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Jiong Li,1 Dongqin Lei,1 Yanbing Cao,2,3 Fuli Xin,2,3 Zhenxi Zhang,1 Xiaolong Liu,2,3 Ming Wu,2,3 Cuiping Yao1 1Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Biomedical Photonics and Sensing, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China; 2The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People’s Republic of China; 3Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, People’s Republic of ChinaCorrespondence: Ming Wu, Mengchao Hepatobiliary Hospital of Fujian Medical University, 312 Xi Hong Road, Fuzhou, 350025, People’s Republic of China, Email wmmj0419@163.com Cuiping Yao, School of Life Science and Technology, Xi’an Jiaotong University, 28 Xian Ning West Road, Xi’an, 710049, People’s Republic of China, Email zsycp@xjtu.edu.cnIntroduction: Photodynamic therapy (PDT) has attracted increasing attention in the clinical treatment of epidermal and luminal tumors. However, the PDT efficacy in practice is severely impeded by tumor hypoxia and the adverse factors associated with hydrophobic photosensitizers (PSs), including low delivery capacity, poor photoactivity and limited ROS diffusion. In this study, Pt nanozymes decorated two-dimensional (2D) porphyrin metal-organic framework (MOF) nanosheets (PMOF@HA) were fabricated and investigated to conquer the obstacles of PDT against hypoxic tumors.Materials and Methods: PMOF@HA was synthesized by the coordination of transition metal iron (Zr4+) and PS (TCPP), in situ generation of Pt nanozyme and surface modification with hyaluronic acid (HA). The abilities of hypoxic relief and ROS generation were evaluated by detecting the changes of O2 and 1O2 concentration. The cellular uptake was investigated using flow cytometry and confocal laser scanning microscopy. The SMMC-7721 cells and the subcutaneous tumor-bearing mice were used to demonstrate the PDT efficacy of PMOF@HA in vitro and in vivo, respectively.Results: Benefiting from the 2D structure and inherent properties of MOF materials, the prepared PMOF@HA could not only serve as nano-PS with high PS loading but also ensure the rational distance between PS molecules to avoid aggregation-induced quenching, enhance the photosensitive activity and promote the rapid diffusion of generated radical oxide species (ROS). Meanwhile, Pt nanozymes with catalase-like activity effectively catalyzed intratumoral overproduced H2O2 into O2 to alleviate tumor hypoxia. Additionally, PMOF@HA, with the help of externally coated HA, significantly improved the stability and increased the cell uptake by CD44 overexpressed tumor cells to strengthen O2 self-supply and PDT efficacy.Conclusion: This study provided a new strategy of integrating 2D porphyrin MOF nanosheets with nanozymes to conquer the obstacles of PDT against hypoxic tumors.Keywords: 2D porphyrin MOF, hypoxic relief, Pt nanozyme, photodynamic therapy

Xinyan Ma,1,2,* Ziyan Wu,1,2,* Junpeng Li,1,2 Yang Yang1,2 1College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, People’s Republic of China; 2Jiangsu Co-Innovation Center for Important Animal Infectious Diseases and Zoonoses, and Joint Laboratory of International Cooperation on Prevention and Control Technology of Important Animal Diseases and Zoonoses of Jiangsu Higher Education Institutions, Yangzhou, 225009, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang Yang, Email YangyangYZU@163.comPurpose: Biofilms significantly contribute to the persistence and antibiotic resistance of Staphylococcus aureus infections. However, the regulatory mechanisms governing biofilm formation of S. aureus remain not fully elucidated. This study aimed to investigate the function of the S. aureus lineage-specific two-component system, desKR, in biofilm regulation and pathogenicity.Methods: Bioinformatic analysis was conducted to assess the prevalence of desKR across various S. aureus lineages and to examine its structural features. The impact of desKR on S. aureus pathogenicity was evaluated using in vivo mouse models, including skin abscess, bloodstream infection, and nasal colonization models. Crystal violet staining and confocal laser scanning microscopy were utilized to examine the impact of desKR on S. aureus biofilm formation. Mechanistic insights into desKR-mediated biofilm regulation were investigated by quantifying polysaccharide intercellular adhesin (PIA) production, extracellular DNA (eDNA) release, autolysis assays, and RT-qPCR.Results: The prevalence of desKR varied among different S. aureus lineages, with notably low carriage rates in ST398 and ST59 lineages. Deletion of desKR in NCTC8325 strain resulted in decreased susceptibility to β-lactam and glycopeptide antibiotics. Although desKR did not significantly affect acute pathogenicity, the ΔdesKR mutant exhibited significantly reduced nasal colonization and biofilm-forming ability. Overexpression of desKR in naturally desKR-lacking strains (ST398 and ST59) enhanced biofilm formation, suggesting a lineage-independent effect. Phenotypic assays further revealed that the ΔdesKR mutant showed reduced PIA production, decreased eDNA release, and lower autolysis rates. RT-qPCR indicated significant downregulation of icaA, icaD, icaB, and icaC genes, along with upregulation of icaR, whereas autolysis-related genes remained unchanged.Conclusion: The desKR two-component system positively regulates S. aureus biofilm formation in a lineage-independent manner, primarily by modulating PIA synthesis via the ica operon. These findings provide new insights into the molecular mechanisms of biofilm formation in S. aureus and highlight desKR as a potential target for therapeutic strategies aimed at combating biofilm-associated infections.Keywords: Staphylococcus aureus, two-component system, desKR, biofilm

Aixiang Lv,1,2,* Jingmin Li,1,2,* Meihuan Chen,1,* Wei Wang,3 Liangpu Xu,1 Hailong Huang1,2 1Medical Genetic Diagnosis and Therapy Center of Fujian Maternity and Child Health Hospital, Fujian Provincial Key Laboratory for Prenatal Diagnosis and Birth Defect, Fuzhou, People’s Republic of China; 2College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Plastic Surgery, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liangpu Xu; Hailong Huang, Email xiliangpu@fjmu.edu.cn; huanghailong@fjmu.edu.cnPurpose: Thalassemia, an inherited quantitative globin disorder, is the most prevalent monogenic disease globally. While severe alpha thalassemia results in intrauterine death, β-thalassemia manifests during childhood due to the “second conversion of hemoglobin”, garnering increased attention in recent decades.Methods: In this study, a bibliometric analysis was conducted of thalassemia articles published in the Web of Science Core Collection database between 2013 and 2023 to establish a comprehensive overview and to identify emerging trends. A total of 5655 studies published between 2013 and 2023 were systematically retrieved, and annual publications demonstrated a steady increase, maintaining a high level over the past decade.Results: The United States contributed the highest number of publications, followed by China. Notably, the journal Blood emerged as the leading authority in β-thalassemia research. Analysis of research hotspots revealed that the pathogenesis of β-thalassemia is primarily linked to iron overload, anemia, gene mutations, and ineffective erythropoiesis. Furthermore, recent studies focusing on gene editing therapies present promising avenues for future investigation.Conclusion: These findings grasp the research status of β-thalassemia and shed new light on future research frontiers.Keywords: bibliometric, citespace, hotspots, thalassemia, VOSviewer

Qianhan Lin,1 Jiajia Li,1 Zulimire Abudousalamu,1 Yating Sun,1 Mengyang Xue,1 Liangqing Yao,2 Mo Chen1 1Department of Gynecologic Oncology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Gynecologic Oncology, Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Liangqing Yao; Mo Chen, Email yaoliangqing@163.com; chenmo_nicy@163.comAbstract: Ovarian cancer (OC) is the most lethal reproductive system cancer and a leading cause of cancer-related death. The high mortality rate and poor prognosis of OC are primarily due to its tendency for extensive abdominal metastasis, late diagnosis in advanced stages, an immunosuppressive tumor microenvironment, significant adverse reactions to first-line chemotherapy, and the development of chemoresistance. Current adjuvant chemotherapies face challenges such as poor targeting, low efficacy, and significant side effects. Targeted drug delivery systems (TDDSs) are designed to deliver drugs precisely to the tumor site to enhance efficacy and minimize side effects. This review highlights recent advancements in the use of TDDSs for OC therapies, including drug conjugate delivery systems, nanoparticle drug delivery systems, and hydrogel drug delivery systems. The focus is on employing TDDS to conduct direct, effective, and safer interventions in OC through methods such as targeted tumor recognition and controlled drug release, either independently or in combination. This review also discusses the prospects and challenges for further development of TDDSs. Undoubtedly, the use of TDDSs shows promise in the battle against OCs.Keywords: targeted drug delivery, ovarian cancer, drug conjugates, nanoparticle, hydrogel

Qingbao Guo,1,2,* Manli Xie,3,* Qian-Nan Wang,4,* Jingjie Li,1,2 Simeng Liu,1,2 Xiaopeng Wang,1,2 Dan Yu,5 Zhengxing Zou,5 Gan Gao,1,2 Qian Zhang,5 Fangbin Hao,1,2 Jie Feng,5 Rimiao Yang,5 Minjie Wang,1,2 Heguan Fu,5 Xiangyang Bao,5 Lian Duan2 1Medical School of Chinese PLA, Beijing, People’s Republic of China; 2Department of Neurosurgery, First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Occupational Diseases, Xi’an Central Hospital, Xi’an, Shanxi, People’s Republic of China; 4Department of Neurosurgery, Eighth Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 5Department of Neurosurgery, Fifth Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangyang Bao; Lian Duan, Email bzy123@163.com; duanlian307@sina.comBackground: Moyamoya disease (MMD) signifies a cerebrovascular disorder with obscure origin and a more rapid and severe progression in children than adults. This investigation aims to uncover age-associated distinctions through proteomic and metabolomic profiling to gain insights into the underlying mechanisms of MMD.Methods: Twelve MMD patients—six children and six adults—along with six healthy controls (HC), participated, each providing a 10 mL blood sample. Serum proteomic and metabolomic analyses were conducted using ultra-performance liquid chromatography and high-resolution mass spectrometry, complemented by bioinformatics to identify differential biomolecules and their interactions. Pathway implications were ascertained using GO and KEGG enrichment analysis.Results: Notable proteomic and metabolomic discrepancies were observed between pediatric and adult MMD subjects. A total of 235 and 216 proteins varied in adult and pediatric cases compared to HCs, with 73 proteins shared. In addition, 129 and 74 anionic, plus 96 and 104 cationic metabolites, were differentially expressed in the pediatric and adult groups, respectively, with 34 anionic and 28 cationic metabolites in common. Age-specific biomolecules further characterized these distinctions. Enrichment analysis pinpointed immunity and inflammation pathways, with vitamin digestion and absorption highlighted as pivotal in pediatric MMD.Conclusion: This study unveils distinct metabolic and proteomic patterns within pediatric and adult MMD patients. The critical role of the vitamin digestion and absorption pathway in the pathogenesis of pediatric MMD offers novel insight into disease mechanisms. Keywords: proteomics, metabolomics, pediatric patients, moyamoya disease, integration analysis

