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Jia-wei Xu,1,2,* Fang-fang Chen,1,* Ying-hui Qv,1,* Cong-cong Sun,1 Dong Zhang,1,2 Zhi Guo,1 Yu-jiao Wang,3 Jun-fei Wang,4 Tian Liu,4 Liang Dong,1,2 Qian Qi1,2 1Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Shandong Characteristic Laboratory of Clinical Transformation of Respiratory Biological Immunity and Regenerative Medicine, Jinan, Shandong Province, 250014, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong Province, 250014, People’s Republic of China; 3Department of Clinical Laboratory Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Laboratory Medicine, Jinan, Shandong Province, 250014, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, Shandong Province, 250012, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian Qi, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, #16766, Jingshi Road, Jinan City, Shandong Province, 250014, People’s Republic of China, Tel +86 13706380314, Email qiqianqlh@163.comPurpose: Bronchiectasis patients are prone to Pseudomonas aeruginosa infection due to decreased level of sphingosine in airway. Adiponectin receptor agonist AdipoRon activates the intrinsic ceramidase activity of adiponectin receptor 1 (AdipoR1) and positively regulates sphingosine metabolism. This study aimed to investigate the potential therapeutic benefit of AdipoRon against Pseudomonas aeruginosa infection.Methods: A mouse model of Pseudomonas aeruginosa lung infection and a co-culture model of human bronchial epithelial cells with Pseudomonas aeruginosa were established to explore the protective effect of AdipoRon. Liquid chromatography-mass spectrometry was used to detect the effect of AdipoRon on sphingosine level in lung of Pseudomonas aeruginosa-infected mouse models.Results: The down-regulation of adiponectin and AdipoR1 in airway of bronchiectasis patients was linked to Pseudomonas aeruginosa infection. By activating AdipoR1, AdipoRon reduced Pseudomonas aeruginosa adherence on bronchial epithelial cells and protected cilia from damage in vitro. With the treatment of AdipoRon, the load of Pseudomonas aeruginosa in lung significantly decreased, and peribronchial inflammatory cell infiltration was lessened in vivo. The reduced level of sphingosine in the airway of Pseudomonas aeruginosa infected mice was replenished by AdipoRon, thus playing a protective role in the airway. Moreover, AdipoRon activated P-AMPKα/PGC1α, inhibited TLR4/P-NF-κB p65, and reduced expression of pro-apoptotic bax. However, the protective effect of AdipoRon on resisting Pseudomonas aeruginosa infection was weakened when AdipoR1 was knocked down.Conclusion: AdipoRon protects bronchial epithelial cells and lung by enhancing their resistance to Pseudomonas aeruginosa infection. The mechanism might be modulating sphingosine metabolism and activating P-AMPKα/PGC1α while inhibiting TLR4/P-NF-κB p65.Keywords: AdipoRon, Pseudomonas aeruginosa, bronchiectasis, AdipoR1, sphingosine metabolism

Haotian Xin,1,2 Beining Yang,1,2 Yulong Jia,1,2 Qunya Qi,1,2 Yu Wang,1,2 Ling Wang,1,2 Xin Chen,1,2 Fang Li,3 Jie Lu,1,2 Nan Chen1,2 1Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 2Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, 100053, People’s Republic of China; 3Department of Rehabilitation Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of ChinaCorrespondence: Nan Chen, Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, No. 45 Chang-Chun St, Xicheng District, Beijing, People’s Republic of China, Tel +86 13910784187, Email chenzen8057@sina.comAbstract: Neuropathic pain (NP) is a common and persistent disease that leads to immense suffering and serious social burden. Incomplete understanding of the underlying neural basis makes it difficult to achieve significant breakthroughs in the treatment of NP. We aimed to review the functional and structural brain topological properties in patients with NP and consider how graph measures reveal potential mechanisms and are applied to clinical practice. Related studies were searched in PubMed and Web of Science databases. Topological property changes in patients with NP, including small-worldness, functional separation, integration, and centrality metrics, were reviewed. The findings suggest that NP was characterized by retained but declined small-worldness, indicating an insidious imbalance between network integration and segregation. The global-level measures revealed decreased global and local efficiency in the NP, implying decreased information transfer efficiency for both long- and short-range connections. Altered nodal centrality measures involve various brain regions, mostly those associated with pain, cognition, and emotion. Graph theory is a powerful tool for identifying topological properties of patients with NP. These specific brain changes in patients with NP are very helpful in revealing the potential mechanisms of NP, developing new treatment strategies, and evaluating the efficacy and prognosis of NP.Keywords: neuropathic pain, graph theory, brain network, magnetic resonance imaging

