria, Mycobacterium paracondontium, lymph nodes, case report

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

Lili Liu,1,&ast; Feifei Li,2,3,&ast; Xinyu Gu,2,3 Runkai Jiao4,5 1School of Education, Changchun Normal University, Changchun, Jilin, People’s Republic of China; 2College of Education, Wenzhou University, Wenzhou, Zhejiang, People’s Republic of China; 3Center for Psychological and Behavioral Research, Wenzhou University, Wenzhou, Zhejiang, People’s Republic of China; 4School of Psychology, Northeast Normal University, Changchun, Jilin, People’s Republic of China; 5National Training Center for Kindergarten Principals, Ministry of Education, Changchun, Jilin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feifei Li, Wenzhou University, Chashan Higher Education Park, Wenzhou, Zhejiang Province, 325035, People’s Republic of China, Tel +8615143003119, Email 20220053@wzu.edu.cnPurpose: Possessing a calling to teach is a core and essential quality of good kindergarten teachers, and it is critical to explore which factors positively impact kindergarten teachers’ career calling. Developing a career calling is a meaning-making process that can be influenced by the actions of others in the workplace. During the frequent parent-teacher interactions, parent-initiated support may serve as significant interpersonal cues for kindergarten teachers in developing their career calling. Thus, the present study examined the effect of parent-initiated support on kindergarten teachers’ career calling. Further, we investigated the multiple mediating roles of global and specific basic psychological need satisfaction based on the self-determination theory (SDT).Methods: Cross-sectional data were collected from 629 kindergarten teachers in China and analyzed using Mplus 8.3 software and the Process 3.5 macro of SPSS 26.0 software. Before testing the hypothesis, we used Mplus 8.3 to save factor scores from the Bifactor model of basic psychological need satisfaction and two uni-dimensional models of parent-initiated support and career calling. Subsequently, using the Process 3.5 macro within SPSS 26.0 software, we conducted path analysis to examine the total and mediating effects between parent-initiated support and kindergarten teachers’ career calling.Results: The results revealed a positive effect of parent-initiated support on teachers’ career calling. Teachers’ global and specific competence need satisfaction partially mediated this positive effect, while the mediating effects of teachers’ specific autonomy and relatedness need satisfaction were non-significant.Conclusion: These findings suggest that parent-initiated support is an important job resource for kindergarten teachers’ development of career calling. In addition to satisfying global psychological needs, satisfying specific needs (eg, competence need) provides additional benefits to kindergarten teachers’ experience of career calling.Keywords: parent-initiated support, career calling, basic psychological need satisfaction, kindergarten teacher, self-determination theory

Siyu Pan,1 Yixiao Wang,1 Yuchen Zhang,1 Xiaoyu Ma,1 Jingfeng Peng,1 Fangfang Li,1,2 Wenhao Qian,1,2 Jing Zong1,2 1Institute of Cardiovascular Diseases, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Jing Zong, Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China, Tel +8618205000580, Email xyfyzongjing@126.comObjective: To investigate the Levels of Nucleotide-binding, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) and Adiponectin (APN) and their relationship with the severity of coronary artery disease in patients with Unstable Angina (UA) and Type 2 Diabetes (T2D).Methods: Two hundred and thirty-one patients with UA were diagnosed by CAG in the Department of Cardiology of the Affiliated Hospital of Xuzhou Medical University from July 2022 to May 2023 were included, and 74 healthy subjects were included as the control group. The levels of NLRP3 and APN in each group were detected by ELISA and the Gensini score in each patient according to the results of CAG. The correlations between NLRP3, APN, and Gensini score were analyzed. According to whether complicated with T2D or not, we further analyze the effect of NLRP3 and APN levels of patients with UA and T2D on the severity of coronary artery stenosis.Results: The levels of NLRP3 in UA with T2D group were the highest, followed by simple UA group, and the lowest in the control group, and the level of APN was the opposite. Spearman Correlation analysis showed that the level of NLRP3 was positively correlated with Gensini score (ρ1=0.688, P

Fengfeng Li,1 Yang Jia,1 Jun Fang,2 Linqiang Gong,3 Yazhou Zhang,4 Shanshan Wei,5 Linlin Wu,6 Pei Jiang5 1Neurosurgery Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China; 2Anesthesiology Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China; 3Gastroenterology Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China; 4Foot and Ankle Surgery Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China; 5Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Jining, Shandong, 272000, People’s Republic of China; 6Oncology Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of ChinaCorrespondence: Linlin Wu, Oncology Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China, Tel +86 632-5513457, Email linlinliff@163.com Pei Jiang, Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Jining, Shandong, 272000, People’s Republic of China, Tel +86 537-2106208, Email jiangpeicsu@sina.comBackground: Traumatic brain injury (TBI) is a condition characterized by structural and physiological disruptions in brain function caused by external forces. However, as the highly complex and heterogenous nature of TBI, effective treatments are currently lacking. Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) has shown notable antinociceptive and anti-inflammatory effects, yet its detailed neuroprotective effects and mode of action remain incompletely understood. This study investigated the neuroprotective effects and the underlying mechanisms of MOTS-c.Methods: Adult male C57BL/6 mice were randomly divided into three groups: control (CON) group, MOTS-c group and TBI group. Enzyme-linked immunosorbent assay (ELISA) kit method was used to measure the expression levels of MOTS-c in different groups. Behavioral tests were conducted to assess the effects of MOTS-c. Then, transcriptomics and metabolomics were performed to search Differentially Expressed Genes (DEGs) and Differentially Expressed Metabolites (DEMs), respectively. Moreover, the integrated transcriptomics and metabolomics analysis were employed using R packages and online Kyoto Encyclopedia of Genes and Genomes (KEGG) database.Results: ELISA kit method showed that TBI resulted in a decrease in the expression of MOTS-c. and peripheral administration of MOTS-c could enter the brain tissue after TBI. Behavioral tests revealed that MOTS-c improved memory, learning, and motor function impairments in TBI mice. Additionally, transcriptomic analysis screened 159 differentially expressed genes. Metabolomic analysis identified 491 metabolites with significant differences. Integrated analysis found 14 KEGG pathways, primarily related to metabolic pathways. Besides, several signaling pathways were enriched, including neuroactive ligand–receptor interaction and retrograde endocannabinoid signaling.Conclusion: TBI reduced the expression of MOTS-c. MOTS-c reduced inflammatory responses, molecular damage, and cell death by down-regulating macrophage migration inhibitory factor (MIF) expression and activating the retrograde endocannabinoid signaling pathway. In addition, MOTS-c alleviated the response to hypoxic stress and enhanced lipid β-oxidation to provide energy for the body following TBI. Overall, our study offered new insights into the neuroprotective mechanisms of MOTS-c in TBI mice.Keywords: MOTS-c, TBI, transcriptomics, metabolomics, neuroprotective

Xin Liu,1,&ast; Ruofan Xi,1,&ast; Xinran Du,1 Yi Wang,1 Linyan Cheng,1 Ge Yan,1 Hanzhi Lu,1 Te Liu,2 Fulun Li1 1Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Te Liu; Fulun Li, Email liute1979@shutcm.edu.cn; drlifulun@163.comBackground: Psoriasis is a common chronic inflammatory skin condition. The emergence of psoriasis has been linked to dysbiosis of the microbiota on the skin surface and an imbalance in the immunological microenvironment. In this study, we investigated the therapeutic impact of topical thymopentin (TP5) on imiquimod (IMQ)-induced psoriasis in mice, as well as the modulatory influence of TP5 on the skin immune milieu and the skin surface microbiota.Methods: The IMQ-induced psoriasis-like lesion mouse model was used to identify the targets and molecular mechanisms of TP5. Immunofluorescence was employed to identify differences in T-cell subset expression before and after TP5 therapy. Changes in the expression of NF-κB signaling pathway components were assessed using Western blotting (WB). 16S rRNA sequencing and network pharmacology were used to detect changes in the skin flora before and after TP5 administration.Results: In vivo, TP5 reduced IMQ-induced back inflammation in mice. H&E staining revealed decreased epidermal thickness and inflammatory cell infiltration with TP5. Masson staining revealed decreased epidermal and dermal collagen infiltration after TP5 administration. Immunohistochemistry showed that TP5 treatment dramatically reduced IL-17 expression. Results of the immunoinfiltration analyses showed psoriatic lesions with more T-cell subsets. According to the immunofluorescence results, TP5 dramatically declined the proportions of CD4+, Th17, ROR+, and CD8+ T cells. WB revealed that TP5 reduced NF-κB pathway expression in skin tissues from IMQ-induced psoriasis model mice. 16S rRNA sequencing revealed a significant increase in Burkholderia and Pseudomonadaceae_Pseudomonas and a significant decrease in Staphylococcaceae_Staphylococcus, Aquabacterium, Herbaspirillum, and Balneimonas. Firmicutes dominated the skin microbial diversity after TP5 treatment, while Bacteroidetes, Verrucomicrobia, TM7, Proteobacteria, Actinobacteria, Acidobacteria, Gemmatimonadetes, and other species dominated in the IMQ group.Conclusion: TP5 may treat psoriasis by modulating the epidermal flora, reducing NF-κB pathway expression, and influencing T-cell subsets.Keywords: psoriasis, thymopentin, 16S rRNA sequencing, T-cell subsets

Shixin Ma,1,2 Fei Li,2 Lunqing Wang2 1Graduate School, Dalian Medical University, Dalian, Liaoning, 116000, People’s Republic of China; 2Department of Thoracic Surgery, Qingdao Municipal Hospital, Qingdao, Shandong, 266071, People’s Republic of ChinaCorrespondence: Lunqing Wang, Department of Thoracic Surgery, Qingdao Municipal Hospital, No. 5 Donghai Middle Road, Qingdao, People’s Republic of China, Tel +86 532 87077952, Email wanglunqing1973@163.comPurpose: The purpose of this study was to investigate the predictive value of Pan-Immune-Inflammation Value (PIV) combined with the PILE score for immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) and to construct a nomogram prediction model to provide reference for clinical work.Patients and Methods: Patients with advanced NSCLC who received ICIs treatment in Qingdao Municipal Hospital from January 2019 to December 2021 were selected as the study subjects. The chi-square test, Kaplan-Meier survival analysis, and Cox proportional risk regression analysis were used to evaluate the prognosis. The results were visualized by a nomogram, and the performance of the model was judged by indicators such as the area under the subject operating characteristic curve (AUC) and C-index. The patients were divided into high- and low-risk groups by PILE score, and the prognosis of patients in different risk groups was evaluated.Results: Multivariate Cox regression analysis showed that immune-related adverse events (irAEs) were prognostic factors for overall survival (OS) improvement, and ECOG PS score ≥ 2, bone metastases before treatment, and high PIV expression were independent risk factors for OS. The C index of OS predicted by the nomogram model is 0.750 (95% CI: 0.677– 0.823), and the Calibration and ROC curves show that the model has good prediction performance. Compared with the low-risk group, patients in the high-risk group of PILE were associated with a higher inflammatory state and poorer physical condition, which often resulted in a poorer prognosis.Conclusion: PIV can be used as a prognostic indicator for patients with advanced NSCLC treated with ICIs, and a nomogram prediction model can be constructed to evaluate the survival prediction of patients, thus contributing to better clinical decision-making and prognosis assessment.Keywords: non-small cell lung cancer, immune checkpoint inhibitors, pan-immune-inflammation value, prognosis, nomogram