Ruixi Li,1 Lulu Liu,1 Yong Liu,1 Jiang Tang,1 Jinsong Li2 1Yueyang Guangji Hospital, Yueyang, Hunan, People’s Republic of China; 2Department of Spine Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Jinsong Li, Department of Spine Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China, Tel +86-731-88618826, Fax +86-731-88618526, Email jinsongli_csu@163.comIntroduction: Protocadherin 9 (PCDH9), a member of the cadherin superfamily of transmembrane proteins, plays a role in cell adhesion and neural development. Recent studies suggest that PCDH9 may function as a tumor suppressor in certain cancers, though its specific role in breast cancer remains unclear.Methods: UALCAN database to retrieve information on PCDH9 expression in breast cancer tissues compared with that in normal tissues. The biological effects of PCDH9 in breast cancer cells were analyzed using the DepMap database. Stable knockdown or overexpression of PCDH9 in breast cancer cell lines and subsequently assessed tumor cell proliferation and migration. Synthetic lethal screening was conducted for breast cancer cells with low PCDH9 expression or deficiency.Results: In this study, we observed significant downregulation of PCDH9 in breast cancer tissues, with its expression negatively correlated with progression-free survival. Further investigations revealed that decreased PCDH9 expression promotes breast cancer cell proliferation and migration, while overexpression of PCDH9 has the opposite effect. Subsequently, we identified the TAS-102, an approved drug for metastatic colorectal cancer, exhibited selective cytotoxicity against breast cancer cells with low PCDH9 expression.Conclusion and discussion: In summary, our study identified PCDH9 as a tumor suppressor in breast cancer and highlighted TAS-102 as a potential therapeutic option for tumors with low PCDH9 expression or deficiency. The specific interaction between TAS-102 and PCDH9 warrants further exploration, providing deeper insights into its mode of action in treating PCDH9-deficient breast cancer.Keywords: breast cancer, PCDH9, synthetic lethality, TAS-102

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

Bo Xu,1 Xudong Zhao,2 Lei Zhang,1 Shouhan Feng,3 Jinxia Li,1 Ye Xu4 1Acupuncture and Rehabilitation Department, Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Huzhou, Zhejiang, People’s Republic of China; 2Physical Therapy Center, Huzhou Third Municipal Hospital, the Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, People’s Republic of China; 3Oncology Department, Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Huzhou, Zhejiang, People’s Republic of China; 4Rehabilitation Department, Huzhou Third Municipal Hospital, the Affiliated Hospital of Huzhou University, Huzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Ye Xu, Rehabilitation Department, Huzhou Third Municipal Hospital, the Affiliated Hospital of Huzhou University, No. 2088 Tiaoxi East Road, Huzhou City, Zhejiang Province, People’s Republic of China, Email 15268277775@163.comPurpose: Pain management for spinal facet joint (SFJ) and sacroiliac joint (SIJ) pain is challenging, often requiring interventions like radiofrequency ablation (RFA) or corticosteroid injections (CI). This study aims to assess and compare the effectiveness of CI and RFA in treating SFJ and SIJ pain. We combine these treatments due to their shared pathophysiology, similar therapeutic interventions, and the necessity for an integrated approach to spinal pain management.Patients and methods: Literature search from PubMed, Scopus, CENTRAL and Google Scholar for published studies upto 31st December 2023, and reporting data of patients who were treated using CI of RFA for SFJ and SIJ pain. Pooled standardized mean difference (SMD) with a 95% Confidence Interval (CI) was calculated.Results: Our meta-analysis incorporated thirteen studies. Overall, patients, treated with CI had a higher pain intensity score compared to patients treated with RFA (SMD=0.92; 95% CI: 0.19 to 1.65) at 3 months, and at 6 months (SMD=1.53; 95% CI: 0.66 to 2.40) after the treatment. No significant association was reported at 12 months (SMD=1.47; 95% CI: − 0.03 to 2.97). Subgroup analysis based on joint types revealed increased pain intensity scores in patients who were treated with CI for SIJ (SMD=1.25; 95% CI: 0.39 to 2.11) and SFJ (SMD=1.33; 95% CI: 0.09 to 2.57) pain. A negative but not significant effect was detected in patients, treated with CI for cervical joint pain (SMD=− 0.40; 95% CI: − 0.90 to 0.10). Patients treated with CI exhibited higher functional disability score compared to patients treated with RFA at 3 months (SMD=1.28; 95% CI: 0.20 to 2.35) post-treatment.Conclusion: This study suggests that RFA may offer superior pain relief with longer duration compared to steroid injections for spinal facet and sacroiliac joint pain. Decision regarding specific interventions should be individualized and consider patient preferences, clinical context, and potential risks.Keywords: radiofrequency ablation, steroid injections, spinal facet pain, sacroiliac joint pain, systematic review, meta-analysis, pain management

Fei Gao,1,&ast; Siqi He,1,&ast; Jing Li,1 Xiaoyue Wang,2 Xiaoting Chen,2 Xiaoning Bu1 1Department of Respiratory and Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoning Bu, Department of Respiratory and Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4th Ring Road West, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +8613641000837, Email 13641000837@163.comPurpose: Systemic Immune-Inflammation Index (SII), calculated by (neutrophils count × platelet count)/lymphocytes count, is a novel index of the local immune response and systemic inflammation response. The SII has been shown to play an important role in the prognosis of many diseases, including cardiovascular diseases, cancer and COPD. However, its role in the prognosis of bronchiectasis remains unclear and requires further investigation. This study aimed to investigate the association between SII and readmissions in patients with acute exacerbations of bronchiectasis.Patients and Methods: We conducted a retrospective cohort study of all bronchiectasis patients admitted to the respiratory ward in Beijing Chaoyang Hospital from January 2020 to January 2022. Patients were classified into four groups according to the quartiles of log2(SII) at admission. The primary endpoint was readmission at 1-year follow up. Univariate and multivariate cox regression models were applied to investigate the relationship between SII and readmissions at 1-year follow up in patients with bronchiectasis.Results: A total of 521 patients were included in our study. The median (IQR) SII at admission were 506.10 (564.84). Patients with higher SII tended to be older, male, past and current smokers, have lower BMI, and more dyspnea symptoms. They also had higher inflammatory markers and received a greater spectrum of antibiotics and more intravenous glucocorticoids. Higher SII at admission were independently associated with readmission in patients with acute exacerbations for bronchiectasis following confounder adjustment (OR =1.007; 95% CI, 1.003– 1.011; p < 0.001).Conclusion: Patients with elevated SII levels were typically older males, often smokers, with lower BMI and increased dyspnea. They received more antibiotics and intravenous glucocorticoids. Higher SII at admission are associated with readmission in patients with acute exacerbations of bronchiectasis. SII has potential clinical value as a predictive biomarker for clinical outcomes in bronchiectasis, offering a valuable tool for management strategies.Keywords: chronic respiratory disease, inflammation, prognosis

Bolin Zhu, Pengfei Jin, Jianchun Li, Yuanchao Zhu Department of Pharmacy, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Key Laboratory of Assessment of Clinical Drugs Risk and Individual Application (Beijing Hospital), Beijing, 100730, People’s Republic of ChinaCorrespondence: Yuanchao Zhu, Email yczhu-2009@163.comBackground: Drug-induced thrombocytopenia is a rare adverse reaction of drug therapy and usually underdiagnosed. Cefoperazone/sulbactam is a compound preparation composed of the third generation of cephalosporin and β-lactamase inhibitor, of which thrombocytopenia is an uncommon but serious adverse reaction. However, the existing literature on cefoperazone/sulbactam-induced thrombocytopenia remains limited, and the specific risk factors associated with this adverse effect have not been thoroughly elucidated. Consequently, this study aims to investigate the clinical characteristics and identify the risk factors for thrombocytopenia in adult patients undergoing cefoperazone/sulbactam therapy.Methods: In this retrospective study, we reviewed patients treated with cefoperazone/sulbactam at Beijing Hospital between January 2017 and June 2023. Patients were categorized into two groups based on the presence or absence of thrombocytopenia: the thrombocytopenia group and the non-thrombocytopenia group. We collected data on demographic features, clinical characteristics, laboratory parameters, treatments, and outcomes. Subsequently, univariate and multivariate logistic regression analyses were performed to identify potential risk factors for cefoperazone/sulbactam-induced thrombocytopenia.Results: In total, 6489 patients were included in this study, and 2.4% (155/6489) developed thrombocytopenia. The results of multivariate analysis showed that cefoperazone/sulbactam therapy duration (d) > 14, PLT (109/L) < 200, daily dose of cefoperazone/sulbactam (g) ≥ 6, TBil (μmoL/L) > 21, AST (U/L) > 35, and use of non-invasive ventilator were risk factors for cefoperazone/sulbactam-induced thrombocytopenia.Conclusion: Despite the low incidence (2.4%), cefoperazone/sulbactam could cause serious thrombocytopenia sometimes accompanied with hemorrhage. In clinical therapy, clinicians should be vigilant in monitoring platelet count, especially for patients with risk factors of cefoperazone/sulbactam-induced thrombocytopenia.Keywords: cefoperazone/sulbactam, risk factor, thrombocytopenia, real-world study, logistic regression analysis