Shuangjin Liu, Zihao Zeng, Qi Qi, Qin Yang, Yiqiu Hu School of Educational Science, Hunan Normal University, Changsha, 410006, People’s Republic of ChinaCorrespondence: Yiqiu Hu, School of Educational Science, Hunan Normal University, Changsha, 410006, People’s Republic of China, Email fortune2000947@163.comBackground: Based on the gene-environment interaction paradigm, this study explored the effect of peer relationships on adolescent loneliness and the role of psychological resilience and the oxytocin receptor gene (OXTR).Methods: A survey was conducted in a sample of 619 adolescents, and their oral cells were collected for DNA extraction and genotyping.Results: The results showed that (1) both peer relationships and psychological resilience significantly affected adolescent loneliness; (2) psychological resilience partially mediated the relationship between peer relationships and loneliness in adolescents; (3) OXTR gene rs53576 polymorphism moderated both the first and second half of the indirect pathway of the mediation model. Specifically, carriers of the rs53576 polymorphism A/A genotype showed a significantly enhanced effect of peer relationships on adolescent psychological resilience, while carriers of the rs53576 polymorphism G/G genotype showed a significantly enhanced effect of psychological resilience on adolescent loneliness.Conclusion: These findings helped elucidate the developmental mechanisms of adolescent loneliness in terms of peer relationships, psychological resilience, and OXTR gene polymorphisms.Plain Language Summary: A moderated mediation effects analysis was conducted to investigate the effect of peer relationships on adolescent loneliness and the role of psychological resilience and the oxytocin receptor gene (OXTR). The results revealed psychological resilience partially mediated the relationship between peer relationships and loneliness in adolescents; OXTR gene rs53576 polymorphism moderated both the first and second half of the indirect pathway of the mediation model. These findings helped elucidate the developmental mechanisms of adolescent loneliness in terms of peer relationships, psychological resilience, and OXTR gene polymorphisms.Keywords: peer relationship, adolescents, loneliness, psychological resilience, OXTR gene

Qi Qi,* Jun Yang,* Linhui Yang, Huohuan Tian, Chun Wan, Dan Liu Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dan Liu; Chun Wan, Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, People’s Republic of China, Email liudan10965@wchscu.cn; wanchun66@wchscu.cnAbstract: Lemierre syndrome (LS) is a rare and life-threatening condition predominantly caused by Fusobacterium necrophorum. Currently, there are no standardized clinical guidelines for LS management. Here, we describe the case of a 40-year-old male with fever, productive cough, and dyspnea but no sore throat. Diagnostic radiological examinations revealed multiple pulmonary cavitary nodules and an internal jugular vein occlusion. Metagenomic Next-Generation Sequencing (mNGS) of the alveolar lavage fluid identified Fusobacterium necrophorum, thereby confirming the diagnosis of LS. Intriguingly, the patient exhibited a delayed clinical response despite receiving the appropriate antibiotic. After integrating tigecycline into the treatment to address potential co-infecting bacteria, we observed a marked improvement in his clinical symptoms. Subsequent follow-up over 12 weeks post-discharge revealed complete alleviation of symptoms, and a chest CT scan showed marked regression of the lung lesions.Keywords: Lemierre syndrome, Fusobacterium necrophorum, septic thrombophlebitis, antibiotic therapy, anticoagulation

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# 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

Chenglin Miao,1,* Yali Cui,1– 3,* Yingying Li,1 Qianqian Qi,1 Wenling Shang,1 Huilian Chen,2,3 Yujie Gao,2,3 Ruomei Yuan,2,3 Qichen Long,4 Wenjing Wu,1 Xia Wang,1 Ziyi Yan,1 Yongmei Jiang1,5 1Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Laboratory Medicine, Meishan Women and Children’s Hospital, Alliance Hospital of West China Second University Hospital, Sichuan University, Meishan, Sichuan Province, People’s Republic of China; 3Department of Laboratory Medicine, West China Second University Hospital (Tianfu), Sichuan University/Sichuan Provincial Children’s Hospital, Meishan, Sichuan Province, People’s Republic of China; 4Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 5Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ziyi Yan; Yongmei Jiang, Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China, Tel +86 28 8857050 ; +86 28 85501543, Email yan_z_y2@qq.com; jiangyongmeiwst@163.comPurpose: This study was designed to evaluate the immune protective efficacy of the novel Streptococcus pneumoniae (S. pneumoniae) protein vaccine PiuA-PlyD4 through immunoinformatics prediction and in vitro and in vivo experiments.Methods: In this study, we conducted immunoinformatics prediction and protection analysis on the fusion protein PiuA-PlyD4. The epitope composition of the vaccine was analyzed based on the prediction of B-cell and helper T-cell epitopes. Meanwhile, the molecular docking of PiuA and TLR2/4 was simulated. After immunizing C57BL/6 mice with the prepared vaccine, the biological safety, immunogenicity and conservation were evaluated. By constructing different infection models and from the aspects of adhesion inhibition and cytokines, the protective effect of the fusion protein vaccine PiuA-PlyD4 on S. pneumoniae infection was explored.Results: PiuA-PlyD4 has abundant B-cell and helper T-cell epitopes and shows a high antigenicity score and structural stability. Molecular docking analysis suggested the potential interaction between PiuA and TLR2/4. The specific antibody titer of fusion protein antiserum was as high as (7.81± 2.32) × 105. The protective effect of the immunized mice on nasal and lung colonization was significantly better than that of the control group, and the survival rate against S. pneumoniae infection of serotype 3 reached 50%. Cytokine detection showed that the humoral immune response, Th1, Th2 and Th17 cellular immune pathways were all involved in the process.Conclusion: The study indicates that PiuA-PlyD4, whether the results are predicted by immunoinformatics or experimentally validated in vivo and in vitro, has good immunogenicity and immunoreactivity and can provide effective protection against S. pneumoniae infection. Therefore, it can be considered a promising prophylactic vaccine candidate for S. pneumoniae.Keywords: Streptococcus pneumoniae, fusion protein vaccine, PiuA-PlyD4, immunoinformatics prediction, protective efficacy