Haotian Zhou,1,2,&ast; Yaji Yang,1,2,&ast; Yanhao Zhang,3 Feilong Li,1,2 Yidong Shen,4 Leilei Qin,1,2 Wei Huang1,2 1Department of Orthopaedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Orthopedic Laboratory of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3College of Pharmacy, Army Military Medical University, Chongqing, 400038, People’s Republic of China; 4Department of Orthopaedics, The First People’s Hospital of Yancheng, Yancheng, 224000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leilei Qin; Wei Huang, Email 253505921@qq.com; huangwei68@263.netAbstract: Periprosthetic joint infection (PJI) is a catastrophic complication following joint replacement surgery, posing significant challenges to orthopedic surgeons. Due to the lack of a definitive diagnostic gold standard, timely treatment initiation is problematic, resulting in substantial economic burdens on patients and society. In this review, we thoroughly analyze the complexities of PJI and emphasize the importance of accurate diagnosis and effective treatment. The article specifically focuses on the advancements in diagnostic techniques, ranging from traditional pathogen culture to advanced molecular diagnostics, and discusses their role in enhancing diagnostic accuracy. Additionally, we review the latest surgical management strategies, including everything from debridement to revision surgeries. Our summary aims to provide practical information for the diagnosis and treatment of PJI and encourages further research to improve diagnostic accuracy and treatment outcomes.Keywords: arthroplasty, periprosthetic joint infection, PJI, molecular diagnosis, pathogenesis diagnosis, antibiotic application, recurrence of infection

Yuelin Zhang, Xue Lin, Xinxin Chen, Weixiang Fang, Kailing Yu, Wenting Gu, Yinghui Wei, Hangsheng Zheng, Jigang Piao, Fanzhu Li School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of ChinaCorrespondence: Fanzhu Li; Ji-Gang Piao, Email lifanzhu@zcmu.edu.cn; jgpiao@zcmu.edu.cnAbstract: Mesoporous silica nanoparticles (MSNs) have attracted extensive attention as drug delivery systems because of their unique meso-structural features (high specific surface area, large pore volume, and tunable pore structure), easily modified surface, high drug-loading capacity, and sustained-release profiles. However, the enduring and non-specific enrichment of MSNs in healthy tissues may lead to toxicity due to their slow degradability and hinder their clinical application. The emergence of degradable MSNs provided a solution to this problem. The understanding of strategies to regulate degradation and clearance of these MSNs for promoting clinical trials and expanding their biological applications is essential. Here, a diverse variety of degradable MSNs regarding considerations of physiochemical properties and doping strategies of degradation, the biodistribution of MSNs in vivo, internal clearance mechanism, and adjusting physical parameters of clearance are highlighted. Finally, an overview of these degradable and clearable MSNs strategies for biosafety is provided along with an outlook of the encountered challenges. Keywords: mesoporous silica nanoparticles, degradation, clearance, biodistribution, strategies

Dan Qi,1– 9 Xi Zhang,1– 8 Fangli Li,10 Shengrui Zhao,2– 8 Qiumin Wang,1– 8 Wen Liu,2– 8 Lei Yan,1– 8 Yanbo Du1– 8 1State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, People’s Republic of China; 2National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, People’s Republic of China; 3Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, People’s Republic of China; 4Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, People’s Republic of China; 5Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, People’s Republic of China; 6Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 7Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No. 2021RU001), Jinan, Shandong, People’s Republic of China; 8Medical Integration and Practice Center, Shandong University, Jinan, Shandong, People’s Republic of China; 9Weifang People’s Hospital, Weifang, Shandong, People’s Republic of China; 10Department of Gynecology and Obstetrics, Public Health Clinical Center Affiliated to Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Yanbo Du, Center for Reproductive Medicine, Shandong University, Jinan, 250012, Shandong, People’s Republic of China, Tel +86 1 301 173 4515, Email duyanboivf@163.comPurpose: The objective of this study was to assess reproductive outcomes of D6 blastocysts transferred on day 6 in comparison to those transferred on day 7 of progesterone exposure in frozen-thawed embryo transfer cycles.Patients and Methods: This retrospective cohort study included 2029 D6 single blastocysts from the first frozen-thawed embryo transfer cycles of patients at the Hospital for Reproductive Medicine Affiliated to Shandong University from February 2017 to January 2020. Participants were divided into Group A (blastocyst transferred on the 6th day of progesterone exposure, n=1634) and Group B (blastocyst transferred on the 7th day of progesterone exposure, n=395).Results: The live birth rate was comparable between Group A and Group B (38.7% versus 38.7%, P=0.999). Subgroup analysis revealed a significantly higher preterm birth rate in D6 single blastocysts transferred on the 7th day than in those transferred on the 6th day of progesterone exposure for natural cycle frozen-thawed embryo transfer (5.2% versus 11.3%, P=0.020). After adjustment for potential confounders, the differences in the preterm birth rate in natural cycles persisted (adjusted odds ratio 2.347, 95% confidence interval 1.129– 4.877, P=0.022).Conclusion: In frozen-thawed embryo transfer cycles, transferring on the 6th or 7th day of progesterone exposure of D6 blastocysts did not affect the live birth rate; however, when a natural cycle protocol is adopted, the possible preterm risk of transferring D6 blastocysts on the 7th day of progesterone exposure should be noted.Keywords: frozen-thawed embryo transfer, blastocyst transfer, endometrium preparation, live birth rate

You Zhang,1,&ast; Chi Geng,1,&ast; Yulun Zhou,1,&ast; Feng Li,1 Siliang Peng,1 Xinru Guo,1 Xiaosong Gu,1 Jing Li,2 Hui Li1 1Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, People’s Republic of China; 2Department of Intensive Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Li, Department of Cardiology, The Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Suzhou, 215006, People’s Republic of China, Email 9911263@163.com Jing Li, Department of Intensive Care Medicine, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, 215006, People’s Republic of China, Email 18862130763@163.comBackground: Vascular adhesion protein-1 (VAP-1), an inflammation-inducible endothelial cell molecule, was reported to be implicated in a variety of cardiovascular diseases. However, the clinical significance of circulating VAP-1 levels in patients with coronary heart disease (CHD) remains less studied.Patients and Methods: We retrospectively analyzed clinical data of 336 hospitalized patients in the Second Affiliated Hospital of Soochow University from May 2020 to September 2022, 174 of which were diagnosed with CHD. Serum VAP-1 was measured by enzyme-linked immunosorbent assay at enrollment. The primary end point of this study was the occurrence of major adverse cardiovascular events (MACE). The coronary stenosis and clinical manifestations of CHD were assessed and recorded from medical records or follow-up calls. The relevant results were obtained, and the reliability of the conclusions was verified through regression analysis, curve fitting, and survival curve.Results: After adjusting for potential confounders, higher serum VAP-1 level was associated with increased risk of MACE in patients with CHD [(HR = 5.11, 95% CI = 1.02– 25.59), (HR = 5.81, 95% CI = 1.16– 29.11)]. The results of curve fitting and survival analysis were consistent with those of regression analysis. However, no significant association was observed between VAP-1 and MACE in the entire study population [(HR = 5.11, 95% CI = 0.41– 1.93), (HR = 1.17, 95% CI = 0.52– 2.62)]. Furthermore, the level of VAP-1 did not show a significant correlation with coronary stenosis and the clinical manifestations of CHD.Conclusion: These findings suggested that CHD patients with higher serum levels of VAP-1 are at a higher risk of adverse cardiovascular outcomes.Keywords: vascular adhesion protein-1, atherosclerosis, coronary heart disease, major adverse cardiovascular events

Han Luo,1,&ast; Xiaofei Wang,1,&ast; Mengqi Fang,1 Huifan Yu,1 Lili Gui,1 Zhengkun Wu,1 Jianyong Sheng,2 Fei Li1 1Hubei Key Laboratory of Wudang Local Chinese Medicine Research, School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 2Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Li, Hubei University of Medicine, 30 Renmin South Road, Shiyan, Hubei, 442000, People’s Republic of China, Email piaopodexinlifei@163.comIntroduction: Although flavonoid compounds exhibit various pharmacological activities, their clinical applications are restricted by low oral bioavailability owing to their poor solubility. Nanocrystals (NCs) represent an excellent strategy for enhancing the oral bioavailability of flavonoids. Hydroxyethyl starch (HES), a biomaterial compound used as a plasma expander, could be an ideal stabilizer material for preparing flavonoid NCs.Methods: HES was used to stabilize flavonoid nanocrystals (NCs), using luteolin (LUT) as a model drug. After full characterization, the freeze-drying and storage stability, solubility, intestinal absorption, pharmacokinetics, and in vivo anti-hyperuricemic effect of the optimized HES-stabilized LUT NCs (LUT-HES NCs) were investigated.Results: Uniformed LUT-HES NCs were prepared with mean particle size of 191.1± 16.8 nm, zeta potential of about − 23 mV, drug encapsulation efficiency of 98.52 ± 1.01%, and drug loading of 49.26 ± 0.50%. The freeze-dried LUT-HES NCs powder showed good re-dispersibility and storage stability for 9 months. Notably, compared with the coarse drug, LUT-HES NCs exhibited improved saturation solubility (7.49 times), increased drug dissolution rate, enhanced Caco-2 cellular uptake (2.78 times) and oral bioavailability (Fr=355.7%). Pharmacodynamic studies showed that LUT-HES NCs remarkably lowered serum uric acid levels by 69.93% and ameliorated renal damage in hyperuricemic mice.Conclusion: HES is a potential stabilizer for poorly soluble flavonoid NCs and provides a promising strategy for the clinical application of these compounds. LUT-HES NCs may be an alternative or complementary strategy for hyperuricemia treatment.Keywords: Hydroxyethyl starch, nanocrystals, stabilizer, luteolin, oral bioavailability, anti-hyperuricemia

Deyi Huang,1 Xingan Yang,2 Hongbiao Ruan,3 Yushui Zhuo,1 Kai Yuan,4 Bowen Ruan,1 Fang Li1 1Department of Ultrasound, The People’s Hospital of Yuhuan, Yuhuan City, Zhejiang Province, People’s Republic of China; 2Department of Ultrasound, Taizhou Hospital of Zhejiang Province, Linhai City, Zhejiang Province, People’s Republic of China; 3Department of Cardiology, The People’s Hospital of Yuhuan, Yuhuan City, Zhejiang Province, People’s Republic of China; 4Department of Clinical Laboratory, The People’s Hospital of Yuhuan, Yuhuan City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Fang Li, Department of Ultrasound, The People’s Hospital of Yuhuan, No. 18, Changle Road, Yuhuan City, Zhejiang Province, 317600, People’s Republic of China, Tel +8613967672898, Email 3260772796@qq.comIntroduction: Chronic coronary artery disease (CAD) management often relies on myocardial contrast echocardiography (MCE), yet its effectiveness is limited by subjective interpretations and difficulty in distinguishing hibernating from necrotic myocardium. This study explores the integration of machine learning (ML) with radiomics to predict functional recovery in dyskinetic myocardial segments in CAD patients undergoing revascularization, aiming to overcome these limitations.Methods: This prospective study enrolled 55 chronic CAD patients, dividing into training (39 patients, 205 segments) and testing sets (16 patients, 68 segments). Dysfunctional myocardial segments were identified by initial wall motion scores (WMS) of ≥ 2 (hypokinesis or higher). Functional recovery was defined as a decrease of ≥ 1 grade in WMS during follow-up echocardiography. Radiomics features were extracted from dyssynergic segments in end-systolic phase MCE images across five cardiac cycles post- “flash” impulse and processed through a five-step feature selection. Four ML classifiers were trained and compared using these features and MCE parameters, to identify the optimal model for myocardial recovery prediction.Results: Functional improvement was noted in 139 out of 273 dyskinetic segments (50.9%) following revascularization. Receiver Operating Characteristic (ROC) analysis determined that myocardial blood flow (MBF) was the most precise clinical predictor of recovery, with an area under the curve (AUC) of 0.770. Approximately 1.34 million radiomics features were extracted, with nine features identified as key predictors of myocardial recovery. The random forest (RF) model, integrating MBF values and radiomics features, demonstrated superior predictive accuracy over other ML classifiers. Validation of the RF model on the testing dataset demonstrated its effectiveness, evidenced by an AUC of 0.821, along with consistent calibration and clinical utility.Conclusion: The integration of ML with radiomics from MCE effectively predicts myocardial recovery in CAD. The RF model, combining radiomics and MBF values, presents a non-invasive, precise approach, significantly enhancing CAD management.Keywords: coronary artery disease, myocardial contrast echocardiography, radiomics, machine learning, myocardial recovery prediction, random forest