Yao Qin,1 Xingwu Zou,1 Yanghui Jin,2 Jinmeng Li,3 Qingshan Cai1 1Department of Tuberculosis, Hangzhou Red Cross Hospital, Hangzhou, People’s Republic of China; 2Department of Orthopaedic, Hangzhou Red Cross Hospital, Hangzhou, People’s Republic of China; 3Department of Pharmacy, Hangzhou Red Cross Hospital, Hangzhou, People’s Republic of ChinaCorrespondence: Qingshan Cai, Department of Tuberculosis, Hangzhou Red Cross Hospital, Hangzhou, People’s Republic of China, Email caiqs66@163.comAim: Cryptococcus neoformans osteomyelitis coupled with tuberculosis and tuberculous lymphadenitis, is a rare occurrence in clinical. Diagnostic challenges arise due to the clinical radiological similarity of this condition to other lung infections and the limited and sensitive nature of traditional approaches. Here, we present a case of co-infection diagnosed using Metagenomic Next-Generation Sequencing, highlighting the effectiveness of advanced genomic techniques in such complex scenarios.Case Presentation: We present a case of a 67-year-old female infected with cryptococcal osteomyelitis and presented with swelling and pain in the right ankle. Following a biopsy of the right ankle joint, Metagenomic Next-Generation Sequencing (mNGS) of the biopsy tissue revealed Cryptococcus neoformans infection. Positive results for Cryptococcus capsular antigen and pathological findings confirmed the presence of Cryptococcus neoformans. The patient underwent surgical debridement, coupled with oral fluconazole treatment (300mg/day), leading to the resolution of symptoms.Conclusion: Cryptococcus neoformans is an uncommon cause of ankle infection. Metagenomic Next-Generation Sequencing (mNGS) serves as a valuable diagnostic tool, aiding clinicians in differentiating cryptococcal osteomyelitis from other atypical infections.Keywords: Cryptococcus neoformans, tuberculosis, diagnosis, metagenomic next-generation sequencing, mNGS

Changjin Wang,1,&ast; Bangyuan Yang,1,&ast; Songyuan Luo,1 Shengneng Zheng,2 Yinghao Sun,1 Jiaohua Chen,1 Ruixin Fan,3 Jianfang Luo,1,&ast; Jie Li1,&ast; 1Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Radiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Cardiac Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Li; Jianfang Luo, Email leomoku1981@163.com; jianfangluo@sina.comBackground: The relationship between pulmonary hypertension (PH) and outcomes after transcatheter aortic valve replacement (TAVR) has been shown to be unfavorable. The impact of gender on TAVR outcomes remains controversial. There have been no studies evaluating the simultaneous effects of both factors on TAVR outcomes.Methods: We retrospectively analyzed a prospective cohort of patients who underwent TAVR between January 2016 and December 2022. The patients were stratified by gender and the presence of PH. The primary outcome of the study was all-cause mortality. Secondary outcome was a composite of all-cause mortality and heart failure hospitalization.Results: We identified a total of 133 female patients without PH, 179 males without PH, 87 females with PH, and 122 males with PH. The median follow-up period was 18 months. Female patients without PH demonstrated a lower cumulative mortality rate compared to those with male gender and/or PH. Adjusted multivariate Cox proportional hazard analyses revealed that male gender and PH status, either individually or in combination, were independently associated with long-term mortality when compared to female patients without PH. Specifically, females with PH (HR 6.80, 95% confidence interval (CI): 1.49– 31.12, P=0.013), males without PH (HR 6.45, 95% CI: 1.47– 28.22, P=0.013), and males with PH (HR 7.2, 95% CI: 1.63– 31.81, P=0.009) demonstrated significantly higher risk for mortality.Conclusion: Patients who were male or had PH status had a higher risk of mortality. However, there was no synergistic effect between being male and having PH on the prognosis after TAVR.Keywords: transcatheter aortic valve replacement, gender, pulmonary hypertension, outcome

Yan Wu,1 Zhenzhen Xu,2 Jing Dong,3 Wenzhong Zhang,2 Jing Li,2 Hong Ji1 1Department of Nursing, The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital), Jinan, Shandong, 250014, People’s Republic of China; 2School of Nursing, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, 250014, People’s Republic of China; 3School of Nursing, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, Shandong Province, 271016, People’s Republic of ChinaCorrespondence: Hong Ji, Department of Nursing, The First Affiliated Hospital of Shandong First Medical University (Shandong Provincial Qianfoshan Hospital), Jinan, Shandong, 250014, People’s Republic of China, Tel +86-13791120369, Email honghongji-2005@163.comBackground: Older age and female sex are risk factors for osteoarthritis and osteoporosis (OP). This study evaluated the knowledge, attitudes, and practices of patients with knee osteoarthritis (KOA) in China regarding OP and its prevention. This cross-sectional, questionnaire-based study enrolled patients with KOA at four grade-A tertiary hospitals in Shandong Province between 1st September and 20th November 2022.Methods: The administered questionnaire contained 55 items across four dimensions (demographic information, knowledge, attitude, and practice). Logistic regression analyses were performed to identify factors associated with an overall questionnaire score ≥ 70% of the maximum possible score. SPSS 26.0 was used for the analyses; P< 0.05 was considered significant.Results: The analysis included 434 participants (261 females). The median knowledge, attitude, and practice scores were 7 (interquartile range: 5– 10) (possible range, 0– 17 points), 44 (interquartile range: 42– 49) (possible range, 11– 55 points), and 43 (interquartile range: 38– 47) (possible range, 13– 65 points), respectively. Multivariable logistic regression indicated that female sex (odds ratio [OR], 2.421; 95% confidence interval [95% CI] 1.558– 3.762; P< 0.001), age 56– 65 years-old (OR, 4.222; 95% CI, 1.763– 10.109; P=0.001 vs ≤ 55 years-old), age > 65 years-old (OR, 4.358; 95% CI, 1.863– 10.195; P=0.001 vs ≤ 55 years-old), middle/high/technical secondary school education (OR, 1.853; 95% CI, 1.002– 3.428; P=0.049 vs primary school or below), and having KOA for 4– 5 years (OR, 2.682; 95% CI, 1.412– 5.094; P=0.003 vs ≤ 3 years) were independently associated with a high KAP score.Conclusion: There is room for improvement in the knowledge and practices of patients with osteoarthritis in China regarding OP. The findings of this study may facilitate the design and implementation of education programs to increase awareness about OP prevention among patients with KOA.Keywords: osteoarthritis of the knee, osteoporosis, disease prevention, surveys and questionnaires, health knowledge, attitudes, practice

Juan Li,1,&ast; Shu Wang,2,&ast; Chaoping Ma,1,&ast; Ning Ning,3,&ast; Yingying Huang,1,4,&ast; Min Jiao,1 Jiyuan Zhang,1 Wenwu Sun,3 Jiaoyan Li,3 Bing Zhao,3 Enqiang Mao,3 Zaiqian Che,3 Chengjin Gao1 1Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Intensive Care Medicine, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing, 400016, People’s Republic of China; 3Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China; 4Dementia Research Center, Macquarie University, Sydney, Australia&ast;These authors contributed equally to this workCorrespondence: Chengjin Gao, Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Shanghai, People’s Republic of China, Email gaochengjin@xinhuamed.com.cn Zaiqian Che, Departments of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China, Email chezaiqian@163.comPurpose: New-onset atrial fibrillation (NOAF) and sepsis-induced coagulopathy (SIC) are severe complications in septic patients. However, the relationship between NOAF and SIC score has not been clearly defined. This study aims to investigate the association between SIC score and NOAF, as well as their effect on mortality in sepsis.Patients and Methods: This study was a two-center retrospective analysis. Medical data were collected from patients diagnosed with sepsis. The patients were divided into NOAF and non-NOAF groups, and the SIC score was calculated for each group. Univariable and multivariable logistic regression analyses were performed to explore the relationship between the SIC score and NOAF, as well as their effects on mortality. The Kaplan-Meier curve was used to assess the survival rate.Results: A total of 2,280 septic patients were included, with 132 (5.7%) suffering from NOAF. Multivariable logistic regression analyses indicated that age, gender, the Acute Physiology and Chronic Health Evaluation II score (APACHE II), heart rate, renal failure, stroke, chronic obstructive pulmonary disease (COPD), and the SIC score were independent risk factors for NOAF in sepsis. Moreover, NOAF was associated with an increased risk of in-hospital mortality, 28-day mortality, and 90-day mortality. These results were consistent across subgroup analyses.Conclusion: The SIC score was an independent risk factor for NOAF in septic patients, and NOAF was an independent risk factor for predicting mortality.Keywords: sepsis, sepsis-induced coagulopathy, new-onset atrial fibrillation, association, mortality

Yang Liu,1 Lanxi Zhang,2 Jie Zhao,1,3 Ruilong Lu,1 Xuejie Shao,1 Kexin Xu,1 Jiansheng Li,1,3,4,&ast; Yange Tian1,3,&ast; 1Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province and Education Ministry of People’s Republic of China, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2School of Basic Medicine (Zhongjing School), Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 3Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 4First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiansheng Li; Yange Tian, Email li_js8@163.com; yange0910@126.comPurpose: The main objective of this study was to explore the mechanism of effective component compatibility of Bufei Yishen formula III (ECC-BYF III) in inhibiting mitochondrial oxidative stress in a rat model of chronic obstructive pulmonary disease (COPD).Methods: A549 cells exposed to cigarette smoke extract (CSE) were used to establish a model of mitochondrial oxidative damage. The cells were treated with the plasmid encoding Pkm2 and the enzymes and proteins involved in oxidative stress and mitochondrial function were measured. A rat model of COPD was established using CS and bacteria. Two different treatments were established, ECC-BYF III (5.5 mg/kg/d) and N-acetylcysteine (54 mg/kg/day). Animals were tested for pulmonary function (Vt, PEF, FVC, FEV0.1s and Cdyn) after eight weeks of therapy and were sacrificed. Pulmonary H&E staining was performed, and the total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) content were measured. The mitochondrial function was also examined. Furthermore, the Pkm2/Nrf2 signaling pathway was evaluated.Results: Overexpression of Pkm2 dramatically ameliorated the CS-induced mitochondrial oxidative damage. Further studies indicated that ECC-BYF III significantly improved mitochondrial function and inhibited oxidative stress in the lung tissues of COPD rats. Moreover, it can upregulate mitochondrial respiratory chain enzyme activity. ECC-BYF III also decreased the MDA content and increased T-SOD, GSH-Px, and T-AOC expression to facilitate oxidative homeostasis. Finally, our results indicated that the Pkm2/Nrf2 pathway is regulated by ECC-BYF III in A549 cells and lung tissue.Conclusion: These results indicate that ECC-BYF III exerts a strong effective therapeutic effect against cigarette smoke combined with bacteria-induced COPD in rats by activating the Pkm2/Nrf2 signaling pathway and restoring mitochondrial oxidative stress. Although more in vivo animal model research is needed to confirm these findings, this study contributes new data to support the conventional usage of ECC-BYF III.Keywords: chronic obstructive pulmonary disease, oxidative stress, ECC-BYF III, Pkm2, Nrf2