Qian Qi,1,2,* Jiawei Xu,1,2,* Yujiao Wang,3,* Jian Zhang,1 Mingxia Gao,1 Yu Li,4 Liang Dong1,2 1Department of Respiratory, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Respiratory Diseases, Jinan, Shandong Province, People’s Republic of China; 2Department of Respiratory, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong Province, People’s Republic of China; 3Department of Clinical Laboratory Medicine, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong Province, People’s Republic of China; 4Department of Respiratory, Qilu Hospital, Shandong University, Jinan, Shandong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang Dong, Department of Respiratory, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, #16766, Jingshi Road, Jinan, Shandong Province, 250014, People’s Republic of China, Tel +86 13505401207, Email dl5506@126.comPurpose: To assess the metabolites associated with Pseudomonas aeruginosa infection by analyzing the microbial diversity and metabolomics in lower respiratory tract of bronchiectasis patients and to explore the therapeutic approaches for Pseudomonas aeruginosa infection.Methods: Bronchoalveolar lavage fluid samples from bronchiectasis patients and controls were analyzed by 16S rRNA and ITS sequencing, and metabolomic analysis was performed by liquid chromatography/mass spectrometry. A co-culture model of air-liquid interface cultured human bronchial epithelial cell with Pseudomonas aeruginosa was constructed to verify the correlation between sphingosine metabolism, acid ceramidase expression, and Pseudomonas aeruginosa infection.Results: After screening, 54 bronchiectasis patients and 12 healthy controls were included. Sphingosine levels in bronchoalveolar lavage fluid were positively correlated with lower respiratory tract microbial diversity and negatively correlated with the abundance of Pseudomonas spp. Moreover, sphingosine levels in bronchoalveolar lavage fluid and acid ceramidase expression levels in lung tissue specimens were significantly lower in bronchiectasis patients than in healthy controls. Sphingosine levels and acid ceramidase expression levels were also significantly lower in bronchiectasis patients with positive Pseudomonas aeruginosa cultures than in bronchiectasis patients without Pseudomonas aeruginosa infection. Acid ceramidase expression in air-liquid interface cultured human bronchial epithelial cell had significantly increased after 6 h of Pseudomonas aeruginosa infection, while it had decreased significantly after 24 h of infection. In vitro experiments showed that sphingosine had a bactericidal effect on Pseudomonas aeruginosa by directly disrupting its cell wall and cell membrane. Furthermore, adherence of Pseudomonas aeruginosa on bronchial epithelial cells was significantly reduced after sphingosine supplementation.Conclusion: Down-regulation of acid ceramidase expression in airway epithelial cells of bronchiectasis patients leads to insufficient metabolism of sphingosine, which has a bactericidal effect, and consequently weakens the clearance of Pseudomonas aeruginosa; thus, a vicious circle is formed. Exogenous supplementation with sphingosine aids bronchial epithelial cells in resisting Pseudomonas aeruginosa infection.Keywords: metabolomics, bronchiectasis, sphingosine, Pseudomonas aeruginosa, acid ceramidase

Tianyu Yu,* Jiangnan Dong,* Qi Qi,* Qiang Lv, Jun Li, Chaojun Huang, Xiaoyan Cai Department of General Surgery, Gongli Hospital of Shanghai Pudong New Area, Shanghai, 200135, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoyan Cai, Department of General Surgery, Gongli Hospital of Shanghai Pudong New Area, Shanghai, 200135, People’s Republic of China, Tel/Fax +86-21-58858730, Email cxy6429@163.comPurpose: The Omicron variant of SARS-CoV-2 has emerged as a significant global concern, characterized by its rapid transmission and resistance to existing treatments and vaccines. However, the specific hematological and biochemical factors that may impact the clearance of Omicron variant infection remain unclear. The present study aimed to identify easily accessible laboratory markers that are associated with prolonged virus shedding in non-severe patients with COVID-19 caused by the Omicron variant.Patients and Methods: A retrospective cohort study was conducted on 882 non-severe COVID-19 patients who were diagnosed with the Omicron variant in Shanghai between March and June 2022. The least absolute shrinkage and selection operator regression model was used for feature selection and dimensional reduction, and multivariate logistic regression analysis was performed to construct a nomogram for predicting the risk of prolonged SARS-CoV-2 RNA positivity lasting for more than 7 days. The receiver operating characteristic (ROC) curve and calibration curves were used to assess predictive discrimination and accuracy, with bootstrap validation.Results: Patients were randomly divided into derivation (70%, n = 618) and validation (30%, n = 264) cohorts. Optimal independent markers for prolonged viral shedding time (VST) over 7 days were identified as Age, C-reactive protein (CRP), platelet count, leukocyte count, lymphocyte count, and eosinophil count. These factors were subsequently incorporated into the nomogram utilizing bootstrap validation. The area under the curve (AUC) in the derivation (0.761) and validation (0.756) cohorts indicated good discriminative ability. The calibration curve showed good agreement between the nomogram-predicted and actual patients with VST over 7 days.Conclusion: Our study confirmed six factors associated with delayed VST in non-severe SARS-CoV-2 Omicron infection and constructed a Nomogram which may assist non-severely affected patients to better estimate the appropriate length of self-isolation and optimize their self-management strategies.Keywords: SARS-CoV-2, COVID-19, Omicron, viral shedding time, nomogram