Songtao Yang, Jie Cao, Ying Wang, Qi Chen, Fangyu Li, Yuanyuan Gao, Rui Li, Li Yuan Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of ChinaCorrespondence: Li Yuan, Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Email yuanli18cn@126.comBackground: The “gut-islets axis” is an important endocrine signaling axis that regulates islets function by modulating the gut microbiota and endocrine metabolism within the gut. However, the specific mechanisms and roles of the intestine in islets regulation remain unclear. Recent studies investigated that exosomes derived from gut microbiota can transport signals to remotely regulate islets β-cell function, suggesting the possibility of novel signaling pathways mediated by gut exosomes in the regulation of the “gut-islet axis.”.Methods: The exosomes were isolated from the intestinal enteroendocrine cell-line STC-1cells culture supernatants treated with palmitate acid (PA) or BSA. Metabolic stress models were established by separately subjecting MIN6 cells to PA stimulation and feeding mice with a high-fat diet. Intervention with exosomes in vitro and in vivo to assess the biological effects of exosomes on islets β cells under metabolic stress. The Mas receptor antagonist A779 and ACE2ko mice were used to evaluate the role of exosomal ACE2.Results: We found ACE2, a molecule that plays a crucial role in the regulation of islets function, is abundantly expressed in exosomes derived from STC-1 under physiological normal condition (NCEO). These exosomes cannot only be taken up by β-cells in vitro but also selectively transported to the islets in vivo. Following intervention with NCEXO, both Min6 cells in a lipotoxic environment and mice on a high-fat diet exhibited significant improvements in islets β-cell function and β-cell mass. Further investigations demonstrated that these protective effects are attributed to exosomal ACE2, as ACE2 inhibits NLRP3 inflammasome activation and reduces β-cell pyroptosis.Conclusion: ACE2-enriched exosomes from the gut can selectively target islets, subsequently inhibiting NLRP3 inflammasome activation and β cell pyroptosis, thereby restoring islets β cell function under metabolic stress. This study provides novel insights into therapeutic strategies for the prevention and treatment of obesity and diabetes.Keywords: exosomes, ACE2, islets β cell, the NLRP3 inflammasome

Chenxi Ouyang,1,2 Changjiang Meng,3 Fei Li,3 Shanshan Nie,3 Liying Gong,4 Yu Cao,5 Hong Yuan,3,5 Zeying Feng6 1School of Pharmacology, University of South China, Hengyang, Hunan, People’s Republic of China; 2The Affiliated Nanhua Hospital, Department of Pharmacy, Hengyang Medical School University of South China, Hengyang, Hunan, People’s Republic of China; 3Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 5Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 6Clinical Trial Institution Office, Liuzhou Hospital of Guangzhou Women and Children’s Medical Center, Liuzhou, Guangxi, People’s Republic of ChinaCorrespondence: Zeying Feng, Clinical Trial Institution Office, Liuzhou Hospital of Guangzhou Women and Children’s Medical Center, No. 50 Boyuan Avenue, Liuzhou, Guangxi, 545000, People’s Republic of China, Email fengzeying@foxmail.comPurpose: Mechanistic studies showed that morphine may impair the antiplatelet effect of P2Y12 inhibitors. However, Several clinical studies with cardiovascular events as an outcome are contradictory, and the broader impact of this drug interaction on additional organ systems remains uncertain. With multisource data, this study sought to determine the effects of morphine interaction with P2Y12 inhibitors on major adverse outcomes comprehensively, and identify the warning indicators.Patients and Methods: Interaction signals were sought in 187,919 safety reports from the FDA Adverse Event Reporting System (FAERS) database, utilizing reporting odds ratios (repOR). In a cohort of 5240 acute coronary syndrome patients, the analyses were validated, and the biological effects of warning indicators were further studied with Mendelian randomization and mediation analysis.Results: Potential risk of renal system adverse events in patients cotreated with morphine is significantly higher in FAERS (repOR 4.83, 95% CI 4.42– 5.28, false discovery rate adjusted-P =3.55&ast;10− 209). The analysis of in-house patient cohorts validated these results with an increased risk of acute kidney injury (adjusted OR: 1.65; 95% CI: 1.20 to 2.26), and we also found a risk of myocardial infarction in patients treated with morphine (adjusted OR: 1.55; 95% CI: 1.14 to 2.11). The Morphine group exhibited diminished Plateletcrit (PCT) levels post-surgery and lower PCT levels were associated with an increased risk of AKI.Conclusion: The administration of morphine in patients treated with P2Y12 receptor inhibitors should be carefully evaluated. PCT may serve as a potential warning indicator for morphine-related renal injury.Keywords: P2Y12 receptor inhibitors, morphine, kidney injury, Mendelian randomization

Fei Li,1,&ast; Feifei Yan,2,&ast; Shengnan Liu,1,&ast; Rewaan Baheti,1 Yujia Feng,1 Jing Wan1 1Department of Cardiovascular Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430000, People’s Republic of China; 2Cardiac Ultrasound Department, Zhongnan Hospital of Wuhan University, Wuhan, 430000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Wan, Department of Cardiology, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, Hubei Province, 430071, People’s Republic of China, Tel +86-027-67813477, Email wanjing_zn@163.comPurpose: In essential hypertensive patients, cardiac remodeling may be associated with the risk of renal damage in the future which can be reflected by the estimated glomerular filtration rate (eGFR). Through retrospective analysis, we evaluated the potential of cardiac remodeling based on echocardiographic measurements to predict the risk of renal damage in the future with hypertensive patients.Methods: We retrospectively analyzed the relationship between the changes of left heart structure and function and renal damage for 510 patients with hypertension, who were diagnosed between 2016 to 2022. Demography data, clinical data, blood samples and echocardiographic variables were used for survival analysis, and the Cox proportional hazards regression model was used.Results: In our study, we found that age, serum creatinine (SCR), creatine kinase isoenzyme MB (CK MB), abnormal high-sensitivity troponin I (TNI), interventricular septum thickness (IVST) and left ventricular ejection fraction (LVEF) could be used as independent predictors in risk of renal impairment in hypertensive patients (p< 0.05). Combined in a score where one point was given for the presence of each of the parameters above, this score could strongly predict renal function damage in the future (p< 0.05). In receiver operating characteristics (ROC) curve analyses, the area under the curve of the risk factor score was 0.849 (P< 0.001).Conclusion: In essential hypertensive patients, LVEF and IVST can predict the risk of future adverse renal outcomes. Moreover, combining risk variables into a simplified score may enable to assess the risk of renal impairment in hypertensive patients at an early stage.Keywords: hypertension, echocardiography, changes of cardiac structure and function, progression of renal damage, hypertensive nephropathy

Guang-Hong Xie,1,&ast; Jun Shen,2,&ast; Fan Li,2 Huan-Huan Yan,2 Ying Qian3 1Department of Operating Room, The First People’s Hospital of Lianyungang, The Affiliated Hospital of XuZhou Medical University, Lianyungang, Jiangsu, 222002, People’s Republic of China; 2Department of Breast Surgery, The First People’s Hospital of Lianyungang, The Affiliated Hospital of XuZhou Medical University, Lianyungang, Jiangsu, 222002, People’s Republic of China; 3Department of Operating Room, Wuxi People’s Hospital, Wuxi, Jiangsu, 214063, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Qian Department of Operating Room, Wuxi People’s Hospital, No. 299 Qingyang Road, Liangxi District, Wuxi, 214063, Jiangsu, People’s Republic of China, Tel +8615190209358, Email qianying_q06@126.comObjective: We aimed to analyze the factors related to delay in transfer of patients in the post-anesthesia care unit (PACU) and to develop and validate a prediction model for understanding these factors to guide precise clinical intervention.Methods: We collected data from two cohorts of 1153 and 297 patients who underwent surgery and were treated in the PACU at two time points. We examined their clinical features and anesthesia care data using analytical methods such as logistic regression, Random Forest, and eXtreme Gradient Boosting (Xgboost) to screen out variables and establish a prediction model. We then validated and simplified the model and plotted a nomogram. Using LASSO regression, we reduced the dimensionality of the data. We developed multiple models and plotted receiver operating characteristic (ROC) and calibration curves. We then constructed a simplified model by pooling the identified variables, which included hemoglobin (HB), alanine transaminase (ALT), glucose levels, duration of anesthesia, and the minimum bispectral index value (BIS_min).Results: The model had good prediction performance parameters in the training and validation sets, with an AUC of 0.909 (0.887– 0.932) in the training set and 0.939 (0.919– 0.959) in the validation set. When we compared model 6 with other models, the net reclassification index (NRI) and the integrated discriminant improvement (IDI) index indicated that it did not differ significantly from the other models. We developed a scoring system, and it showed good prediction performance when verified with the training and validation sets as well as external data. Additionally, both the decision curve analysis (DCA) and clinical impact curve (CIC) demonstrated the potential clinical efficacy of the model in guiding patient interventions.Conclusion: Predicting transfer delays in the post-anesthesia care unit using predictive models is feasible; however, this merits further exploration.Keywords: delayed transfer, machine learning, nomogram, post-anesthesia care unit, predictive model

Jiali Lu,1,2,&ast; Fei Li,3,&ast; Mei Ye1,2 1Department of Gastroenterology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 2Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 3Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei Ye, Department of Gastroenterology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China, Email wumeiye08@163.comBackground: Ulcerative colitis (UC) is an autoimmune inflammatory disorder of the gastrointestinal tract. Programmed cell death (PCD), including PANoptosis and autophagy, plays roles in inflammation and immunity. This study aimed to investigate the molecular signature and immune landscape of the PANoptosis- and autophagy-related differentially expressed genes (DEGs) in UC.Methods: Analyzing UC dataset GSE206285 yielded DEGs. Differentially expressed PANoptosis- and autophagy-related genes were identified using DEGs and relevant gene collections. Functional and pathway enrichment analyses were conducted. A protein-protein interaction (PPI) network was established to identify hub genes. TRRUST database predicted transcription factors (TFs), pivotal miRNAs, and drugs interacting with hub genes. Immune infiltration analysis, UC-associated single-cell sequencing data analysis, and construction of a competing endogenous RNA (ceRNA) network for hub genes were conducted. Machine learning identified key candidate genes, evaluated for diagnostic value via receiver operating characteristic (ROC) curves. A UC mice model verified expression of key candidate genes.Results: Identifying ten PANoptosis-related hub DEGs and four autophagy-related hub DEGs associated them with cell chemotaxis, wound healing and positive MAPK cascade regulation. Immune infiltration analysis revealed increased immunocyte infiltration in UC patients, with hub genes closely linked to various immune cell infiltrations. Machine learning identified five key candidate genes, TIMP1, TIMP2, TIMP3, IL6, and CCL2, with strong diagnostic performance. At the single-cell level, these genes exhibited high expression in inflammatory fibroblasts (IAFs). They showed significant expression differences in the colon mucosa of both UC patients and UC mice model.Conclusion: This study identified and validated novel molecular signatures associated with PANoptosis and autophagy in UC, potentially influencing immune dysregulation and wound healing, thus opening avenues for future research and therapeutic interventions.Keywords: ulcerative colitis, PANoptosis, autophagy, immune cell infiltration, inflammatory fibroblasts, bioinformatics analysis