Jian Li,1,&ast; Li Liu,2,&ast; Zhiyun Gao,1 Xia Chuai,3 Xiaokun Liu,4 Xiaobo Zhang,2 Xinyu Zhang,2 Xiaoqing Su,2 Qian Xu,2 Zhuojun Deng2 1Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Emergency, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega Science, Chinese Academy of Sciences, Wuhan, Hubei, People’s Republic of China; 4Department of Ophthalmology, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuojun Deng, Department of Emergency, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email dengzhuojun@126.com; 37700469@hebmu.edu.cnPurpose: The incidence of visceral leishmaniasis (VL), a global infectious disease, has been on the rise in China’s Hebei province. When patients achieve clinical cure, they often do not reach an etiological cure, which may lead to recurrence of the disease. Here, we report a case of visceral leishmaniasis with a negative blood smear and bone marrow cytology.Patients and Methods: A 65-year-old man and bronchoalveolar lavage fluid mNGS.Results: A 65-year-old man developed a chronic fever, anorexia, splenomegaly, and pancytopenia. The blood metagenomic second-generation sequencing (mNGS) revealed Leishmania sequence readings, which led to the diagnosis of VL. After sodium antimony gluconate treatment, the blood smear and bone marrow cytology revealed no Leishmania bodies. However, pancytopenia and respiratory failure did not fully subside, and cardiotoxic damage emerged. The bronchoalveolar lavage fluid (BALF) mNGS was performed to detect the pathogen. Through BALF mNGS, Leishmania sequence was still detectable. Therefore, after the ECG returned to normal, antimony sodium gluconate was administered as a next course of treatment.Conclusion: BALF mNGS may assist in evaluating the therapeutic efficacy of VL with respiratory failure, especially in patients with negative blood and bone marrow cytology.Plain Language Summary: Accurate detection of visceral leishmaniasis is essential for clinical diagnosis.It is uncommon to use alveolar lavage fluid mNGS in etiological diagnosis.Patient with negative bone marrow cytology may refer to alveolar lavage fluid mNGS. Keywords: visceral leishmaniasis, metagenomic second-generation sequencing, bronchoalveolar lavage fluid, parasite diseases, case report

Junyi Li,1,2,&ast; Zugui Wu,3,&ast; Bin Lu,2,&ast; Congcong Li,1 Shuai Wang,1 Jiahao Zhang,1 Xingxing Shen,1 Ruian Xiang,1 Jiahao Chen,1 Tao Jiang,1 Chuanxi Zhao,1 Wengang Liu,1 Xuemeng Xu1 1Department of Orthopedics and Traumatology, The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Osteoarthropathy II, Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Luoyang, People’s Republic of China; 3Department of Orthopedics and Traumatology, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming Municipal Hospital of Traditional Chinese Medicine, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuemeng Xu; Wengang Liu, Department of Orthopedics and Traumatology, The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, No. 60 Hengfu Road, Guangzhou, 510030, People’s Republic of China, Email xuxuemeng@163.com; 914194079@qq.comPurpose: Our study aims to evaluate differences in muscle parameters of the quadriceps muscles in patients with knee osteoarthritis (KOA) in older adults.Methods: The study included 40 patients diagnosed with unilateral knee osteoarthritis in the KOA group (KG) and 40 asymptomatic elderly individuals in the control group (CG). Muscle ultrasonic mean echo intensity and shear modulus, as well as tone and stiffness of the rectus femoris (RF), vastus medialis (VM), and vastus lateralis (VL) were analyzed. Additionally, clinical correlations were performed.Results: In the KG group, there were significant differences in echo intensity, shear modulus, and tone between the affected and unaffected sides for RF (p=0.003, 0.019, 0.014), while VM showed significant differences in shear modulus and tone (p=0.006, 0.002). Additionally, VL exhibited significant differences in echo intensity, shear modulus, and stiffness (p=0.007, 0.006, 0.010). Compared to the CG group, the KG group showed significant differences in echo intensity of the affected side RF (p=0.001). VM exhibited statistically significant differences in echo intensity and shear modulus (p < 0.001, p=0.008), while VL showed statistically significant differences in echo intensity, tone, and stiffness (p < 0.001, p=0.028, p < 0.001). The correlation results showed that patients with unilateral KOA, VM, and VL echo intensity were correlated with K-L grade (r = 0.443, p=0.004; r = 0.469, p=0.002). The tone of VL was correlated with VAS and WOMAC (r = 0.327, p=0.039; r = 0.344, p=0.030).Conclusion: The parameters of the quadriceps femoris muscle exhibit asymmetry between the affected and unaffected sides in patients with unilateral KOA, as well as a difference between the dominant side of healthy older individuals and the affected side of KOA.Keywords: knee osteoarthritis, quadriceps femoris, ultrasound, muscle tone, stiffness

Xuebing Zhang,1 Lianjie Wang,1 Ge Wang,1 Jiayue Li,1 Yiming Mu,2 Shidong Wang,1 Xiaoran Li1 1Department of Endocrinology, Dongzhimen Hospital Beijing University of Chinese Medicine, Beijing 100700, People’s Republic of China; 2Department of Endocrinology, First Medical Centre of Chinese PLA General Hospital, Beijing 100853, People’s Republic of ChinaCorrespondence: Shidong Wang; Xiaoran Li, Email A2082@bucm.edu.cn; 466187309@qq.comBackground: Nonalcoholic fatty liver disease (NAFLD) has become a major global health burden, which increases the risk of extra-hepatic complications such as type 2 diabetes mellitus (T2DM), dyslipidemia, metabolic syndrome (MetS), and cardiovascular disease (CVD). However, NAFLD remains underappreciated and underdiagnosed. Our study aimed to explore the prevalence of NAFLD and the association between NAFLD and CVD events among adults aged 40 and older in Northern China.Methods: This study was conducted in the Shijingshan district of Beijing, China from November 2011 to August 2012. A total of 18891 subjects were recruited in the study. The information including demographical information, lifestyle, previous history of diabetes, hypertension, dyslipidemia, CVD, and liver disease were gathered. Data on physical examination, blood lipid profile, fasting blood glucose, and 2-hour blood glucose were recorded. Determination of MetS was according to T2DM guideline of Chinese Diabetes Society (2020 edition). The association between CVD and NAFLD was evaluated by multivariate logistic regression.Results: The prevalence of NAFLD was 15.2%. After adjustment for age, smoking status, alcohol intake, WC, hypertension, dyslipidemia and hyperglycemia, the odds ratios (ORs) of CVD in men were 1.622 (95%CI: 1.345– 1.957) and 1.990 (95%CI: 1.709– 2.316) in women with NAFLD, compared with the subjects without NAFLD.Conclusions: NAFLD is independently associated with increased risk of CVD development.Keywords: nonalcoholic fatty liver disease, metabolic syndrome, cardiovascular disease, middle-aged and elderly, Chinese

Xiujing Lu,&ast; Xi Lan,&ast; Xiaoqian Fu, Jing Li, Min Wu, Lu Xiao, Yachang Zeng Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yachang Zeng, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People’s Republic of China, Email zengyachang@163.comPurpose: Preeclampsia (PE) is a serious complication of obstetrics and represents a significant challenge in terms of understanding its underlying mechanism. It has been shown that a number of disorders involve dysregulation of the CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl-terminal domain 2 (CITED2). However, the relationship between PE and CITED2 is still mostly unclear. This work aimed to confirm the hub genes linked to PE and explore the roles of CITED2 in trophoblast using experimental and bioinformatic methods.Methods: To determine the hub genes, bioinformatics research was performed on two datasets from the Gene Expression Omnibus (GEO) public database. Immune infiltration analysis and enrichment analysis were also used to identify the related pathways and immune cells. PCR and WB were then used to validate the mRNA and protein levels of CITED2 in the PE samples. Finally, the expression of CITED2 was knocked down using siRNA to investigate the function of CITED2 in trophoblast development in vitro.Results: The study’s findings showed that the NOTCH signaling pathways, glycolysis, and hypoxia were the main areas of enrichment for the six PE-related genes that were tested. The results of immune infiltration suggest that activated NK cells and regulatory T cells may play an important role in this process. CITED2 was significantly upregulated in the PE placenta. In functional tests, the knockdown of CITED2 may enhance apoptosis while suppressing migration, invasion, and proliferation of cells.Conclusion: This study offers important proof that CITED2 influences trophoblast cell function and may one day be a therapeutic target for PE.Keywords: preeclampsia, CITED2, placenta, cell function, bioinformatics