Lingzhou Zhao,* Jiali Gong,* Qinli Qi,* Changcun Liu, Hongxing Su, Yan Xing, Jinhua Zhao Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinhua Zhao; Yan Xing, Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, People’s Republic of China, Tel/Fax +86 21 3779 8352, Email zhaojinhua1963@126.com; xy.1@163.comPurpose: The unique structure of nanobodies is advantageous for the development of radiopharmaceuticals for nuclear medicine. Nanobodies targeted to human epidermal growth factor receptor 2 (HER2) can be used as tools for the imaging and therapy of HER2-overexpressing tumors. In this study, we aimed to describe the generation of a 131I-labeled anti-HER2 nanobody as a targeted radionuclide therapy (TRNT) agent for HER2-positive breast cancer.Methods: The anti-HER2 nanobody NM-02 was labeled with 131I using the iodogen method, and its radiochemical purity and stability in vitro were assessed. The pharmacokinetic profile of 131I-NM-02 was investigated in normal mice. Tumor accumulation, biodistribution, and therapeutic potential of 131I-NM-02 were evaluated in HER2-positive SKBR3 xenografts; HER2-negative MB-MDA-231 xenografts were used as the control group.Results: 131I-NM-02 could be readily prepared with satisfactory radiochemical purity and stability in vitro. Apparent tumor uptake was observed in HER2-positive tumor-bearing mice with rapid blood clearance and favorable biodistribution. 131I-NM-02 could significantly inhibit tumor growth and extend the life of these mice with good organ compatibility. Negligible tumor accumulation and inhibitory effects of 131I-NM-02 were observed in the negative control group.Conclusion: 131I-NM-02 has the potential to be explored as a novel tool for TRNT of HER2-positive breast cancer.Keywords: human epidermal growth factor receptor 2, nanobody, 131I, targeted radionuclide therapy

Yining Xiao,1– 3 Zhenjie Teng,1– 3 Jing Xu,2,3 Qianqian Qi,2 Tianyuan Guan,1,2 Xin Jiang,2,3 Huifang Chen,2 Xiaohua Xie,2 Yanhong Dong,2,3 Peiyuan Lv1– 3 1Department of Neurology, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Hebei Provincial Key Laboratory of Cerebral Networks and Cognitive Disorders, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Peiyuan Lv, Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China, Email peiyuanlu2@163.comObjective: This study sought to explore the associations of the systemic immune-inflammation index (SII) with total cerebral small vessel disease (CSVD) burden and cognitive impairment.Methods: We enrolled 201 patients in the retrospective study with complete clinical and laboratory data. The SII was calculated as platelet count × neutrophil count/lymphocyte count. Cognitive function was evaluated by the Mini-Mental State Examination (MMSE). Total CSVD burden was assessed based on magnetic resonance imaging. We performed logistic regression models, Spearman correlation, and mediation analysis to evaluate the associations of SII with CSVD burden and cognitive impairment.Results: After adjustment for confounding factors in the multivariate binary logistic regression model, elevated SII (odds ratio [OR], 3.263; 95% confidence interval [CI], 1.577– 6.752; P = 0.001) or severe CSVD burden (OR, 2.794; 95% CI, 1.342– 5.817; P = 0.006) was significantly associated with the risk of cognitive impairment. Correlation analyses revealed that SII levels were negatively associated with MMSE scores (rs = − 0.391, P < 0.001), and positively associated with the total CSVD burden score (rs = 0.361, P < 0.001). Moreover, SII was significantly related to the severity of the CSVD burden (OR, 2.674; 95% CI, 1.359– 5.263; P = 0.004). The multivariable-adjusted odds ratios (95% CI) in highest tertile versus lowest tertile of SII were 8.947 (3.315– 24.145) for cognitive impairment and 4.945 (2.063– 11.854) for severe CSVD burden, respectively. The effect of higher SII on cognitive impairment development was partly mediated by severe CSVD burden.Conclusion: Elevated SII is associated with severe CSVD burden and cognitive impairment. The mediating role of severe CSVD burden suggests that higher SII may contribute to cognitive impairment through aggravating CSVD burden.Keywords: systemic immune-inflammation index, inflammation, cognitive impairment, cerebral small vessel disease, total burden