Yanhua Liu,1,2,&ast; Fuxing Li,1,2,&ast; Youling Fang,2,3 Qiaoshi Zhong,1,2 Yanping Xiao,1,2 Yunwei Zheng,1,2 Junqi Zhu,2,3 Chuwen Zhao,2,3 Xingwei Cao,1,2 Jianqiu Xiong,4 Longhua Hu1,2 1The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi, Nanchang, People’s Republic of China; 2Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, People’s Republic of China; 3School of Public Health, Nanchang University, Jiangxi, Nanchang, People’s Republic of China; 4Department of Nursing, the Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianqiu Xiong, Department of Nursing, The Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Jiangxi, Nanchang, 330006, People’s Republic of China, Email 1773014059@qq.com Longhua Hu, Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Jiangxi, Nanchang, 330006, People’s Republic of China, Email longhuahu@163.comObjective: This research aimed to analyze the clinical characteristics, prognosis, and antimicrobial treatment of bloodstream infections (BSI) caused by Enterobacter cloacae complex (ECC).Methods: The clinical data of patients with bloodstream infections caused by Enterobacter cloacae complex from April 2017 to June 2023 were collected retrospectively. These data were then analyzed in subgroups based on the detection results of extended-spectrum β-lactamase (ESBL), 30-day mortality, and the type of antimicrobial agent used (β-lactam/β-lactamase inhibitor combinations (BLICs) or carbapenems).Results: The proportion of ESBL-producing Enterobacter cloacae complex was 32.5% (37/114). Meanwhile, ICU admission, receiving surgical treatment within 3 months, and biliary tract infection were identified as risk factors for ESBL-producing ECC-BSI. Additionally, immunocompromised status and Sequential Organ Failure Assessment (SOFA) score ≥ 6.0 were identified as independent risk factors of 30-day mortality in patients with ECC-BSI (n = 108). Further analysis in BSI patients caused by non-ESBL-producing ECC revealed that patients treated with BLICs (n = 45) had lower SOFA scores and lower incidence of hypoproteinemia and sepsis compared with patients treated with carbapenems (n = 20). Moreover, in non-ESBL-producing ECC-BSI patients, the univariate Cox regression analysis indicated a significantly lower 30-day mortality rate in patients treated with BLICs compared to those treated with carbapenems (hazard ratios (HR) [95% CI] 0.190 [0.055– 0.662], P = 0.009; adjusted HR [95% CI] 0.106 [0.013– 0.863], P = 0.036).Conclusion: This study investigated the factors influencing the susceptibility to infection by ESBL-producing strains and risk factors for 30-day mortality in ECC-BSI patients. The results revealed that ESBL-negative ECC-BSI patients treated with BLICs exhibited significantly lower 30-day mortality compared to those treated with carbapenems. BLICs were found to be more effective in ECC-BSI patients with milder disease (ESBL-negative and SOFA ≤ 6.0).Keywords: Enterobacter cloacae complex, extended-spectrum β-lactamase, bloodstream infection, risk factors, β-lactam/β- lactamase inhibitor combinations, carbapenems

Yinan Cao,1– 3,&ast; Fan Li,1– 3,&ast; Zhenxuan Sun,1– 3 Jin Liu,1– 3 Jie Liu,1– 3 Qi Yang,1– 3 Peng Ge,1– 3 Yalan Luo,1– 3 Hailong Chen1– 3 1Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 2Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116044, People’s Republic of China; 3Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yalan Luo; Hailong Chen, Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Zhongshan Road 222, Dalian, 116011, Liaoning, People’s Republic of China, Tel +86-411-83635963, Fax +86-411-83622844, Email luoyalanxueshu@163.com; chenhailong@dmu.edu.cnPurpose: Explore the therapeutic effects and regulatory mechanism of Qingyi Decoction (QYD) on severe acute pancreatitis (SAP) associated acute lung injury (ALI).Methods: We identified the constituents absorbed into the blood of QYD based on a network pharmacological strategy. The differentially expressed genes from the GEO database were screened to identify the critical targets of QYD treatment of SAP-ALI. The SAP-ALI rat model was constructed.Some methods were used to evaluate the efficacy and mechanism of QYD in treating SAP-ALI. LPS-stimulated pulmonary microvascular endothelial cell injury simulated the SAP-induced pulmonary endothelial injury model. We further observed the therapeutic effect of QYD and CDK5 plasmid transfection on endothelial cell injury.Results: 18 constituents were absorbed into the blood, and 764 targets were identified from QYD, 25 of which were considered core targets for treating SAP-ALI. CDK5 was identified as the most critical gene. The results of differential expression analysis showed that the mRNA expression level of CDK5 in the blood of SAP patients was significantly up-regulated compared with that of healthy people. Animal experiments have demonstrated that QYD can alleviate pancreatic and lung injury inflammatory response and reduce the upregulation of CDK5 in lung tissue. QYD or CDK5 inhibitors could decrease the expression of NFAT5 and GEF-H1, and increase the expression of ACE-tub in SAP rat lung tissue. Cell experiments proved that QYD could inhibit the expression of TNF-α and IL-6 induced by LPS. Immunofluorescence results suggested that QYD could alleviate the cytoskeleton damage of endothelial cells, and the mechanism might be related to the inhibition of CDK5-mediated activation of NFAT5, GEF-H1, and ACE-tub.Conclusion: CDK5 has been identified as a critical target for pulmonary endothelial injury of SAP-ALI. QYD may partially alleviate microtubule disassembly by targeting the CDK5/NFAT5/GEF-H1 signaling pathway, thus relieving SAP-induced pulmonary microvascular endothelial cell injury. Keywords: Qingyi decoction, severe acute pancreatitis, acute lung injury, CDK5, microtubule

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

Suqing Liu,1 Fengling Li,1 Qinghua Cao,2 Ning Li,1 Qian Gao1 1Department of Gynaecology and Obstetrics, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, People’s Republic of China; 2Department of Pathology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, People’s Republic of ChinaCorrespondence: Fengling Li, Department of Gynecology and Obstetrics, Yantai Affiliated Hospital of Binzhou Medical University, Muping District, Yantai, Shandong, People’s Republic of China, Email sdbzlsq1989@163.comAbstract: Gastric adenocarcinoma (GAS) is a rare subtype of mucinous adenocarcinoma characterized by gastric differentiation and is unrelated to human papillomavirus (HPV) infection. This report discusses a 40-year-old female who presented with abdominal distension accompanied by increased abdominal circumference. CT of the abdomen and pelvis showed a large 21.0&ast;12.7&ast;26.0 cm mass later diagnosed as GAS combined with squamous cell carcinoma on surgical pathology. Immunohistological staining of GAS was positive for CK7, MUC6, PAX-8 CEA, and P53 (wild type) and negative for CDX2, CK20, ER, PR, P16, and WT1. The proliferative index (Ki-67) was 20%. Immunohistochemical staining of squamous cell carcinoma was positive for P16 and P53 (wild type), and the proliferative index (Ki-67) was 90%. However, the pathogenesis and molecular mechanisms of GAS have not been fully elucidated. As more cases are identified and reported, additional targeted therapies can be developed and tested in these patients.Keywords: cervical cancer, gastric type, adenocarcinoma

Xue-Song Xiong,1,2,&ast; Xue-Di Zhang,3,&ast; Jia-Wei Yan,3 Ting-Ting Huang,1,2 Zhan-Zhong Liu,4 Zheng-Kang Li,5 Liang Wang,5 Fen Li1,2 1Department of Laboratory Medicine, The Affiliated Huai’an Hospital of Yangzhou University, Huai’an, Jiangsu Province, People’s Republic of China; 2Department of Laboratory Medicine, The Fifth People’s Hospital of Huai’an, Huai’an, Jiangsu Province, People’s Republic of China; 3Department of Laboratory Medicine, Xuzhou Infectious Diseases Hospital, Xuzhou, Jiangsu Province, People’s Republic of China; 4Department of Pharmacy, Xuzhou Infectious Diseases Hospital, Xuzhou, Jiangsu Province, People’s Republic of China; 5Department of Laboratory Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Wang; Fen Li, Email healthscience@foxmail.com; 3063892835@qq.comAbstract: Multidrug-resistant tuberculosis (MDR-TB) is an essential cause of tuberculosis treatment failure and death of tuberculosis patients. The rapid and reliable profiling of Mycobacterium tuberculosis (MTB) drug resistance in the early stage is a critical research area for public health. Then, most traditional approaches for detecting MTB are time-consuming and costly, leading to the inappropriate therapeutic schedule resting on the ambiguous information of MTB drug resistance, increasing patient economic burden, morbidity, and mortality. Therefore, novel diagnosis methods are frequently required to meet the emerging challenges of MTB drug resistance distinguish. Considering the difficulty in treating MDR-TB, it is urgently required for the development of rapid and accurate methods in the identification of drug resistance profiles of MTB in clinical diagnosis. This review discussed recent advances in MTB drug resistance detection, focusing on developing emerging approaches and their applications in tangled clinical situations. In particular, a brief overview of antibiotic resistance to MTB was present, referred to as intrinsic bacterial resistance, consisting of cell wall barriers and efflux pumping action and acquired resistance caused by genetic mutations. Then, different drug susceptibility test (DST) methods were described, including phenotype DST, genotype DST and novel DST methods. The phenotype DST includes nitrate reductase assay, RocheTM solid ratio method, and liquid culture method and genotype DST includes fluorescent PCR, GeneXpert, PCR reverse dot hybridization, ddPCR, next-generation sequencing and gene chips. Then, novel DST methods were described, including metabolism testing, cell-free DNA probe, CRISPR assay, and spectral analysis technique. The limitations, challenges, and perspectives of different techniques for drug resistance are also discussed. These methods significantly improve the detection sensitivity and accuracy of multidrug-resistant tuberculosis (MRT) and can effectively curb the incidence of drug-resistant tuberculosis and accelerate the process of tuberculosis eradication. Keywords: MTB, antibiotic resistance, Raman spectroscopy, rapid detection

Fan Li,1– 3,&ast; Zhengjian Wang,4,&ast; Yinan Cao,1– 3 Boliang Pei,1– 3 Xinyu Luo,1– 3 Jin Liu,1– 3 Peng Ge,1– 3 Yalan Luo,1– 3 Shurong Ma,1,3 Hailong Chen1– 3 1Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 2Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 3Laboratory of Integrative Medicine, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116011, People’s Republic of China; 4Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shurong Ma; Hailong Chen, Department of General Surgery, the First Affiliated Hospital of Dalian Medical University, Zhongshan Road 222, Dalian, Liaoning, 116011, People’s Republic of China, Tel +86-411-83635963, Fax +86-411-83622844, Email shurongma94@163.com; chenhailong@dmu.edu.cnAbstract: The pathogenesis of severe acute pancreatitis-associated acute lung injury (SAP-ALI), which is the leading cause of mortality among hospitalized patients in the intensive care unit, remains incompletely elucidated. The intestinal mucosal immune barrier is a crucial component of the intestinal epithelial barrier, and its aberrant activation contributes to the induction of sustained pro-inflammatory immune responses, paradoxical intercellular communication, and bacterial translocation. In this review, we firstly provide a comprehensive overview of the composition of the intestinal mucosal immune barrier and its pivotal roles in the pathogenesis of SAP-ALI. Secondly, the mechanisms of its crosstalk with gut microbiota, which is called gut-lung axis, and its effect on SAP-ALI were summarized. Finally, a number of drugs that could enhance the intestinal mucosal immune barrier and exhibit potential anti-SAP-ALI activities were presented, including probiotics, glutamine, enteral nutrition, and traditional Chinese medicine (TCM). The aim is to offer a theoretical framework based on the perspective of the intestinal mucosal immune barrier to protect against SAP-ALI.Keywords: severe acute pancreatitis-associated acute lung injury, intestinal mucosal immune barrier, gut microbiota, gut-lung axis, migration of immune cells