Mi Zhou,1 Jieyun Li,1 Xinang Xiao,1 Jiekee Lim,1 Zhaoxia Xu1,2 1School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Health Identification and Assessment, Shanghai, People’s Republic of ChinaCorrespondence: Zhaoxia Xu, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New Area, Shanghai, 201203, People’s Republic of China, Email zhaoxia7001@shutcm.edu.cnPurpose: To analyse the current status of outcome indicators in randomised controlled trials (RCTs) of traditional Chinese medicine (TCM) for the treatment of coronary heart disease (CHD) with deficiency of qi and yin, and to provide a basis for constructing a core indicator set (COS) for TCM treatment of CHD.Methods: We searched the database of China National Knowledge Infrastructure (CNKI), PubMed,etc. 8 databases in the last 5 years. RCTs of TCM for CHD included in core journals were evaluated for the risk of bias of the included studies, and the current status of the selection of outcome indicators was statistically analysed.Results: A total of 39 RCTs with a sample size of 44~398 cases were included, and 164 outcome indicators were reported, with a frequency of 383 applications. The outcome indicators were categorised into 6 indicator domains according to their functional attributes, which were, in descending order, safety indicators, physicochemical examination, effective rate, economic assessment, disease evidence score, and quality of life. The top 3 indicators in terms of frequency of application of outcome indicators were safety indicators, physical and chemical examination indicators, and efficiency, among which electrocardiogram, inflammation indicators, and clinical efficacy were the most frequently used; there were many different types of measurement tools for outcome indicators, among which total efficiency and TCM symptom points were the most frequently used; the time point of measurement was not the same.Conclusion: The RCTs of TCM for CHD in the last 5 years have many shortage in the selection of outcome indicators, and should actively promote the construction of the COS of TCM for CHD.Keywords: Coronary heart disease, deficiency of qi and yin, TCM, randomised controlled trials, outcome indicators, core indicator set

Xianjun Xiao,1,&ast; Peiwen Xue,1,&ast; Xiangyun Yan,2,&ast; Yanqiu Li,2,&ast; Yunzhou Shi,2 Haiyan Qin,2 Di Qin,2 Wei Cao,2 Zihao Zou,2 Lu Wang,2 Rongjiang Jin,1 Ying Li,2 Junpeng Yao,2 Juan Li1,3 1School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, People’s Republic of China; 2Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, People’s Republic of China; 3Affiliated Sichuan Provincial Rehabilitation Hospital of Chengdu University of TCM, Chengdu, Sichuan, 611135, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junpeng Yao; Juan Li, Email yjp@cdutcm.edu.cn; 785939016@qq.comBackground: Emerging evidence links gut microbiota and their by-products, notably short-chain fatty acids (SCFAs), to urticaria. This study employs multiple Mendelian Randomization (MR) analyses to unravel the complex interactions among gut microbiota, SCFAs, and different subtypes of urticaria, aiming to elucidate the underlying mechanisms and enhance future clinical research.Methods: We analyzed published genome-wide association study (GWAS) summary statistics to identify associations between gut microbiota and three common subtypes of urticaria: spontaneous, dermatographic, and temperature-triggered. Initial two-sample and reverse MR analyses explored the causality in these relationships. Subsequent multivariate MR analyses investigated the role of SCFAs in modulating these interactions, with multiple sensitivity analyses to ensure robustness.Findings: Specific taxa were differently associated with various urticaria subtypes. From microbiota to urticaria: one taxon was negatively associated with dermatographic urticaria; seven taxa were negatively associated and four positively associated with temperature-triggered urticaria; four taxa were negatively associated and six positively associated with spontaneous urticaria. Conversely, from urticaria to microbiota: five taxa were negatively associated with dermatographic urticaria; four were negatively and two positively associated with temperature-triggered urticaria; and two were negatively associated with spontaneous urticaria. These associations were observed at a nominal significance level (P < 0.05). After applying Bonferroni correction for multiple testing, these associations did not reach statistical significance. The observed trends, however, provide insights into potential microbiota-urticaria interactions. Multivariate MR analyses elucidated the role of SCFAs, particularly acetate, which plays a crucial role in modulating immune response. Adjusting for acetate revealed direct effects of Actinobacteria, Bifidobacteriales, and Bifidobacteriaceae on spontaneous urticaria, with corresponding mediation effects of − 22%, − 24.9%, and − 24.9% respectively. Similarly, adjustments for Alcaligenaceae and Betaproteobacteria indicated significant negative effects of acetate on dermatographic and spontaneous urticaria, with mediation effects of − 21.7% and − 23.7%, respectively.Conclusion: This study confirms the interconnected roles of gut microbiota, SCFAs, and urticaria. It highlights SCFAs’ potential mediating role in influencing urticaria through microbiota, providing insights for future therapeutic strategies.Keywords: urticaria, short-chain fatty acids, gut microbiota, gut-skin axis, Mendelian randomization

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

Hui Ao, Huizhu Song, Jing Li Department of Pharmacy, the Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of ChinaCorrespondence: Jing Li, Department of Pharmacy, the Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, No. 299, Qingyang Road, Wuxi, Liangxi District, People’s Republic of China, Email lijingwuxi@sina.comPurpose: The increasing multi-drug resistance (MDR) is a serious threat to human health. The appropriate use of antibiotics can control the progression of MDR and clinical pharmacists play an important role in the rational use of antibiotics. There are many factors that influence the effectiveness of multi-drug resistant organisms (MDRO) infection consultations. The study aimed to establish a model to predict the outcome of consultation and explore ways to improve clinical pharmacy services.Patients and methods: Patients diagnosed with MDRO infection and consulted by clinical pharmacists were included. Univariate analysis and multivariate logistic regression analysis were used to identify independent risk factors for MDRO infection consultation effectiveness, and then a nomogram was constructed and validated.Results: 198 patients were finally included. The number of underlying diseases (OR=1.720, 95% CI: 1.260– 2.348), whether surgery was performed prior to infection (OR=8.853, 95% CI: 2.668– 29.373), ALB level (OR=0.885, 95% CI: 0.805~0.974), pharmacist title (OR=3.463, 95% CI: 1.277~9.396) and whether the recommendation was taken up (OR=0.117, 95% CI: 0.030~0.462) were identified as independent influences on the effectiveness of the consultation. The nomogram prediction model was successfully constructed and the AUC of the training set and the verification set were 0.849 (95% CI: 0.780– 0.917) and 0.761 (95% CI: 0.616– 0.907) respectively. The calibration curves exhibited good overlap between the data predicted by the model and the actual data.Conclusion: A nomogram model was developed to predict the risk of consultation failure and was shown to be good accuracy and good prediction efficiency, which can provide proactive interventions to improve outcomes for potentially treatment ineffective patients.Keywords: multi-drug resistance, nomogram, clinical pharmacist, consultation, clinical pharmacy services

Zhuying Zhang,1,2,&ast; Mai Shi,1,2,&ast; Jinghui Li,3 Dian Chen,1,2 Jie Ren,1,2 Zhenghui Li,1,2 Hsiaohan Tuan,1,2,&ast; Yi Zhao1,2,&ast; 1Department of Dermatology, Beijing Tsinghua Changgung Hospital, Beijing, People’s Republic of China; 2Photomedicine Laboratory, Institute of Precision Medicine, Tsinghua University, Beijing, People’s Republic of China; 3School of Medicine, Tsinghua University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Zhao; Hsiaohan Tuan, Department of Dermatology, Beijing Tsinghua Changgung Hospital, No. 168 Litang Road, Changping District, Beijing, 102218, People’s Republic of China, Tel +86-13718646181 ; +86-18610015166, Email zhaoyimd@tsinghua.edu.cn; dxha00337@btch.edu.cnIntroduction: The aging of the skin, which is affected by both external and internal causes, can reflect the external age and the internal health status. While the aging characteristics differ across ethnic groups, the specific changes in skin aging within the Chinese population have been underexplored. Moreover, investigating the similarity of aging skin characteristics between parent-offspring pairs remains uncharted territory. This study aims to fill these gaps by examining the skin aging features of Chinese women and assessing the similarity in aging skin characteristics between mother-daughter pairs.Methods: A total of 40 mother-daughter pairs were recruited and analyzed. The perceived ages of the participants were evaluated, and their aging skin traits were systematically graded. Statistical methods were employed to discern the trends of the aging skin characteristics. By introducing a novel similarity parameter, we compared whether various skin aging characteristics have similar patterns between mothers and daughters.Results: Our findings indicate that age 50 represents a pivotal point in skin aging. Beyond this age, the increase in rhytides and laxity scores accelerated noticeably, whereas the escalation in dyschromia scores became less marked. By introducing similar parameters between mother-daughter pairs and the radar map, we discovered that the skin aging characteristics are remarkably consistent between mother-daughter pairs.Conclusion: Understanding the main aging skin characteristics of different age groups can allow caregivers to devise treatments for preventing skin aging in women of various ages. The mother’s skin aging trend is also significant for the daughter’s skin aging prevention.Plain Language Summary: Skin aging, a complex process influenced by both internal and external factors, exhibits distinct patterns across ethnic groups. Despite this, the specific aging characteristics within the Chinese population and the hereditary similarities between parents and offspring have not been thoroughly investigated. To address this gap, our study focused on the skin aging features of Chinese women and explored the resemblance in these features between mother-daughter pairs. Eighty-seven women from the same community, including 40 mother-daughter pairs, participated in our study. We assessed how old each participant appeared to be and methodically evaluated their skin aging signs by a modified scale. With the introduction of a new similarity parameter, we further examined the extent to which skin aging traits showed parallel trends between mothers and their daughters.Our findings pinpoint age 50 as a pivotal moment in the skin aging trajectory, where the increase in wrinkles and skin laxity becomes more pronounced, contrasting with a deceleration in skin discoloration. Remarkably, a consistent pattern of aging characteristics was observed between mother-daughter pairs, suggesting a potential genetic influence. This study not only sheds light on the specific skin aging patterns among Chinese women but also underscores the significance of genetic factors in shaping these patterns. The insights gained pave the way for developing targeted interventions for skin aging prevention and treatment, emphasizing the importance of considering familial aging trends.Keywords: Chinese female, skin aging pattern, aging characteristics, intergenerational analysis