Aim: The factors driving microbial community β-diversity (variation in composition) at different spatial scales yield fundamental insights into the mechanisms that maintain ecosystem biodiversity, which as yet are uncertain. Here, we explore whether spatial scale-dependent patterns of β-diversity vary between microbial functional groups and bacterial taxa (i.e., diazotrophic and bacterial communities) across local to regional scales (from metres to hundreds of kilometres). Location: Eastern China. Time period: October and November 2015. Major taxa studied: Diazotrophic and bacterial communities. Methods We use two complementary statistical tools to unveil biotic mechanisms (i.e., species association) underlying variation in β-diversity of diazotrophic and bacterial communities. We examined distance–decay slopes of both communities at the local (1–113 m), meso- (3.4–39 km) and regional (103–668 km) scales. We used an environmentally constrained checkerboard score and topological features of association networks as indices of species association. We then calculated contributions of species association, abiotic factors and geographical distance to explain community β-diversity. The scale-dependent distance–decay relationships were also examined in ubiquitous (high occupancy across samples) and endemic communities of diazotrophs and bacteria. Results Diazotrophs displayed steeper distance–decay slopes than bacteria, suggesting that the β-diversity of diazotrophic communities was more variable. The distance–decay slopes were dependent on spatial scales in both communities, owing to different contributions of geographical distance, abiotic factors and species association at three spatial scales. Intriguingly, species association was greater and contributed more to community β-diversity than other forces at the local scale, implying that species association could greatly alter community structures. Main conclusions Drivers of diazotrophic and bacterial community β-diversity depended on spatial scales, resulting in different distance–decay patterns. Moreover, this was the first study to use two methods to demonstrate that species association played important, but as yet unrecognized, roles in driving spatial scale-dependent β-diversity.

Brandilyn A Peters,1 Nanette Santoro,2 Robert C Kaplan,1,3 Qibin Qi1 1Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA; 2Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO, USA; 3Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USACorrespondence: Brandilyn A Peters, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, #1315AB, Bronx, NY, 10461, USA, Tel +1-718-430-3281, Email Brandilyn.Peterssamuelson@einsteinmed.orgAbstract: The gut microbiome is an important contributor to human health, shaped by many endogenous and exogenous factors. The gut microbiome displays sexual dimorphism, suggesting influence of sex hormones, and also has been shown to change with aging. Yet, little is known regarding the influence of menopause – a pivotal event of reproductive aging in women – on the gut microbiome. Here, we summarize what is known regarding the interrelationships of female sex hormones and the gut microbiome, and review the available literature on menopause, female sex hormones, and the gut microbiome in humans. Taken together, research suggests that menopause is associated with lower gut microbiome diversity and a shift toward greater similarity to the male gut microbiome, however more research is needed in large study populations to identify replicable patterns in taxa impacted by menopause. Many gaps in knowledge remain, including the role the gut microbiome may play in menopause-related disease risks, and whether menopausal hormone therapy modifies menopause-related change in the gut microbiome. Given the modifiable nature of the gut microbiome, better understanding of its role in menopause-related health will be critical to identify novel opportunities for improvement of peri- and post-menopausal health and well-being.Keywords: menopause, gut microbiome, estrobolome, microbial translocation, estrogen, progesterone

Shaobo Duan,1 Ye Zhang,1 Shuang Xu,1 Pei Jiang,1 Qinghua Qi2 1Department of Health Management, Henan Provincial People’s Hospital Zhengzhou University People’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Qinghua Qi, Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China, Email qiqinghua333@sina.comObjective: To investigate the predictive role of contrast-enhanced ultrasonography (CEUS) plus D-dimer levels in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL).Methods: CEUS was applied to assess lymph nodes in 186 patients with confirmed DLBCL. The clinical data and laboratory indicators were collected from these patients, and a retrospective analysis was conducted on the relationship between the quantitative parameters of CEUS (TTP, PI, AUC, WOT), D-dimer levels, and clinical features of the DLBCL patients. The Cox regression model was used for univariate and multivariate analyses for the risk factors associated with the prognosis.Results: There was an increase of D-dimer levels in advanced DLBCL patients, who were combined with a significant reduction in TTP and WOT and a significant increase in PI and AUC. D-dimer levels and quantitative parameters of CEUS were strongly correlated with the Ann Arbor, B symptoms, International Prognostic Index (IPI), LDH and CRP levels. The results of the Cox regression model indicated that D-dimer levels, TTP and PI, the quantitative parameters of CEUS, were important prognostic factors for DLBCL.Conclusion: CEUS results and D-dimer levels can be used as independent prognostic factors for DLBCL.Keywords: diffuse large B-cell lymphoma, contrast-enhanced ultrasonography, D-dimer, prognosis