Xiaoying Meng,1,2 Fei Li,2 Wenpei Wu,3 Juncang Wu1,2 1Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University (Hefei Second People’s Hospital), Hefei, Anhui, 230011, People’s Republic of China; 2The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 3Department of Neurology, Hefei Second People’s Hospital Affiliated to Bengbu Medical College, Hefei, Anhui, 230011, People’s Republic of ChinaCorrespondence: Juncang Wu, Department of Neurology, Hefei Hospital Affiliated to Anhui Medical University (Hefei Second People’s Hospital), Hefei, Anhui, 230011, People’s Republic of China, Email wujuncang126@126.comPurpose: To investigate the quantitative assessment of carotid plaque by each parameter of dual-layer detector spectral CT and its diagnostic value in patients with acute cerebral infarction.Patients and Methods: Eighty-three patients with carotid atherosclerotic plaques who underwent spectral CT scanning were retrospectively included. Forty-two patients with acute ischaemic stroke (AIS) were included in the study group, and 41 patients without AIS were included in the control group. We compared the detection of carotid plaques in the two groups and the differences in the spectral quantitative parameters of the plaques in the two groups, and their diagnostic efficacy was obtained.Results: The detection rate of carotid plaques in the AIS group was higher than that in the non-AIS group (p< 0.05); the carotid plaques in the AIS group mainly consisted of non-calcified plaques, while those in the non-AIS group mainly consisted of calcified plaques. The effective atomic number (Zeff), slope of the energy spectrum curve (λH), electron density (ED), and iodine-no-water value of the carotid plaques in the AIS group were lower than those in the non-AIS (p< 0.05). For the differentiation of the carotid plaques in the AIS group from those in the non-AIS group, the area under the curve (AUC) of Zeff amounted to 0.637 (cut-off value: 11.865; sensitivity: 72.5%; specificity: 56.2%), the AUC of λH amounted to 0.628 (cut-off value: 19.56; sensitivity: 76.3%; specificity: 51.6%), and that for ED amounted to 0.624 (cut-off value: 110.45; sensitivity: 60.0%; specificity: 64.1%), AUC of iodine-no-water value amounted to 0.645 (cut-off value: 9.125; sensitivity: 61.3%; specificity: 65.6%).Conclusion: In summary, the quantitative parameters of dual-layer detector spectral CT can be used to assess plaque stability and have certain value in the diagnosis of AIS. The quantitative parameters can effectively differentiate carotid plaques in AIS and non-AIS patients.Keywords: ischemic stroke, carotid plaque, spectral CT, effective atomic number, iodine density values, anhydrous iodine values, electron density

Ruichen Fang,1,2 Yihong Cheng,1,2 Fan Li,3 Yan Xu,1,2 Yuanhui Li,4 Xiang Liu,4 Simin Guo,4 Yuling Wang,1,2 Jinnong Jiang,1,2 Dan Zhou,1,2 Bin Zhang1,2 1Department of Psychiatry, Sleep Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Key Laboratory of Mental Health of the Ministry of Education, Guangzhou, People’s Republic of China; 3School of Biomedical Engineering, Faculty of Medicine, Dalian University of Technology, Dalian, 116024, People’s Republic of China; 4Adai Technology (Beijing) Co., Ltd, Beijing, People’s Republic of ChinaCorrespondence: Bin Zhang, Department of Psychiatry, Sleep Medicine Center, Nanfang Hospital, No. 1838 North, Guangzhou Avenue, Guangzhou, 510515, People’s Republic of China, Email zhang73bin@hotmail.comPurpose: In this study, we established the Chinese Clinical Sleep Database (CCSD), aiming to provide a safe, scalable, and user-friendly database that includes high-quality clinical data from Chinese population to facilitate sleep research.Material and Methods: We collect individual’s demographic data, scales, anthropometric measurements, clinical diagnosis, and polysomnography (PSG) recordings from the routine medical process of sleep medicine centers using standardized procedures. The distributed cluster storage technology are utilized to store these data. The structured data are stored in a high-performance MySQL database, while the unstructured data are stored in an object storage service. And we have developed an online data platform to share and manage our data.Results: The data collection has been conducted in three hospitals. In the preliminary stage of data collection (from October 18, 2022 to September 4, 2023), our database included a total of 1183 patients. Among them, 56.8% were male and their ages ranged from 3 to 88 years. These patients were diagnosed with various types of sleep disorders.Conclusion: Since the CCSD’s inception, it has demonstrated good stability, security, and scalability. As an public database, the CCSD also exhibits user-friendliness. The CCSD contains comprehensive clinical data, which can contribute to the advancement of the diagnosis and treatment strategies for sleep disorders, ultimately promoting sleep health.Keywords: sleep medicine, methodology, database, data collection, collaboration tool

Cantao Li,&ast; Chenxi Wu,&ast; Fenfen Li, Wenjing Xu, Xiaoxi Zhang, Yan Huang, Daozong Xia School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daozong Xia, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Baichuan Street, Fuyang District, Hangzhou, Zhejiang Province, People’s Republic of China, Email xdz_zjtcm@hotmail.comAbstract: Gouty arthritis (GA) is an immune-mediated disorder characterized by severe inflammation due to the deposition of monosodium urate (MSU) crystals in the joints. The pathophysiological mechanisms of GA are not yet fully understood, and therefore, the identification of effective therapeutic targets is of paramount importance. Neutrophil extracellular traps (NETs), an intricate structure of DNA scaffold, encompassing myeloperoxidase, histones, and elastases - have gained significant attention as a prospective therapeutic target for gouty arthritis, due to their innate antimicrobial and immunomodulatory properties. Hence, exploring the therapeutic potential of NETs in gouty arthritis remains an enticing avenue for further investigation. During the process of gouty arthritis, the formation of NETs triggers the release of inflammatory cytokines, thereby contributing to the inflammatory response, while MSU crystals and cytokines are sequestered and degraded by the aggregation of NETs. Here, we provide a concise summary of the inflammatory processes underlying the initiation and resolution of gouty arthritis mediated by NETs. Furthermore, this review presents an overview of the current pharmacological approaches for treating gouty arthritis and summarizes the potential of natural and synthetic product-based inhibitors that target NET formation as novel therapeutic options, alongside elucidating the intrinsic challenges of these inhibitors in NETs research. Lastly, the limitations of HL-60 cell as a suitable substitute of neutrophils in NETs research are summarized and discussed. Series of recommendations are provided, strategically oriented towards guiding future investigations to effectively address these concerns. These findings will contribute to an enhanced comprehension of the interplay between NETs and GA, facilitating the proposition of innovative therapeutic strategies and novel approaches for the management of GA. Keywords: neutrophils, neutrophil extracellular traps, gouty arthritis, inflammation, NETs inhibitor

Jing Yang,1,&ast; Dixia Hu,2,&ast; Kaige Yin,3 Fang Li,4 Dongyan Shi5 1Hebei Provincial Center for Clinical Laboratories, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Clinical Lab, Zhangjiakou First Hospital, Zhangjiakou, People’s Republic of China; 3Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Department of Pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 5Department of Clinical Lab, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongyan Shi, Email shidongyan73@126.comBackground: Nocardia farcinica, a pathogen known for its strong pathogenicity, is frequently implicated in skin, central nervous system, and lung infections among immunosuppressed hosts, while intestinal nocardiosis is rare. We report the case of infectious diarrhea caused by N. farcinica in a child.Case Presentation: A 19-month-old female child was admitted to the hospital with fever and diarrhea after the consumption of oranges. The etiological agent responsible for the diarrhea was identified through the examination of fecal smears using weak acid-fast staining and conducting fecal cultures. Whole-genome sequencing was employed to analyze the causative gene. Subsequent to a 5-day treatment regimen with amoxicillin-clavulanate at a dosage of 30 mg/kg every 12 hours, the child’s condition improved significantly, leading to an uncomplicated discharge.Conclusion: This case illustrates the presence of intestine virulence factors in N. farcinica capable of causing diarrhea. The utilization of weak acid-fast staining in the examination of fecal smears is crucial for the accurate diagnosis of infectious diarrhea caused by Nocardia spp.Keywords: Nocardia farcinica, diarrhea, virulence factors

Xinyi Long,1 Fangfang Li,1 Sishi Tang,1 Jing Liu,1 Yunfeng Fu,2 Yanhui Feng3 1Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, 410013, People’s Republic of China; 2Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha, 410013, People’s Republic of China; 3Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, 410013, People’s Republic of ChinaCorrespondence: Yanhui Feng, Department of Oncology, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Hexi, Changsha, Hunan Province, People’s Republic of China, Tel +86-13549656766, Email fengyanhui900@sohu.comPurpose: Immunological regimens are an important area of research for treating multiple myeloma (MM). Plasma cells play a crucial role in immunotherapy.Patients and Methods: In our study, we used both single-cell RNA sequencing (scRNA-seq) and bulk sequencing techniques to analyze MM patients. We analyzed each sample using gene set variation analysis (GSVA) based on immune-related gene sets. We also conducted further analyses to compare immune infiltration, clinical characteristics, and expression of immune checkpoint molecules between the H-S100A9 and L-S100A9 groups of MM patients.Results: We identified eight subpopulations of plasma cells, with S100A9 plasma cells being more abundant in patients with 1q21 gain and 1q21 diploid. CellChat analysis revealed that GAS and HGF signaling pathways were prominent in intercellular communication of S100A9 plasma cells. We identified 14 immune-related genes in the S100A9 plasma cell population, which allowed us to classify patients into the H-S100A9 group or the L-S100A9 group. The H-S100A9 group showed higher ESTIMATE, immune and stroma scores, lower tumor purity, and greater immune checkpoint expression. Patients with 1q21 gain and four or more copies had the lowest ESTIMATE score, immune score, stroma score, and highest tumor purity. Drug sensitivity analysis indicated that the H-S100A9 group had lower IC50 values and greater drug sensitivity compared to the L-S100A9 group. Quantitative reverse transcription (RT-q) PCR showed significantly elevated expression of RNASE6, LYZ, S100A8, S100A9, and S100A12 in MM patients compared to the healthy control group.Conclusion: Our study has identified a correlation between molecular subtypes of S100A9 plasma cells and the response to immunotherapy in MM patients. These findings improve our understanding of tumor immunology and provide guidance for developing effective immunotherapy strategies for this patient population.Keywords: multiple myeloma, single-cell sequencing, bulk transcription, tumor immune microenvironment, S100A9

Danyang Fan, Fuqiu Li, Zhe Liu, Zhanhan Tang, Sha Lv Department of Dermatology, The Second Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of ChinaCorrespondence: Sha Lv, Department of Dermatology, The second hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China, Email lvsha@jlu.edu.cnAbstract: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disease mainly manifested as skin and osteoarticular lesions. Herein, we describe a female patient with SAPHO syndrome exhibited paradoxical psoriasis and primary palmoplantar pustulosis (PPP) worsened during treatment with adalimumab. We then switched to secukinumab and obtained significant improvement in both skin lesions and osteoarticular pain. These findings suggest that secukinumab might be an appropriate option for patients with SAPHO syndrome who present with TNF-α-inhibitor-induced paradoxical psoriasis.Keywords: SAPHO syndrome, psoriasis, adalimumab, secukinumab