Ying Zhu,1 Tao Zeng,1 Hongbo Huai,2 Tong Zhu,3 Ying Huang,3 Jing Li,3 Jian Lin3 1Department of Pain Medicine, Kunshan Integrated TCM and Western Medicine Hospital, Kunshan, 215332, People’s Republic of China; 2Rehabilitation Department, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China; 3Department of Pain Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of ChinaCorrespondence: Hongbo Huai; Tong Zhu, Email Huaihongbo@njglyy.com; 1911033561@qq.comPurpose: This retrospective study was to investigate the efficacy of Gasserian ganglion pulsed radiofrequency therapy (PRF) combined with low-dose morphine injection in the treatment of refractory ophthalmic herpetic neuralgia.Patients and methods: A total of 40 intractable ophthalmic herpetic neuralgia patients who received Gasserian ganglion PRF therapy in Pain Department of Nanjing Drum Tower Hospital were retrospectively analysed, with an average age of 70.2 ± 8.5 years and an average disease course of 30 (30, 60) days. According to different interventions, they were divided into two groups: Group A, 19 patients who received Gasserian ganglion PRF therapy combined with 0.2 mg morphine injection via puncture needle; Group B, 21 patients who received only Gasserian ganglion PRF therapy. Data related to the length of hospital stay and associated costs, numerical rating scale scores (NRS), intravenous morphine and oral oxycodone doses during hospitalization, Short form McGill pain questionnaire and Pittsburgh sleep quality index (PSI), and conditions of opioid use and postherpetic neuralgia after discharge were collected in the two groups. SPSS 25.0 was used to perform statistical analysis on data.Results: The hospital stay, hospitalization costs, and oxycodone dosages for Group A were lower than those for Group B (p = 0.02, p = 0.015 and p = 0.023, respectively). The proportion of patients in group A still taking oral opioids 1 month after discharge and experiencing postherpetic neuralgia 6 months after the onset was lower than that in group B (p = 0.004 and p = 0.049). The NRS upon discharge, as well as the McGill and PSQI scores at the time of discharge and at 1, 3, 6 and 12 months post-discharge, were all significantly reduced compared to those measured upon admission in two groups (p = 0.000).Conclusion: Gasserian ganglion PRF therapy combined with low-dose morphine injection offers an alternative option for managing intractable herpetic neuralgia and prevention of postherpetic neuralgia in ocular branches.Clinical Trial Registration: ChiCTR2300073281.Keywords: ophthalmic, herpetic neuralgia, pulsed radiofrequency, Gasserian ganglion, opioids

Yu-Qing Tan,1,&ast; Wang Zhang,2,&ast; Zi-Cong Xie,1 Jun Li,1 Heng-Wen Chen3 1Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 2Department of Pharmacy, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 3New Drug Research and Development Office, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Li; Heng-Wen Chen, Email 13051458913@163.com; chenhengwen@163.comAbstract: Cardiovascular diseases (CVDs) tend to affect the young population and are associated with a significant economic burden and psychological distress to the society and families. The physiological and pathological processes underlying CVDs are complex. Ca2+/calmodulin-dependent kinase II (CaMK II), a protein kinase, has multiple biological functions. It participates in multiple pathological processes and plays a central role in the development of CVDs. Based on this, this paper analyzes the structural characteristics and distribution of CaMK II, the mechanism of action of CaMK II, and the relationship between CaMK II and CVDs, including ion channels, ischemia-reperfusion injury, arrhythmias, myocardial hypertrophy, cardiotoxicity, hypertension, and dilated cardiomyopathy. Given the different regulatory mechanisms of different isoforms of CaMK II, the clinical use of specific targeted inhibitors or novel compounds should be evaluated in future research to provide new directions.Keywords: CaMK II, cardiovascular diseases, ischemia-reperfusion injury, arrhythmias, myocardial hypertrophy

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

Zhanjie Li,1,&ast; Jian Li,2,&ast; Chuanlong Zhu,3 Shengyuan Jiao1,2 1Department of Infection Control, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Department of Disease Prevention and Control, Air Force Hospital of Eastern Theater, Nanjing, People’s Republic of China; 3Department of Infections Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengyuan Jiao, Department of Infection Control, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China, Tel +8618021136781, Email 17319884906@163.com Chuanlong Zhu, Department of Infections Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210009, People’s Republic of China, Tel +8617714316539, Email zhuchuanlong@jsph.org.cnBackground: To identify risk factors for acquiring HAIs in COVID-19 patients and establish visual prediction model.Methods: Data was extracted from Xinglin Hospital Infection Monitoring System to analyze COVID-19 patients diagnosed between December 1, 2022, and March 1, 2023. Univariate and multivariate analyses were conducted to identify risk factors. Predictive signature was developed by selected variables from lasso, logistic regression, and their intersection and union. Models were compared using DeLong’s t-tests. Likelihood ratio (LR) and Youden’s index was used to evaluate the predictive performance. Nomogram was constructed using optimal variables ensemble, prediction accuracy was evaluated using AUC, DCA and calibration curve.Results: Total of 739 patients met the criteria, of which 53 (7.2%) were HAIs. NSAIDs, surgery, fungi and MDRO detected, hormone drugs and LYMR were independent risk factors. Lasso model screened seven variables, and logistic model identified six risk factors. Union model performed the best with the maximum of the Youden’s index is 0.703, the sensitivity is 95.6%, the specificity is 74.7%, the LR is 3.778. The best AUC of union model is 0.953 (0.928– 0.978), and the accuracy is 87.5%. DCA indicated that the union model provided the best net benefits and calibration curve demonstrated good predictive agreement.Conclusions: HAIs prediction in COVID-19 patients is feasible and beneficial to improve prognosis. Physicians can use this nomogram to identify high-risk COVID-19 populations for HAIs and tailor follow-up strategies.Keywords: risk factors, healthcare-associated infection, COVID-19, nomogram, prediction model

Xinling Zhao,1,2,&ast; Huijin Jie,3,&ast; Jun Wang,1 Yu Liu,4 Yilin Liu,2 Fuyi Qin,2 Qing Long,2 Xi Hou,5 Xin-Wen Zhang,6 Wenzhi Wu,7 Xiaoqin Wu,2 Jing Li,8 Yong Zeng2 1Department of Clinical Psychology, People’s Hospital of Chongqing Liang Jiang New Area, Chongqing, People’s Republic of China; 2Department of Psychiatry, the Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 3Haining Fourth People’s Hospital, Haining, People’s Republic of China; 4Department of Psychiatry, the First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 5Department of Clinical Psychology, The Sixth Affiliated Hospital of Kunming Medical University, Yuxi, People’s Republic of China; 6Department of Psychiatry, Hong He Second People’s Hospital, Jian Shui, People’s Republic of China; 7Faculty of psychology, Beijing Normal University, Beijing, People’s Republic of China; 8Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Li; Yong Zeng, Email lijingjingjing222@163.com; zengyong@kmmu.edu.cnBackground: Adolescents with major depressive (MDD) episodes associated with childhood trauma have a poorer response to treatment and a higher risk of suicide. The underlying etiology is unclear. Brain-derived neurotrophic factor (BDNF) could improve depressive symptoms by down-regulating mammalian target of rapamycin (mTOR) signaling pathways, which was involved in adverse environmental stimuli during neurodevelopment. BDNF and mTOR have not been reported simultaneously in adolescents with major depressive episodes associated with childhood trauma.Methods: Childhood Trauma Questionnaire-Short Form (CTQ-SF), Children’s Depression Inventory (CDI) and Children’s Depression Rating Scale-Revised (CDRS-R) were used to evaluate the recruited adolescents with major depression episodes. Serum BDNF and p-mTOR levels were measured by ELISA in 31 adolescents with major depression episodes with childhood trauma and 18 matched healthy control.Results: The serum levels of BDNF were significantly lower (p< 0.001); and the serum levels of p-mTOR were high (p=0.003) in the adolescents with the first episode of major depressive episode accompanied by childhood trauma. Of the 31 adolescents with major depressive episodes, 17 had suicide or self-injury. Compared with the healthy control group, the serum levels of BDNF in patients with suicide or self-injury were lower than those without suicide or self-injury(p< 0.001); the serum levels of p-mTOR were higher than those without suicide or self-injury (p=0.01). While in patients without suicide or self-injury, only serum p-mTOR was significantly higher than that in healthy group (p=0.028). BDNF was negatively correlated with CDRS-R (r=− 0.427, p=0.006), p-mTOR was positively correlated with CDI (r=0.364, p=0.048). According to Receiver Operating Characteristic Curve (ROC), the combination of serum BDNF and p-mTOR levels have better diagnostic value.Conclusion: Neurotrophic and signaling pathways, involving BDNF and p-mTOR, may play a role in adolescent MDD with a history of childhood trauma, especially patients with suicide and self-injury tendencies.Keywords: brain-derived neurotrophic factor, p-mTOR, major depressive disorder, suicide, adolescent, childhood trauma

Xin Qiu,1,2,&ast; Shuang Shen,1,&ast; Donghong Lu,2 Nizhen Jiang,3 Yifei Feng,3 Jindu Li,1 Chenglei Yang,1 Bangde Xiang1,4,5 1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 3Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 4Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning, People’s Republic of China; 5Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bangde Xiang; Chenglei Yang, Email xiangbangde@gxmu.edu.cn; chenglei2017yang@163.comBackground: Hepatocellular carcinoma (HCC) presents a significant global health challenge due to its poor prognosis and high recurrence rates post-surgery. This study examines the predictive efficacy of the Advanced Lung Cancer Inflammation Index (ALI) in assessing the post-hepatectomy prognosis of patients with HCC.Methods: A cohort comprising 1654 HCC patients who underwent hepatectomy at Guangxi Medical University Cancer Hospital from 2013 to 2019 was enrolled. Patients were stratified into two groups according to the median ALI level, and then subjected to propensity score matching (PSM) in a 1:1 ratio. Kaplan-Meier survival curves, the traditional Cox proportional hazards (CPH) model, and machine learning (ML) models were employed to analyze and evaluate ALI’s prognostic significance. Furthermore, ALI’s prognostic value in digestive system tumors was validated via analysis of the National Health and Nutrition Examination Survey (NHANES) database.Results: After applying PSM, a final cohort of 1284 patients, categorized into high and low ALI groups, revealed a significantly reduced survival time in the low ALI cohort. Univariate and multivariate Cox analyses identified ALI, BCLC stage, CK19, Hepatitis B virus (HBV) DNA, lymph node metastasis, and microvascular invasion (MVI) as independent predictors of prognosis. Both traditional CPH and ML models incorporating ALI demonstrated excellent predictive accuracy, validated through calibration curves, time-dependent ROC curves, and decision curve analysis. Furthermore, the prognostic value of ALI in digestive tumors was confirmed in the NHANES database.Conclusion: The ALI exhibits potential as a prognostic predictor in patients with HCC following hepatectomy, providing valuable insights into postoperative survival.Keywords: advanced lung cancer inflammatory index, ALI, hepatocellular carcinoma, HCC, prognosis, Cox regression, machine learning, ML