Wenqing Gao,1,&ast; Yuanyuan Li,1,&ast; Teng Zhang,1 Jianglong Lu,2 Jiasong Pan,1 Qi Qi,1 Siqi Dong,3 Xiangjun Chen,3,4 Zhipeng Su,2 Jixi Li1,4 1State Key Laboratory of Genetic Engineering, Department of Neurology, Huashan Hospital and Institute of Neurology, School of Life Sciences, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, Shanghai, 200438, People’s Republic of China; 2Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 3Department of Neurology, Huashan Hospital and Institute of Neurology, Fudan University, Shanghai, 200040, People’s Republic of China; 4National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhipeng Su; Jixi Li, Email drsuzhipeng@wmu.edu.cn; lijixi@fudan.edu.cnBackground: Glioblastoma (GBM) is the most common and aggressive brain tumor in adults, in which chemokines are often upregulated and may play pivotal roles in their development and progression. Chemokines are a large subfamily of cytokines with leukocyte chemotactic activities involved in various tumor progression. However, gene expression patterns of the chemokines on a global scale were not known in GBM.Methods: Differentially expressed chemokine genes in glioma and normal samples were screened by using The Cancer Genome Atlas (TCGA) database. Cox regression identified the prognosis-related genes in each glioma subtype. The protein expression levels of chemokines in 72 glioma tissues were detected by ELISA.Results: We found that the transcripts of seven chemokines, including CCL2, CCL8, CCL18, CCL28, CXCL1, CXCL5, and CXCL13, were highly expressed in GBM that evidenced by involving immune cell infiltration regulation and accompanied with worse outcomes of GBM patients. The prognostic nomogram construction demonstrated that CCL18 held the highest risk score in patients with GBM. Furthermore, experiments on 72 glioma tissue samples confirmed that CCL18 protein expression was positively associated with tumor grade and IDH1 status but inversely with glioma patients’ overall survival (OS).Conclusion: Our study reveals comprehensive and comparable roles of chemokine members in glioblastoma, and identified CCL18 as a critical driver of GBM malignant behaviors, therefore providing a potential target for developing prognosis and therapy in human glioblastoma.Keywords: chemokines, GBM, biomarker, overall survival, prognosis

Qingqing Qi,1 Qingxu Song,2 Yufeng Cheng,2 Nana Wang2 1Department of Gastroenterology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Department of Radiation Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Nana WangDepartment of Radiation Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaEmail wangna03@163.comBackground: Prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) are the most common factors to estimate nutritional and inflammatory status. The aim of this study is to systematically evaluate the prognostic significance of above nutritional and inflammatory indexes for overall survival (OS) and surgical complications in esophageal cancer patients.Methods: Esophageal cancer patients who underwent esophagectomy were retrospectively collected. PNI, NLR, PLR, and SII were introduced to evaluate the baseline nutritional and inflammatory status.Results: A total of 407 patients were included in the present study. Kaplan–Meier survival analysis revealed that PNI-low group, NLR-high group and PLR-high group, all showed a significantly shorter OS (34.38% vs 49.46%, P < 0.001; 36.13% vs 48.26%, P = 0.026 and 33.33% vs 48.52%, P = 0.001 respectively), while no significant difference was found in SII groups (42.33% vs 46.31%, P = 0.067). Multivariable analyses identified PNI (P = 0.002) was an independent prognostic factor for OS, but NLR (P = 0.672) and PLR (P = 0.186) were not. Postoperative complications occurred significantly more frequently in the low-PNI group (29.69% vs 13.26%, P < 0.001). However, no significant differences were found in the postoperative complication rates between different NLR (16.67% vs 22.69%, P = 0.124), PLR (18.03% vs 19.61%, P = 0.867) and SII (15.34% vs 20.49%, P = 0.326) groups. Multivariate logistic regression analysis showed only PNI (P = 0.008) was an independent prognostic factor for postoperative complications.Conclusion: Preoperative low PNI was not only an independent prognostic factor for worse survival in esophageal cancer patients but also associated with high incidence of postoperative complications.Keywords: esophageal cancer, prognostic nutritional index, prognosis, postoperative complications

Qi Qi,* Xuemeng Qian,* Xinfang Zhu, Jiajing Cai, Rong Xia, Qi Zhang Department of Transfusion Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rong Xia; Qi ZhangDepartment of Transfusion Medicine, Huashan Hospital, Fudan University, 12 Urumqi Middle Road, Shanghai, 200040, People’s Republic of ChinaEmail xiarongcn@126.com; friday0451@163.comPurpose: Blood loss may be corrected with red blood cell transfusion, but may ultimately contribute to negative impacts. This study was a retrospective analysis to assess the impact of perioperative blood transfusion on hospital stay days in liver cancer patients.Methods: We retrospectively examined data from patients with primary liver cancer who underwent curative resection. Patients were divided into perioperative blood transfusion (PBT) and non-PBT groups. Data were given as means and SDs for continuous variables and as counts and percentage for categorical variables. The correlation between blood transfusion and hospital stay days was analyzed by Fisher’s exact test. Multivariable logistic regression analyses were used to identify independent predictors of length of hospital stays.Results: Totally 206/1031 patients (20.3%) were given perioperative transfusion. The mean length of hospital stay was 17.8 days in PBT and 13.9 days in non-PBT groups. Our multivariable logistic regression showed transfusion, total bilirubin, indirect bilirubin, and the ratio of albumin to bilirubin were all indicators of the length of hospital stay days. Perioperative transfusion was also associated with prolonged length of hospital stays (95% CI: 0.395– 0.811, p = 0.002). Transfusion also affected intrinsic coagulation factors (activated partial thromboplastin time, fibrinogen, platelet), inflammatory index (neutrocyte to lymphocyte ratio, monocyte), albumin and bilirubin levels.Conclusion: Perioperative transfusion of blood was associated with a significantly increased length of hospital stays probably via changing intrinsic coagulation and inflammatory factors and bilirubin levels in plasma.Keywords: primary liver cancer, transfusion, length of hospital stays, bilirubin, coagulation factor, inflammatory factor