Shifeng Sheng,1 Jingfeng Chen,1 Yuheng Zhang,1 Weikang Li,1 Feifei Li,1 Rong Gou,2 Lin Tang,2 Suying Ding1 1Health Management Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Lin Tang, Department of Nephropathy, The First Affiliated Hospital of Zhengzhou University, No. 1 Longhu Middle Ring Road, Jinshui District, Zhengzhou, 450052, People’s Republic of China, Tel +86 13783623040, Email tanglin@zzu.edu.cn Suying Ding, Health Management Center, The First Affiliated Hospital of Zhengzhou University, No. 1 Longhu Middle Ring Road, Jinshui District, Zhengzhou, 450052, People’s Republic of China, Tel +86 15838023097, Email fccdingsy@zzu.edu.cnObjective: To explore the correlation between serum uric acid (SUA) trajectories and new-onset hypertension, to provide scientific basis for the prevention and treatment of hypertension.Methods: The study cohort was composed of 4372 subjects who met the inclusion criteria in the cohort study of Henan physical examination population. According to the SUA values of the subjects’ physical examination from 2017 to 2019, three different SUA trajectory groups were determined by R LCTM tools, namely low stability group, medium stability group and high stability group. The incidence of hypertension during physical examination in 2020 was followed up, the cumulative incidence rate in each group was calculated by product limit method, and the correlation between different SUA trajectories and new-onset hypertension was analyzed by Cox proportional hazards regression model.Results: The incidence rate of hypertension increased with the increase of SUA locus, which was 4.65%, 9.18% and 12.43% respectively, and the difference was statistically significant (P< 0.001). After adjusting multiple confounding factors, such as gender, waist circumference (WC), blood pressure, body mass index (BMI), fasting plasma glucose (FPG) and blood lipid by Cox proportional hazards regression model, the risk of hypertension in SUA medium stability and high stability group was still 1.476 times ( 95% CI: 1.089~2.000) and 1.692 times ( 95% CI: 1.152~2.484) of low-stable SUA group (P< 0.05).Conclusion: The risk of hypertension increases with the increase of SUA level in the long-term normal range. It is necessary to carry out the intervention for hypertension with long-term normal high value to avoid the progress of hypertension disease, to achieve the purpose of early prevention of hypertension.Keywords: uric acid, hypertension, trajectories, correlation, health physical examination

Naigeng Wang,1 Fei Li,2 Jing Du,3 Jianhong Hao,1 Xin Wang,2 Yueru Hou,3 Zhenguo Luo1 1Department of Anesthesiology, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China; 3Second Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, People’s Republic of ChinaCorrespondence: Zhenguo Luo, Email luozhenguo@stu.xjtu.edu.cnBackground: This study aims to investigate the protective effect of quercetin against global cerebral ischemia‒reperfusion (GCI/R) injury in rats and elucidate the underlying mechanism.Methods: A GCI/R injury rat model was established using a four-vessel occlusion (4-VO) method. An oxygen–glucose deprivation/reoxygenation (OGD/R) injury model was induced in BV2 cells. The extent of injury was assessed by evaluating neurological deficit scores (NDS) and brain water content and conducting behavioral tests. Pathomorphological changes in the prefrontal cortex were examined. Additionally, the study measured the levels of inflammatory cytokines, the degree of microglial activation and polarization, and the protein expression of Toll-like receptor 4 (TLR4) and TIR-domain-containing adaptor inducing interferon-β (TRIF).Results: Quercetin pretreatment significantly ameliorated neurological impairment, improved learning and memory abilities, and reduced anxiety in rats subjected to GCI/R injury. Furthermore, quercetin administration effectively mitigated neuronal injury and brain edema. Notably, it suppressed microglial activation and hindered polarization toward the M1 phenotype. Simultaneously, quercetin downregulated the expression of TLR4 and TRIF proteins and attenuated the release of IL-1β and TNF-α.Conclusion: This study highlights the novel therapeutic potential of quercetin in alleviating GCI/R injury. Quercetin demonstrates its neuroprotective effects by inhibiting neuroinflammation and microglial activation while impeding their transformation into the M1 phenotype through modulation of the TLR4/TRIF pathway.Keywords: quercetin, cerebral ischemia, neuroprotection, neuroinflammation

Xi Liu,1,2 Haihui Zhuang,1,2 Fenglin Li,1,2 Ying Lu,1,2 Renzhi Pei1,2 1Department of Hematology, The Affiliated People’s Hospital of Ningbo University, Ningbo, People’s Republic of China; 2Institute of Hematology, Ningbo University, Ningbo, People’s Republic of ChinaCorrespondence: Ying Lu; Renzhi Pei, Tel +86-574-87016871 ; Tel +86-574-87016870, Email rmluying@nbu.edu.cn; peirz@163.comBackground: Recently, an increasing number of studies have suggested dual-specificity phosphatase 23 (DUSP23) is a critical factor in the development of diffuse connective tissue disease and may be a valuable biomarker for primary human cancers. However, there is a lack of comprehensive studies on the prognostic significance of DUSP23 expression in acute myeloid leukemia (AML).Methods: RNA sequencing data from The Cancer Genome Atlas (TCGA) (AML = 173), Genotype-Tissue Expression (GTEx) (healthy controls = 70) and GEO (AML = 461, healthy controls = 76) databases were used to compare DUSP23 expression between AML patients and healthy controls. The overall survival (OS) of DUSP23 in AML was evaluated using Kaplan-Meier Cox regression. Furthermore, univariate Cox regression and multivariate Cox regression analysis were used to determine whether DUSP23 was an independent prognostic factor for AML. We then verified the expression level and prognostic significance of DUSP23 in our cohort (AML = 128, healthy controls = 31). In addition, functional enrichment analysis of DUSP23-related DEGs was performed through gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network analysis.Results: The expression level of DUSP23 is significantly higher in AML patients than in healthy controls in TCGA, GTEx, GEO databases and our cohort. By multivariate analysis, high expression of DUSP23 is a poor prognostic indicator of OS in the TCGA database. Next, we verified the role of DUSP23 as an adverse prognostic biomarker in our cohort. Enrichment analysis of related genes showed that DUSP23 may regulate important signal pathways in hematological tumors including the MAPK pathways. It is suggested by the PPI network that DUSP23, along with IMP3, MRPL4, MRPS12, POLR2L, and ATP5F1D may play a role in the process of AML.Conclusion: The study demonstrated high expression of DUSP23 could serve as a poor independent prognostic biomarker in AML.Keywords: DUSP23, expression, prognosis, AML, bioinformatics

Kebing Lv,1,&ast; Xiaoye Cheng,1– 3,&ast; Yulan Zhou,1– 3 Min Yu,1– 3 Shixuan Wang,1– 3 Huimin Shen,1 Fei Li1– 3 1Center of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Jiangxi Clinical Research Center for Hematologic Disease, Nanchang, People’s Republic of China; 3Institute of Lymphoma and Myeloma, Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Li, Email ndyfy01238@ncu.edu.cnBackground: Hemophagocytic lymphohistiocytosis (HLH) patients who need intensive care usually have multiple organ failure and poor prognosis. However, the clinical characteristics, therapeutic efficacy and outcome in these critically ill HLH patients have remained unclear.Methods: We performed a retrospective study of 50 critically ill HLH patients from September 2013 to October 2022. Patients’ information was collected, and the overall survival rate was estimated.Results: Fifty HLH patients need intensive care, and the median sequential organ failure assessment (SOFA) score was 8. 66.00% patients had septic shock, 60.00% had disseminated intravascular coagulation (DIC) and 56.00% had acute respiratory distress syndrome (ARDS). 64.00% patients needed vasoactive drugs, 60.00% needed invasive or non-invasive positive pressure mechanical ventilation, and 12.00% needed continuous renal replacement therapy (CRRT). Among 18 patients received the etoposide-based regimens, the median time for 17 patients to remove ECG monitoring was 13 days (4– 30 days); the median time to remove respiratory support in 10 patients was 8.5 days (4– 21 days); the median time for 5 patient to convert from dominant DIC to non-dominant DIC was 4 days (1– 14 days) and the median time for 6 patients to stop using vasoactive drugs was 10 days (2– 14 days). After 4 weeks of treatment, 7 patients were evaluated as NR, 6 achieved PR, and 5 could not be evaluated. The ORR was 55.56%. Up to the last follow-up, the OS rate of patients receiving etoposide-based regimens was 66.67%. In contrast, all 32 HLH patients in other groups died. Univariate analysis showed that PCT > 0.5 ug/L, PT prolonged > 6 s, TBil > 25umol/L, respiratory failure, renal failure, liver failure and did not receive etoposide- based regimens were the negative factors affecting survival (P = 0.001, 0.017, 0.043, 0.001, 0.000, 0.029, 0.000).Conclusion: HLH patients who need intensive care timely used etoposide-based HLH regimens might rescue critically ill patients successfully.Keywords: hemophagocytic lymphohistiocytosis, etoposide-based treatment, critically ill patients, prognosis

Huajun Sun,1 Fangshi Li,1 Yaxuan Xu,2 Qi Qi,3 Yue Du1 1School of Public Health, Tianjin Medical University, Tianjin, People’s Republic of China; 2School of Nursing, Tianjin Medical University, Tianjin, People’s Republic of China; 3School of Optometry, Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Yue Du, School of Public Health, Tianjin Medical University, 22&num; Qixiangtai Road, Heping District, Tianjin, 300070, People’s Republic of China, Tel +86 18920015698, Fax +86 02283336597, Email duyue@tmu.edu.cnObjective: Physical examination services play a crucial role in the early detection of diseases, improving the effectiveness of treatment. However, the current physical examination services provided by community health service centers are limited. The objective of this study was to investigate the aspects of physical examination services that are most valued by residents.Methods: Identify and develop attributes and levels through literature research and expert group interviews. A discrete choice experiment was designed. The main effects design gives rise to 16 choice sets. The 16 choice sets were grouped into 2 blocks, and respondents were randomly assigned to one of the blocks. In each choice set, respondents were asked to choose from two alternatives with an opt-out option. In 2023, the discrete choice experiment was administered in several community health service centers within a China population sample. A mixed logit and a latent class analysis were conducted.Results: Participants (n = 399) preferred to receive health advice service. The services provided by the basic team with clinical experts are preferred over those provided solely by the basic team. The results indicated a preference for a participant to be serviced by face-to-face or telephone compared with WeChat. Low cost is also preferred. As participants grow older, their preference for face-to-face or telephone-based services increased. As participants’ service demand increase, participants more preferred to receive interpretation of physical examination report and follow-up of important abnormal results, participants more preferred to be serviced by basic team with clinical experts or basic team with health manager etc.Conclusion: We should improve the construction of the service team, optimize the service mode, expand the scope of examination services, reduce the cost of examination services, and meet the needs of residents for physical examination services. More attention should be paid to the needs of elderly and rural residents.Keywords: discrete choice experiment, physical examination, community health service, preference