Jinxi Li,1,&ast; Yiduo Lu,2,&ast; Xuyun Zhang,1 Gang Liu3 1International Medical College, Chongqing Medical University, Chongqing, People’s Republic of China; 2College of Basic Medical Sciences, Naval Medical University, Shanghai, People’s Republic of China; 3Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gang Liu, Email 203745@hospital.cqmu.edu.cnIntroduction: The burden of cardiometabolic diseases (CMDs), defined as stroke, coronary artery disease, and diabetes mellitus, continues to pose a global challenge. Sleep duration has been linked to cardiovascular health. However, there is a lack of focused investigations on CMDs in underdeveloped areas of China.Purpose: This study aimed to examine the relationship between sleep duration and CMDs among residents from southwest China.Patients and Methods: This large cross-sectional study screened data from the National Key Research and Development Program (2018YFC1311400). Based on sleep duration reported through a standardized questionnaire, encompassing the sleep patterns of the past five years, participants were classified into three groups: < 6, 6– 8, > 8 hours. Baseline characteristics were compared, and Poisson regression models were used to assess the relationship between sleep duration and CMDs. Subgroup analysis was conducted based on age and gender.Results: This study included 28,908 participants with an average age of 65.6 ± 10.0 years, of whom 57.6% were female. The overall prevalence of CMDs was 22.6%. After multivariate adjustments, the prevalence ratios (PR) (95% CI) for CMDs across the three groups (6– 8h, < 6h and > 8h) were: reference, 1.140 (1.068– 1.218), 1.060 (0.961– 1.169) (P for trend =0.003), respectively. The subgroup analysis revealed that among older females, a longer sleep duration (> 8h) was also associated with an increased prevalence risk of CMDs, with PR 1.169 (1.001– 1.365) (p=0.049).Conclusion: A shorter sleep duration (< 6 hours) was associated with an increased risk of CMDs in the general population, while a longer sleep duration (> 8 hours) also raised the prevalence risk among older females.Keywords: cardiometabolic disease, sleep duration, Southwest China

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

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

Daniyal H Mirza,1,&ast; Lucy Zha,1,&ast; Claudia See,2 Isabella N Paoletti,1 Feng Dai,3 Mark Hocevar,4 Jinlei Li,5 Daniel Wiznia6 1Yale College, New Haven, CT, 06520-8241, USA; 2Yale School of Medicine, New Haven, CT, 06520, USA; 3Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, CT, 06520, USA; 4Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA; 5Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, 06510, USA; 6Department of Orthopedics and Rehabilitation, Yale School of Medicine, New Haven, CT, USA; Department of Mechanical Engineering & Materials Science, School of Engineering & Applied Science, Yale University, New Haven, CT, USA&ast;These authors contributed equally to this workCorrespondence: Jinlei Li, Department of Anesthesiology, Yale University School of Medicine, 20 York Street, New Haven, CT, 06510, USA, Tel +1 917-601-6828, Email jinlei.li@yale.eduBackground: The most common route of opioid delivery is nurse-administered pills. However, there are numerous challenges such as nursing burden, opioid diversion, medication delay, and patient dissatisfaction. In this study, we conducted two surveys, first to assess patients’ and nurses’ opinions on the current administration of opioids in pill form, followed by their attitudes towards an innovative concept of oral medication delivery based on a medical device currently undergoing research and development within the University, patient-controlled dispenser and deactivator (PCDD) that allows patients to self-administer liquid oral opioids on demand based on physician prescription.Methods: Questionnaires were developed, verified and deployed to assess nurse and post-surgical patient opinions on the current administration of opioids in pill form, as well as the proposed new concept of patient -controlled administration of oral liquid medication via an illustration of PCDD, from September 2022 through July 2023 at a major academic tertiary care center. Quantitative and qualitative data were collected from postoperative patients and nurses from surgical specialties including General Surgery, Surgical Oncology, Trauma Surgery, Orthopedics, and Neurosurgery.Results: Forty-three patients and 53 nurses were interviewed. Seventy percent of patients frequently called nurses for pain medication post-surgery 1– 4 times daily, and 32% of patients were told each day by nurses that they could not receive medication because they were not due yet. Medication delay caused 24% of patients to worry about nursing availability for medication delivery. Likewise, nurses reported that half of patients receive delayed medication (22 minutes median delay time) and half of nursing time was spent administering pain medication. Nurses expressed moderate satisfaction with their current delivery of medication (median satisfaction score 6.5 out of 10). When being introduced to the concept of PCDD via a product illustration, 15% of patients said that they prefer liquid medication and 51% said they prefer PCDD or were interested in trying it.Conclusion: Nurse-administered pills are a common but suboptimal method for postoperative pain management. Based on patient and nurse feedback, patient controlled self-administered liquid oral opioid delivery is conceptually innovative, practically viable and potentially a preferred alternative for timely and less nurse-exhaustive pain management.Keywords: pain management, opioid, survey, nursing, patient-controlled analgesia pump

Bohai Du,1 Tianlan Li,1 Haoqi He,1 Xun Xu,2 Chunmei Zhang,1 Xianzhu Lu,1 Yuhan Wang,1 Jingyi Cao,1 Yinghan Lu,1 Yiwa Liu,1 Shanshan Hu,1 Juxiao Li,1 Li Li,1 Ming Shi1 1Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, Guangdong Province, 523808, People’s Republic of China; 2Experimental Animal Center, Guangdong Medical University, Dongguan, Guangdong Province, 523808, People’s Republic of ChinaCorrespondence: Li Li; Ming Shi, School of Public Health, Guangdong Medical University, Dongguan, Guangdong Province, 523808, People’s Republic of China, Tel +86-15889530426 ; +86-769-22896568, Email lily2017@gdmu.edu.cn; shiming@gdmu.edu.cnIntroduction: Studies have shown that microplastics (MPs) and nanoplastics (NPs) could accumulate in the human body and pose a potential threat to human health. The purpose of this study is to evaluate the biodistribution and toxicity of MPs/NPs with different particle sizes comprehensively and thoroughly.Methods: The purpose of this study was to investigate the biodistribution and in vivo toxicity of polystyrene (PS) MPs/NPs with different sizes (50 nm, 100 nm, and 500 nm). The BALB/c mice were given 100 μL of PS50, PS100 and PS500 at the dosage of 1 mg/kg BW or 10 mg/kg BW, respectively, by gavage once a day. After 28 consecutive days of treatment, the biodistribution of differently sized PS MPs/NPs was determined through cryosection fluorescence microscopy and fluorescent microplate reader analysis, and the subsequent effects of differently sized PS MPs/NPs on histopathology, hematology and blood biochemistry were also evaluated.Results: The results showed that the three different sizes of PS MPs/NPs were distributed in the organs of mice, mainly in the liver, spleen, and intestine. At the same time, the smaller the particle size, the more they accumulate in the body and more easily penetrate the tissue. During the whole observation period, no abnormal behavior and weight change were observed. The results of H&E staining showed that no severe histopathological abnormalities were observed in the main organs in the low-dose exposure group, while. Exposure of three sizes of PS MPs/NPs could cause some changes in hematological parameters or biochemical parameters related to heart, liver, and kidney function; meanwhile, there were size- and dose-dependencies.Conclusion: The biological distribution and toxicity of plastic particles in mice were more obvious with the decrease of particle size and the increase of concentration of plastic particles. Compared with MPs, NPs were easier to enter the tissues and produce changes in liver, kidney, and heart functions. Therefore, more attention should be paid to the toxicity of NPs.Keywords: microplastics, nanoplastics, polystyrene, size, biodistribution, nanotoxicology

Beibei Luo,1 Baolong Pan,2 Guancheng Zhao,1 Jiefen Li,1 Li Sun1 1Clinical Laboratory, People’s Hospital of Yuxi City, the Sixth Affiliated Hospital of Kunming Medical University, Yuxi City, Yunnan Province, 653100, People’s Republic of China; 2Physical Examination Center, People’s Hospital of Yuxi City, the Sixth Affiliated Hospital of Kunming Medical University, Yuxi City, Yunnan Province, 653100, People’s Republic of ChinaCorrespondence: Baolong Pan, Physical Examination Center, People’s Hospital of Yuxi City, the Sixth Affiliated Hospital of Kunming Medical University, 21 Nieer Road, Yuxi City, Yunnan Province, 653100, People’s Republic of China, Email pbl1210@126.comIntroduction: Serum magnesium is a crucial mineral within the human body. It is imperative for diabetic patients to maintain optimal serum magnesium levels. We focus on the relationship between glycemic control and serum magnesium in type 2 diabetes mellitus (T2DM).Methods: The retrospective, observational, cross-sectional study comprised 1694 patients recruited from the People’s Hospital of Yuxi. Fasting blood samples were collected for analysis, accompanied by the recording of participants’ demographic characteristics. Patients were categorized into two groups based on whether their glycosylated hemoglobin (HbA1c) levels < 7%. A t-test was employed to identify significant differences between the two groups. Correlation coefficients were calculated using Pearson’s method. A Logistic regression analysis was conducted to assess the association between variables and glycemic control. A linear regression analysis was performed to assess the relationship between serum magnesium levels and HbA1c.Results: Patients with poor glycemic control exhibited elevated age, low-density lipoprotein (LDL-C), fasting plasma glucose (FPG), and homeostasis model assessment (HOMA-IR) compared to those with good glycemic control (P < 0.001). Additionally, total cholesterol (TC) levels were significantly higher in patients with poor glycemic control. Conversely, high-density lipoprotein (HDL-C) and serum magnesium levels were lower in patients with poor glycemic control. Serum magnesium levels exhibited negative correlations with HOMA-IR (r = − 0.05, P < 0.05), HbA1c (r = − 0.29, P < 0.05), and FPG (r = − 0.20, P < 0.05). Moreover, serum magnesium was significantly associated with reduced odds of glycemic control (OR = 0.0005, 95% CI 0.0001– 0.0027, P < 0.001).Conclusion: The serum magnesium level in patients with T2DM is closely associated with glycemic control.Keywords: serum magnesium, glycaemic control, diabetes