Objectives: The identification of structural variants and single‐nucleotide variants is essential in finding molecular etiologies of monogenic genetic disorders. Whole‐genome sequencing (WGS) is becoming more widespread in genetic disease diagnosis. However, data on its clinical utility remain limited in prenatal practice. We aimed to expand our understanding of implementing WGS in the genetic diagnosis of fetal structural anomalies. Methods: We employed trio WGS with a minimum coverage of 40× on the MGI DNBSEQ‐T7 platform in a cohort of 17 fetuses presenting with aberrations detected by ultrasound, but uninformative findings of standard chromosomal microarray analysis (CMA) and exome sequencing (ES). Results: Causative genetic variants were identified in two families, with an increased diagnostic yield of 11.8% (2/17). Both were exon‐level copy‐number variants of small size (3.03 kb and 5.16 kb) and beyond the detection thresholds of CMA and ES. Moreover, to the best of our knowledge, we have described the first prenatal instance of the association of FGF8 with holoprosencephaly and facial deformities. Conclusions: Our analysis demonstrates the clinical value of WGS in the diagnosis of the underlying etiology of fetuses with structural abnormalities, when routine genetic tests have failed to provide a diagnosis. Additionally, the novel variants and new fetal manifestations have expanded the mutational and phenotypic spectrums of BBS9 and FGF8. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Abstract Objective The present study aimed to preliminary explore the abnormal neuromagnetic activation in female migraine patients between attacks using magnetoencephalography (MEG) and pattern reversed visual evoked magnetic fields (PR-VEFs). Methods A total of 17 female migraine subjects during the headache-free phase and 17 healthy controls (HC) were studied using a 275-channel magnetoencephalography (MEG) system. In this study, visual evoked magnetic fields (VEFs) were generated by a pattern-reversal check as the visual stimulus. The average of 100 VEFs was evolved by different half patterns were averaged and used to analyze waveform, spectrum, and source location within two frequency ranges (5–100 and 100–1000 Hz), respectively. Results In migraine subjects, the latency of second peak of VEFs (VIIs) showed significant prolongations when compared with HC. On the sensor level, the cortical spectral power in migraine subjects was similar to that of HC in the 5–100 Hz range and was lower in the 1000–1000 Hz range. There was a decrement of source strength in the visual cortex in migraine patients when compared to HC in both the 5–100 and 100–1000 Hz frequency range. Moreover, there was a similar odds of activation in 5–100 and 100–1000 Hz frequency ranges in the area beyond the primary visual cortex between the two groups. In addition, no correlation was observed between clinical data (intensity of headache, headache-history duration, the frequency of headaches) and MEG results. Conclusions The findings presented in the current study, suggested that interictal cortical activation following a visual stimulus was low in female migraine patients. The low pre-activation was detected in the visual cortex using VEF and MEG in both low and high-frequency band. Our results add to the existing evidence that cortical interictal excitability change may be relative to the pain-module mechanism in migraine brains. Thus, our data improved the apprehension of the cortical disorder of migraine in the high-frequency domain.

Xi Yang,1 Miao Da,2 Wenyuan Zhang,3 Quan Qi,4 Chun Zhang,5 Shuwen Han4 1Department of Intervention and Radiotherapy, Huzhou Central Hospital, 2Medical College of Nursing, Huzhou University, 3Department of Gynaecology, 4Department of Medical Oncology, 5Department of Infectious Diseases, Huzhou Central Hospital, Huzhou, Zhejiang Province, People’s Republic of China Abstract: Cervical cancer is a common malignant cancer among women worldwide. Changes in the vaginal microecological environment lead to multiple gynecological diseases, including cervical cancer. Recent research has shown that Lactobacillus may play an important role in the occurrence and development of cervical cancer. This review explores the role of Lactobacillus in cervical cancer. A total of 29 articles were included after identification and screening. The pertinent literature on Lactobacillus in cervical cancer from two perspectives, including clinical studies and experimental studies, was analyzed. An association network for the mechanism by which Lactobacillus induces cervical cancer was constructed. In addition, we provide direction and insight for further research on the role of Lactobacillus in cervical cancer. Keywords: CIN, cervical cancer, Lactobacillus, microorganism