Fenge Li,1,2,&ast; Yupeng Wang,1,&ast; Jin Yan,1,&ast; Huancheng Wu,3 Xueming Du,1 Weihong Feng,1 Xiaoqing Zhang,4 Yongming Xue,4 Huaqing Wang,5,6 Wenxin Liu7 1Department of Oncology, Tianjin Beichen Hospital Tianjin People’s Republic of China; 2Core Laboratory, Tianjin Beichen Hospital, Tianjin, People’s Republic of China; 3Department of Neurosurgery, Tianjin Beichen Hospital, Tianjin, People’s Republic of China; 4Department of Basic Research, Suzhou Lanma Biotechnology Co, Suzhou, People’s Republic of China; 5Department of Oncology, Tianjin Union Medical Center, Tianjin, People’s Republic of China; 6Department of Translational Medicine, Tianjin Union Medical Center of Nankai University, Tianjin, People’s Republic of China; 7Department of Gynecological Oncology, Tianjin Medical Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenxin Liu, Department of Gynecological Oncology, Tianjin Medical Cancer Institute and Hospital, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin, People’s Republic of China, Tel +8618622221101, Email wenxin1973@163.com Huaqing Wang, Department of Translational Medicine, Tianjin Union Medical Center of Nankai University, Jieyuan Road No. 190, Nankai District, Tianjin, People’s Republic of China, Tel +8618622221223, Email huaqingw@163.comIntroduction: Tumor-infiltrating lymphocytes (TILs) therapy is one of the most promising adoptive T cell therapies, which has shown great clinical efficacy against several solid malignancies. Nevertheless, clinical response to TILs mono-therapy in Asian patients with recurrent cervical cancer has not been well reported.Case Presentation: Here, we report two patients who were diagnosed with metastatic cervical cancer and tumor progression following multiple conventional treatments. In particular, one of the patients has a history of severe myelosuppression after chemotherapy. The patients received lymphodepletion therapy, which consisted of cyclophosphamide (30mg/kg) for 2 days, followed by Fludarabine (25mg/m2) for 5 days, approximately 24 hr before receiving intravenous autologous TILs infusion. These two patients then received high doses of IL-2 for 10 days with the purpose of maintaining T cell survival and proliferation. Patient 1 experienced clinical partial response (PR) at 6 weeks post TILs infusion and a 33% tumor shrinkage at 12 weeks follow-up, and patient 2 was evaluated as stable disease (SD) at 6 weeks post treatment. Mild and manageable adverse events were observed and soon subsided after the TILs treatment. A time-course study examining the peripheral blood cell count and cytokine secretion demonstrated the persistence of infused TILs and long-term immune response.Conclusion: These results suggest that TILs mono-therapy can be a promising treatment strategy for Asian patients with late-stage metastatic cervical cancer even with severe myelosuppression. TILs infusion can induce persistence and a long-term systematic immune response that reversed peripheral CD4+T and CD8+T percentages implying that TILs infusion increased cytotic T cell responses, which is consistent with clinical responses in these patients. Trial registration number: NCT05366478.Keywords: tumor-infiltrating lymphocytes, clinical response, immune response, metastatic cervical cancer, treatment

Jiaqi Meng,1 Weichang Yang,2 Ziyong Chen,1 Caixia Pei,1 Xinmin Peng,1 Can Li,1 Fengyuan Li1 1Department of Respiratory and Critical Care Medicine, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330008, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of ChinaCorrespondence: Can Li; Fengyuan Li, The First Hospital of Nanchang, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email 407329399@qq.com; lifengyuan@126.comPurpose: To investigate the value of apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and ApoA1/B ratio in pathogenic diagnosis of chronic obstructive pulmonary disease (COPD) complicated by acute lower respiratory tract infection, assisting comprehensive disease assessment.Patients and Methods: The study enrolled 171 COPD patients with acute lower respiratory tract infections, 35 COPD patients without acute lower respiratory tract infections, and 41 healthy controls. Correlation analysis and binary logistic regression were used to assess the roles of various factors in COPD with acute lower respiratory tract infections. Receiver operating characteristic (ROC) curves were plotted and area under curves (AUC) values were calculated to evaluate the predictive performance.Results: Infections were the cause of alterations in ApoA1, ApoB and ApoA1/B index. In correlation analysis for pathogenic diagnosis of COPD complicated by acute lower respiratory infections, age, ApoA1, ApoA1/B ratio, lymphocyte count (LYMPH), neutrophil count (NEUT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and endotoxin were significantly correlated. For predicting COPD complicated by acute lower respiratory tract bacterial infection, ApoA1 had the highest area under the ROC curve (AUC: 0.889), with sensitivity and specificity of 82.9% and 83.9%, respectively. The combination of NEUT and ApoA1 improved the prediction efficacy (AUC: 0.909; sensitivity/specificity: 85.1%/85.7%).Conclusion: ApoA1, ApoB, and ApoA1/B ratio are good indicators for predicting pathogens in COPD complicated by acute lower respiratory tract infection, especially ApoA1 which has high predictive value.Keywords: ApoA1, ApoB, ApoA1/B, COPD, Acute lower respiratory tract infection, pathogens

Mingxuan Zou,1,2,&ast; Bin Liu,2,&ast; Jing Ji,1 Lei Ren,3,4 Xiuchao Wang,2 Fengzhan Li2 1Public Health School, Shaanxi University of Chinese Medicine, Xianyang, 712046, People’s Republic of China; 2Department of Military Medical Psychology, Air Force Medical University, Xi’ an, 710032, People’s Republic of China; 3Military Psychology Section, Logistics University of PAP, Tianjin, 300309, People’s Republic of China; 4Military Mental Health Services & Research Center, Tianjin, 300309, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengzhan Li; Xiuchao Wang, Email psyfengzhan@126.com; Wangxiuchao1984@163.comBackground: Military personnel experience prolonged exposure to high-stress environments. Positive coping styles can assist in maintaining their mental and behavioral well-being, whereas negative coping styles cannot. Health behavior change theory specifies that an individual can transition from a negative to a positive coping style. The psychological resilience concept may prove vital in this transition.Methods: In a longitudinal study design, two questionnaires were administered to 233 military personnel twice, the first at T1 in April 2023 and the second at T2 in July 2023. The questionnaire measured individual negative coping style, positive coping style and psychological resilience.Results: The data showed that the negative coping style at T1 negatively predicted the level of psychological resilience at T2 (γ= - 0.26, p < 0.001) and the positive coping style at T2 (γ= - 0.16, p < 0.001). The level of psychological resilience at T1 positively predicted the positive coping style at T2 (γ= 0.22, p < 0.01). Psychological resilience played a mediating role between negative coping style and positive coping style. In addition, there was an interaction between psychological resilience and positive coping style in military personnel at the two time points.Conclusion: The negative coping styles that presently exist among military personnel have the potential to diminish their future positive coping styles by lowering their psychological resilience. This highlights the need to focus on the development and training of psychological resilience for military personnel, as it can effectively counteract negative coping styles and promote positive coping styles.Keywords: military personnel, coping style, resilience, cross-lagged analysis

Siming Tao,1,&ast; Jing Jing,1,2,&ast; Yide Wang,1,3,&ast; Fengsen Li,1,2 Hongxia Ma1,2 1Department of Respiratory and Critical Care Medicine, Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2Xinjiang Laboratory of Respiratory Disease Research, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, People’s Republic of China; 3Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengsen Li; Hongxia Ma, Department of Respiratory and Critical Care Medicine, Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi, 830000, People’s Republic of China, Tel +86 13999980996 ; +86 13999995669, Email fengsen602@163.com; jasmine0991@163.comObjective: Endoplasmic reticulum stress (ERS) is key in chronic obstructive pulmonary disease (COPD) incidence and progression. This study aims to identify potential ERS-related genes in COPD through bioinformatics analysis and clinical experiments.Methods: We first obtained a COPD-related mRNA expression dataset (GSE38974) from the Gene Expression Omnibus (GEO) database. The R software was then used to identify potential differentially expressed genes (DEGs) of COPD-related ERS (COPDERS). Subsequently, the identified DEGs were subjected to protein-protein interaction (PPI), correlation, Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Following that, qRT-PCR was used to examine the RNA expression of six ERS-related DEGs in blood samples obtained from the COPD and control groups. The genes were also subjected to microRNA analysis. Finally, a correlation analysis was performed between the DEGs and key clinical indicators.Results: Six ERS-related DEGs (five upregulated and one downregulated) were identified based on samples drawn from 23 COPD patients and nine healthy individuals enrolled in the study. Enrichment analysis revealed multiple ERS-related pathways. The qRT-PCR and mRNA microarray bioinformatics analysis results showed consistent STC2, APAF1, BAX, and PTPN1 expressions in the COPD and control groups. Additionally, hsa-miR-485-5p was identified through microRNA prediction and DEG analysis. A correlation analysis between key genes and clinical indicators in COPD patients demonstrated that STC2 was positively and negatively correlated with eosinophil count (EOS) and lymphocyte count (LYM), respectively. On the other hand, PTPN1 showed a strong correlation with pulmonary function indicators.Conclusion: Four COPDERS-related key genes (STC2, APAF1, BAX, and PTPN1) were identified through bioinformatics analysis and clinical validation, and the expressions of some genes exhibited a significant correlation with the selected clinical indicators. Furthermore, hsa-miR-485-5p was identified as a potential key target in COPDERS, but its precise mechanism remains unclear.Keywords: endoplasmic reticulum stress, chronic obstructive pulmonary disease, bioinformatics analysis, clinical prediction

Xin Su,1,&ast; Hengqiong Gu,1,&ast; Fajun Li,2 Donglei Shi,3 Zhaojun Wang3 1Department of Respiratory, Hainan Hospital of PLA General Hospital, Sanya, People’s Republic of China; 2Department of Critical Care Medicine, The First People’s Hospital of Kunshan, Kunshan, People’s Republic of China; 3Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Donglei Shi; Zhaojun Wang, Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, 628 Zhenyuan Road, Shenzhen, 518107, People’s Republic of China, Tel/Fax +86-755-81206874, Email shidlei@mail.sysu.edu.cn; wangzhj55@mail.sysu.edu.cnBackground: A study aimed to estimate the burden of Chronic obstructive pulmonary disease (COPD) caused by occupational exposure to particulate matter, gases, and fumes in 204 countries from 1990 to 2019.Methods: Data on the deaths number, age-standardized mortality rates (ASMR), and age-standardized disability-adjusted life years (DALYs) rates (ASDR) of COPD attributable to occupational particulate matter, gases, and fumes were collected from the GBD study 2019. We also investigated the association between the ASDR and SDI.Results: There were 517.7 thousand deaths [95% UI: 413.9 to 634.5] in 2019. The number of deaths increased from 1990 to 2019. The ASMR and ASDR were 6.61 (5.24 to 8.17) and 143.02 (118.56 to 168.69) in 2019, respectively, representing a 46% and 44.5% decrease since 1990. China had the highest number of deaths [200,748.4 (151,897.6 to 260,703.9)], while Nepal had the highest ASMR [39 (27.7 to 50)] and ASDR [724.5 (549 to 894.2)]. Males and females 75– 79 and 80– 84 years old had the highest number of COPD deaths. A negative correlation was observed when SDI > 0.4, whereas a positive correlation was found when SDI < 0.4.Conclusion: From 1990 to 2019, there was an increase in the number of deaths, but a decline in ASMR and ASDR globally. Besides, there was a heterogeneous burden of COPD attributable to occupational particulate matter, gases, and fumes across regions and countries. It is important to develop and implement strategies to prevent and reduce the burden of COPD attributable to occupational particulate matter, gases, and fumes.Keywords: chronic obstructive pulmonary disease, occupational particulate matter, gases, fumes, global burden of disease, deaths number, age-standardized rates