Quan Qi,1,* Lei Lu,2,3,* Haiqing Li,1,* Zhize Yuan,1 Gaoxian Chen,2,3 Miao Lin,2,3 Zhengwen Ruan,4 Xiaofeng Ye,1 Zeyu Xiao,2,3,5 Qiang Zhao1 1Department of Cardiac Surgery, Rui Jin Hospital, 2Department of Pharmacology, Institute of Medical Sciences, 3Translational Medicine Collaborative Innovation Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 4Department of Cardiology, Yuyao People’s Hospital, Yuyao, Zhejiang, 5Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: The local, intramyocardial injection of proteins into the infarcted heart is an attractive option to initiate cardiac regeneration after myocardial infarction (MI). Liraglutide, which was developed as a treatment for type 2 diabetes, has been implicated as one of the most promising protein candidates in cardiac regeneration. A significant challenge to the therapeutic use of this protein is its short half-life in vivo. In this study, we evaluated the therapeutic effects and long-term retention of liraglutide loaded in poly(lactic-co-glycolic acid)–poly(ethylene glycol) (PLGA–PEG) nanoparticles (NP-liraglutide) on experimental MI. PLGA–PEG nanoparticles (NPs) have been shown to efficiently load liraglutide and release bioactive liraglutide in a sustained manner. For in vitro test, the released liraglutide retained bioactivity, as measured by its ability to activate liraglutide signaling pathways. Next, we compared the effects of an intramyocardial injection of saline, empty NPs, free liraglutide and NP-liraglutide in a rat model of MI. NPs were detected in the myocardium for up to 4 weeks. More importantly, an intramyocardial injection of NP-liraglutide was sufficient to improve cardiac function (P

Qi Qi,1,2 Yuxin Zhang,1 Lin Shen,1 Rui Wang,1 Jiansheng Zhou,1 Hezuo Lü,1,3 Jianguo Hu1,3 1Anhui Key Laboratory of Tissue Transplantation, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People’s Republic of China; 2Department of Histology and Embryology, Bengbu Medical College, Bengbu, Anhui, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, People’s Republic of China Purpose: Our purpose was to systematically investigate the expression pattern and role of Olig1 in neural cells during rat spinal cord development.Animals and methods: Spinal cord tissues were dissected from Sprague–Dawley rats at embryonic day 14.5 (E14.5) and E18.5, postnatal day 0 (P0), P3, P7, postnatal 2 weeks (P2W), P4W, and adults (more than 2 months after birth), respectively. The expression of Olig1 was determined by Western blot and immunostaining. To observe expression of Olig1 in different neural cell types, a double immunohistochemical staining was performed using antibodies against Olig1 with O4, ß-tubulin, glial fibrillary acidic protein (GFAP), and myelin basic protein, respectively.Results: The expression of Olig1 protein shows a significant level change in rat spinal cord at different developmental time points. Starting with E14.5, the expression gradually increased and peaked at E18.5. Olig1 decreased gradually from P3 and reached its lowest level on P7. However, interestingly, the Olig1 expression increased again from P2W, until adulthood. Olig1 was coexpressed with O4-positive oligodendrocyte progenitor cells (OPCs) and β-tubulin-positive neurons at all time points during development. Olig1 was also coexpressed transiently with GFAP-positive astrocytes at only E14.5. Olig1 was localized in the cytoplasm of O4- and β-tubulin-positive cells during the period from E14.5 to adult.Conclusion: The expression of Olig1 in OPCs and neurons at all time points during development and in astrocytes at E14.5 suggests that Olig1 may play an important role in the generation and maturation of specific neural cells during development of spinal cord. Our results contribute to understanding the mechanism underlying developmental regulation of neural cells by Olig1. Keywords: Olig1, spinal cord, development, neural cells

We isolated 65 rhizobial strains from faba bean (Vicia faba L.) from Panxi, China, studied their plant growth promoting ability with nitrogen free hydroponics, genetic diversity with clustered analysis of combined ARDRA and IGS-RFLP, and phylogeny by sequence analyses of 16S rRNA gene, three housekeeping genes and symbiosis related genes. Eleven strains improved the plant shoot dry mass significantly comparing to that of not inoculated plants. According to the clustered analysis of combined ARDRA and IGS-RFLP the isolates were genetically diverse. Forty-one of 65 isolates represented Rhizobium anhuiense, and the others belonged to R. fabae, Rhizobium vallis, Rhizobium sophorae, Agrobacterium radiobacter, and four species related to Rhizobium and Agrobacterium. The isolates carried four and five genotypes of nifH and nodC, respectively, in six different nifH-nodC combinations. When looking at the species-nifH-nodC combinations it is noteworthy that all but two of the six R. anhuiense isolates were different. Our results suggested that faba bean rhizobia in Panxi are diverse at species, plant growth promoting ability and symbiosis related gene levels.

Tao Liu,1 Shenglin Luo,1 Yang Wang,1 Xu Tan,1 Qingrong Qi,2 Chunmeng Shi1 1Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, People's Republic of China; 2Key Laboratory of Drug-Targeting and Drug-Delivery Systems of the Ministry of Education, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu, People's Republic of China Abstract: Near-infrared (NIR) fluorescent sensors have emerged as promising molecular tools for cancer imaging and detection in living systems. However, cancer NIR fluorescent sensors are very challenging to develop because they are required to exhibit good specificity and low toxicity as an eligible contrast agent. Here, we describe the synthesis of a new heptamethine indocyanine dye (NIR-27) modified with a glycine at the end of each N-alkyl side chain, and its biological characterization for in vivo cancer-targeted NIR imaging. In addition to its high specificity, NIR-27 also shows lower cytotoxicity than indocyanine green, a nonspecific NIR probe widely used in clinic. These characteristics suggest that NIR-27 is a promising prospect as a new NIR fluorescent sensor for sensitive cancer detection. Keywords: near-infrared (NIR), heptamethine dye, cancer-targeted imaging