Min Jiang,1,&ast; NanNan Pang,2,&ast; Jing Wang,1 Zheng Li,1 Dan Xu,1 Jing Jing,1 Dan Chen,3 Fengsen Li,1 Jianbing Ding,4 Qifeng Li5 1Xinjiang Key Laboratory of Respiratory Disease Research, Traditional Chinese Medical Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830011, Xinjiang, People’s Republic of China; 2CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, People’s Republic of China; 3School of Public Health, Xinjiang Medical University, Urumqi, 830017, Xinjiang, People’s Republic of China; 4Department of Immunology, College of Basic Medicine, Xinjiang Medical University, Urumqi, 830011, Xinjiang, People’s Republic of China; 5Xinjiang Institute of Pediatrics, Xinjiang Hospital of Beijing Children’s Hospital, Children’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830011, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qifeng Li, Xinjiang Institute of Pediatrics, Xinjiang Hospital of Beijing Children’s Hospital, Children’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830054, People’s Republic of China, Tel +86-991 3056239, Fax +86-991 3056237, Email liqiqi521@sina.comBackground: Studying the potential etiology and pathogenesis of tuberculosis-associated chronic obstructive pulmonary disease (TOPD) from an autoimmunity perspective may provide insights into peripheral blood autoantibodies and immune cells, as well as their interactions.Methods: This study examined the serum autoantibody repertoire in healthy individuals, patients with chronic obstructive pulmonary disease (COPD), patients with pulmonary tuberculosis (TB), and TOPD patients using the HuProtTM protein chip. Autoantigens in the peripheral blood of TOPD patients were verified using ELISA assay. Various epitopes and immune simulation were predicted using bioinformatic methods. Flow cytometry was employed to detect macrophages(M&phis;), T cells, and innate lymphoid cells (ILCs) in the peripheral blood.Results: COPD patients displayed distinct alterations in their IgG and IgM autoantibodies compared to the other groups. GeneOntology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses revealed that these autoantibodies were associated with regulating macrophages, T cells, and B cells. ELISA results confirmed the upregulation of expression of proliferating cell nuclear antigen (PCNA), Mitogen-Activated Protein Kinase 3 antigen (MAPK3), and threonine protein kinase 1 antigen (AKT1) proteins in the peripheral blood of TOPD patients. Bioinformatic analysis predicted multiple potential epitopes in Th, CTL, and B cells. Immune simulation results demonstrated that PCNA, MAPK3, and AKT1 can activate innate and adaptive immune responses and induce the expression of different cytokines, such as IFN-g and IL-2. Furthermore, data obtained from flow cytometry assay revealed an upregulation in the face of Th1 cells in the peripheral blood of TOPD patients.Conclusion: Tuberculosis infection can effectively induce autoimmune responses, contributing to increased expression of Th1 cells and associated cytokines, ultimately leading to immune dysregulation. Furthermore, the accumulation of pulmonary inflammatory response facilitates the progression of TOPD and is helpful for the clinical diagnosis and the development of targeted therapeutic drugs for this disease.Keywords: chronic obstructive pulmonary disease, COPD, autoantibody, autoimmunity, inflammatory phenotype

Ye Wang,1,&ast; Fenxiang Li,1,&ast; Jian Liu,2 Jing Liu,3 Pei Qin,4 Jiayi Zhang,5 Yingtao Zhang,5 Shuning Wu6 1Department of Epidemiology, School of Medicine, Jinan University, Guangzhou, People’s Republic of China; 2Department of General Surgery, Maternal and Child Health Hospital, Qingyuan, Guangdong, People’s Republic of China; 3Intensive Care Unit 1, The First Affiliated Hospital, Jinan University, Guangdong, Guangzhou, People’s Republic of China; 4Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, People’s Republic of China; 5Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, People’s Republic of China; 6Department of Thyroid and Breast Surgery, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingtao Zhang, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, 510000, People’s Republic of China, Tel +86 15918805867, Email zhangyt9@mail2.sysu.edu.cn Shuning Wu, Thyroid and Breast Surgical Department, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, 518067, People’s Republic of China, Tel +86 13480209989, Email jessica540wu@outlook.comPurpose: This study aims to identify common COVID-19 symptoms and asymptomatic infection rates during the epidemic in China. We also introduce the concepts of “Time-point asymptomatic rate” and “Period asymptomatic rate”.Object and Methods: A questionnaire survey was conducted online from December 2022 to January 5, 2023, collecting demographic characteristics, laboratory results, clinical symptoms, lifestyle and vaccination history. Statistical methods were used to analyze symptom characteristics, associated factors, and patterns during an 8-day observation period. Numerical variables were described by median M (Q1-Q3) or mean and standard deviation (). Categorical variables are described by frequency (N), ratio (%) or rate (%). The influencing factors were studied by Wilcoxon or Kruskal-Willis H rank sum test or logistic regression analysis, and the trend of symptom incidence by Spearman rank correlation. P value being ≤ 0.05 was statistically significant.Results: Out of 536 participants, 493 (91.98%) were infected, with 3 asymptomatic cases and 490 symptomatic cases within 8 days. The time-point asymptomatic rate increased from 0.61% on day 1 to 15.42% on day 8. Fever, cough, and fatigue were the main symptoms, with additional symptoms such as vomiting, diarrhea, and hyposmia reported. Symptom durations varied, with cough and expectoration lasting longer and vomiting and diarrhea lasting shorter. Several symptoms showed a downward trend over time.Conclusion: Our online survey highlighted that most COVID-19 patients experienced symptoms, and the time-point asymptomatic rate showed a dynamic change among the infected population. Onset patterns and demographic factors influence symptom occurrence and duration. These findings have implications for clinical practitioners and decision-makers in public health measures and strategies.Keywords: Novel coronavirus infection, onset patterns, clinical features, associated factors, time-point asymptomatic, period asymptomatic rate

Qun Xu,1 Fangzhou Li,2 Xujiao Chen2,3 1School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Geriatrics, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 3Zhejiang Hospital, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xujiao Chen, Department of Geriatrics, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, Zhejiang, 310003, Email lily197459@163.comPurpose: Corona Virus Disease 2019 (COVID-19) endangers the health and survival of the elderly. We tried to explore factors especially kidney function which affected mortality in elderly hypertensive patients with COVID-19.Methods: We conducted a retrospective research of 748 COVID-19 elderly patients (≥ 65 years old) at Zhejiang Hospital. This study compared demographic data, laboratory values, comorbidities, treatments, and clinical outcomes of hypertension and non-hypertension participants, and subgroup analysis of age and frailty was conducted in the hypertension population. Survival analysis was used to determine risk factors for death in elderly patients with COVID-19.Results: Our study revealed that the elderly hypertensive patients with COVID-19 had higher blood urea nitrogen (BUN), serum uric acid (UA), serum creatinine (Scr), lower estimated glomerular filtration rate (eGFR), higher incidence of severity, admission to intensive care unit (ICU) and death, and longer in-hospital stay than non-hypertensive patients, which also occurred in the very elderly hypertensive patients compared with younger hypertensive patients and frail hypertensive patients compared with no-frail hypertensive patients. In addition, the prevalence of acute kidney injury (AKI) was higher in the oldest old hypertensive patients and frail hypertensive patients. Multivariate survival analysis indicated that the independent risk factors for death from COVID-19 were age ≥ 80 years, heart failure, antiviral therapy, calcium channel blocker (CCB) therapy, mechanical ventilation, AKI, and eGFR< 60 mL/min per 1.73 m2.Conclusion: The results of the present study suggested that the elderly hypertensive patients with COVID-19 would have more serious kidney injury, more serious disease progression and higher mortality, which also occurred in very elderly and frailty subgroup. Kidney dysfunction was closely related to mortality in elderly patients with COVID-19.Keywords: mortality, kidney dysfunction, frailty, elderly, hypertensive hospitalized patients with COVID-19

Mei Cong,1,&ast; Houjun Pang,1,2,&ast; Guangxing Xie,1 Feifei Li,3 Chunxiao Li,3 Hao Sun,3 Shaoyou Yang,1 Weidong Zhao3 1School of Pharmacy, Xinxiang Medical University, Xinxiang, People’s Republic of China; 2Department of Pharmacy, Dazhou Women and Children’s Hospital, Dazhou, People’s Republic of China; 3Henan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weidong Zhao, Henan Key Laboratory of Immunology and Targeted Drugs, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China, Tel +86 0373 3029977, Fax +86 0373 3029977, Email 141051@xxmu.edu.cnPurpose: Molecular targeted therapy is one of the most pivotal strategies in the treatment of non-small cell lung cancer, yet its curative effect is severely compromised by the poor aqueous solubility, low bioavailability and inadequate tumor accumulation of targeted agents. To enhance the efficacy of targeted agents, we demonstrate a novel self-assemble amphiphilic molecule based on erlotinib as an effective nanodrug for anti-cancer treatment.Methods: An amphiphilic molecule composed of hydrophobic erlotinib and hydrophilic biotin block was synthesized and characterized by nuclear magnetic resonance (NMR) as well as high-resolution mass spectrometry (HRMS). Then, nanoassemblies of the amphiphilic molecules are formulated by using nanoprecipitation method. Subsequently, the size, morphology, cell uptake, the anticancer activity and in vivo distribution of the newly constructed erlotinib nanodrug were systematically assessed by some methods, including transmission electron microscopy (TEM), dynamic light-scattering (DLS), flow cytometry, in vivo imaging system etc.Results: We developed a novel nanoformulation of erlotinib, which possesses a high drug loading of 45%. With the features of well-defined structure and small size, the obtained nanodrug could be effectively accumulated in tumor sites and rapidly internalized by cancer cells. Finally, the erlotinib-based nanoformulation showed considerably better anticancer activity compared to free erlotinib both in vitro and in vivo. Moreover, the nanodrug displayed great tolerability.Conclusion: Combining the advantageous features of both nanotechnology and self-assemble, this novel erlotinib nanomedicine constitutes a promising therapeutic candidate for cancer treatment. This study also underlines the potential use of amphiphilic molecule for improving drug efficacy as well as reducing drug toxicity, which could become a general strategy for the preparation of nanodrugs of active agents.Keywords: erlotinib, amphiphilic molecule, self-assembling, drug self-delivery system, non-small cell lung cancer

Fuchun Li Fourth Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of ChinaCorrespondence: Fuchun Li, Fourth Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Str, Nangang District, Harbin, 150001, People’s Republic of China, Email lifuchunhb@163.comPurpose: To assess if metformin could reduce the risk of total hip arthroplasty (THA) in elderly patients with hip osteoarthritis and type 2 diabetes (T2DM).Patients and Methods: It is a retrospective study among elderly patients (≥ 65 years) with hip osteoarthritis and T2DM. All included patients were divided into metformin group and non-metformin group, then propensity-score match (PSM) was performed to control potential confounding factors. The primary endpoint was the incidence of the first THA during the study period. Multivariate Cox regression analysis was employed to evaluate the association of metformin with the risk of THA.Results: A matched cohort of 716 patients were finally included, with 308 metformin users and 308 metformin non-users. During a maximum follow-up of 10 years, the incidence of THA in metformin users was significantly lower than that in non-users (4.9% vs 25.0%, P< 0.01). Multivariate Cox regression analysis indicated that metformin users were significantly associated with a lower risk of THA compared with non-users (HR = 0.17, 95% CI: 0.10– 0.30; P< 0.01). In addition, further analyses indicated that participants with long-term metformin use (HR = 0.10, 95% CI: 0.02– 0.46; P< 0.01) or high metformin dosage (HR = 0.15, 95% CI: 0.04– 0.57; P< 0.01) had a lower risk of THA.Conclusion: Metformin use could reduce the risk of THA in patients with hip osteoarthritis and T2DM, and the effect is accumulative and dose dependent.Keywords: hip osteoarthritis, total hip arthroplasty, type 2 diabetes, metformin