Yanhong Liu,1 Qi Wang,1 Chuanlei Zheng,1,2 Zhengchun Huang,3 Jian Li,3 Ming Hao,1 Minghua Dong,1,2 Xiaoting Luo,2,4 Qingfeng Wu1,2 1School of Public Health & Healthcare Management, Gannan Medical University, Ganzhou, People’s Republic of China; 2Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, People’s Republic of China; 3School of Basic Medicine Sciences, Gannan Medical University, Ganzhou, People’s Republic of China; 4School of General Practice Medicine, Gannan Medical University, Ganzhou, People’s Republic of ChinaCorrespondence: Qingfeng Wu, Gannan Medical University, Rongjiang New District College Park, Ganzhou, Jiangxi, 341000, People’s Republic of China, Tel +86-797-8169713, Fax +86-797-8169600, Email wuqf2006@gmu.edu.cnPurpose: The prevalence of diabetes in China is increasing, influenced by economic and genetic factors, with varying rates across regions. The Hakka population in Ganzhou city has unique exposures compared to surrounding districts, while limited research reported the epidemiological characteristics of type 2 diabetes mellitus (T2DM) in this population. This study aims to investigate the prevalence and influencing factors of T2DM among the population, thereby establishing a robust foundation for disease prevention and control measures.Patients and Methods: In 2017, a multistage random sampling method selected 3028 individuals from Ganzhou City’s permanent resident population. Physical examinations, blood tests, and questionnaire surveys were conducted for data collection, with binary logistic regression analysis used to examine factors affecting T2DM prevalence.Results: A total of 2978 valid samples were included in this study. The average age of the surveyed population was 52.83± 7.88 years, comprising 966 males and 2012 females. The prevalence rates of T2DM were 11.8% and 12.9% in males and females, respectively, while the standardized prevalence rate was recorded as 9.1%. Logistic regression analysis revealed that age (Odds Ratio[OR]=1.05, 95% Confidence Interval [CI]:1.03– 1.06), hypertension (OR=2.22, 95% CI:1.71– 2.93), family history of diabetes (OR= 3.54, 95% CI: 2.58– 4.85), overweight (OR=1.73, 95% CI: 1.20– 2.48), high total cholesterol (OR=1.17, 95% CI:1.09– 1.27), elevated low-density lipoprotein cholesterol (OR=1.19, 95% CI:1.00– 1.40) and serum insulin (OR=1.05, 95% CI:1.03– 1.06) were identified as significant risk factors for T2DM, Conversely, a higher level of high-density lipoprotein cholesterol (OR=0.55, 95% CI:0.36– 0.84) was found to be inversely related to T2DM development.Conclusion: The prevalence of T2DM in Ganzhou city has significantly increased. The effective implementation of comprehensive management strategies aimed at addressing hypertension, overweight, dyslipidemia, and abnormal serum insulin level is essential for promoting overall well-being and efficiently controlling the prevalence of T2DM.Keywords: type 2 diabetes mellitus, cross-sectional studies, epidemiology, influence factors

Juan Li,1,&ast; Ting Zhou,1,&ast; Pei Wang,1,&ast; Ruian Yin,1 Shengqi Zhang,1 Yile Cao,1 Lijuan Zong,1 Ming Xiao,2 Yongjie Zhang,3 Wentao Liu,4 Lingxiao Deng,5 Fei Huang,6 Jianfei Sun,7,&ast; Hongxing Wang1,&ast; 1Department of Rehabilitation Medicine, Zhongda Hospital Southeast University, Nanjing, 210024, People’s Republic of China; 2Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 3Department of Human Anatomy, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 4Department of Pharmacology, Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, Nanjing, 211166, People’s Republic of China; 5Department of Neurological Surgery, Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indianapolis, IN, 46202-2266, USA; 6Institute of Neurobiology, Binzhou Medical University, Yantai, 264003, People’s Republic of China; 7State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianfei Sun, State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, People’s Republic of China, Email sunzaghi@seu.edu.cn Hongxing Wang, Department of Rehabilitation Medicine, Southeast University Zhongda Hospital, Nanjing, 210024, People’s Republic of China, Email 101012648@seu.edu.cnBackground: Gigantocellular reticular nucleus (GRNs) executes a vital role in locomotor recovery after spinal cord injury. However, due to its unique anatomical location deep within the brainstem, intervening in GRNs for spinal cord injury research is challenging. To address this problem, this study adopted an extracorporeal magnetic stimulation system to observe the effects of selective magnetic stimulation of GRNs with iron oxide nanoparticles combined treadmill training on locomotor recovery after spinal cord injury, and explored the possible mechanisms.Methods: Superparamagnetic iron oxide (SPIO) nanoparticles were stereotactically injected into bilateral GRNs of mice with moderate T10 spinal cord contusion. Eight-week selective magnetic stimulation produced by extracorporeal magnetic stimulation system (MSS) combined with treadmill training was adopted for the animals from one week after surgery. Locomotor function of mice was evaluated by the Basso Mouse Scale, Grid-walking test and Treadscan analysis. Brain MRI, anterograde virus tracer and immunofluorescence staining were applied to observe the tissue compatibility of SPIO in GRNs, trace GRNs’ projections and evaluate neurotransmitters’ expression in spinal cord respectively. Motor-evoked potentials and H reflex were collected for assessing the integrity of cortical spinal tract and the excitation of motor neurons in anterior horn.Results: (1) SPIO persisted in GRNs for a minimum of 24 weeks without inducing apoptosis of GRN cells, and degraded slowly over time. (2) MSS-enabled treadmill training dramatically improved locomotor performances of injured mice, and promoted cortico-reticulo-spinal circuit reorganization. (3) MSS-enabled treadmill training took superimposed roles through both activating GRNs to drive more projections of GRNs across lesion site and rebalancing neurotransmitters’ expression in anterior horn of lumbar spinal cord.Conclusion: These results indicate that selective MSS intervention of GRNs potentially serves as an innovative strategy to promote more spared fibers of GRNs across lesion site and rebalance neurotransmitters’ expression after spinal cord injury, paving the way for the structural remodeling of neural systems collaborating with exercise training, thus ultimately contributing to the reconstruction of cortico-reticulo-spinal circuit. Keywords: gigantocellular reticular nucleus, locomotion, magnetic stimulation, spinal cord injury, superparamagnetic iron oxide nanoparticles, treadmill training

Shaoqiu Zhang,1,&ast; Qun Zhang,2,&ast; Jian Wang,1,3,&ast; Yifan Pan,4 Zhiyi Zhang,5 Yu Geng,1 Bei Jia,1 Bing Tian,2 Yali Xiong,1 Xiaomin Yan,1 Jie Li,1,3– 5 Huali Wang,6 Rui Huang,1,3– 5 Chao Wu1,3– 5 1Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Infectious Diseases, Affiliated Zhongda Hospital of Southeast University, Nanjing, Jiangsu, People’s Republic of China; 3Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 6Department of General Practice, Nanjing Second Hospital, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Wu; Rui Huang, Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Tel +86-25-83105890, Fax +86-25-83307115, Email dr.wu@nju.edu.cn; doctor_hr@126.comBackground: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging epidemic infectious disease with high mortality rate. This study aimed to investigate the association of red blood cell distribution width (RDW) and mortality risk in hospitalized SFTS patients.Methods: Clinical data of SFTS patients was retrospectively collected from three hospitals between October 2010 and August 2022. Cox proportional hazards model was used to identity the risk factors for fatal outcome. The predictive value of RDW for fatal outcome was evaluated by the receiver operating characteristic (ROC) analysis and Kaplan–Meier methods.Results: Of 292 patients, the median age was 61.5 years. Non-survivors showed higher RDW value than survivors (13.6% vs.13.0%, P < 0.001). The mortality rate was 44.8% in patients with elevated RDW compared to 18.4% of patients with normal RDW, with a relative risk (RR) of 2.439. Elevated RDW was an independent risk factor of mortality (hazards ratio: 1.167, P = 0.019). Patients with elevated RDW had a higher cumulative mortality than patients with normal RDW. The area under the ROC curve (AUC) of RDW for the prediction of mortality was 0.690 (P < 0.001).Conclusion: Elevated RDW was associated with higher mortality risk for patients hospitalized for SFTS. RDW may be helpful for risk stratification in SFTS patients.Keywords: severe fever with thrombocytopenia syndrome, red blood cell distribution width, prognosis, survival

Haoyang Tian,1,&ast; Hui Chen,2,&ast; Xiaochun Yin,2 Meiyi Lv,3 Lingling Wei,1 Yuna Zhang,4 Shuhan Jia,5 Jingyuan Li,1 Hui Song1 1School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, People’s Republic of China; 2Department of Endodontics, Jinan Stomatological Hospital, Jinan, People’s Republic of China; 3Department of Pediatric Dentistry, Jinan Stomatological Hospital, Jinan, People’s Republic of China; 4Department of Stomatology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 5Department of Stomatology, Yancheng NO. 1 People’s Hospital, Yancheng, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Song; Jingyuan Li, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, People’s Republic of China, Tel +86-531-88382912, Fax +86-531-88382923, Email songhui@sdu.edu.cn; jingyuan_31@163.comIntroduction: Diabetes has been recognized as an independent risk factor for periodontitis. Increasing evidences indicate that hyperglycemia aggravates inflammatory response of human periodontal ligament cells (hPDLCs). Carbon monoxide-releasing molecule-3 (CORM-3) is a water-soluble compound that can release carbon monoxide (CO) in a controllable manner. CORM-3 has been shown the anti-inflammatory effect in different cell lineages.Methods: We stimulated periodontal ligament cells with LPS and high glucose. The expression of inflammatory cytokine was detected by ELISA. RT-qPCR, Western blot and immunofluorescence were used to detect the expression of TLR2, TLR4, RAGE and the activation of NF-κB pathway. We performed silencing and overexpression treatment of RAGE targeting the role of RAGE. We performed the immunostaining of paraffin sections of the periodontitis model in diabetes rats.Results: The results showed that CORM-3 significantly inhibited the expression of inflammatory cytokine in hPDLCs stimulated with LPS and high glucose. CORM-3 also inhibited LPS and high glucose-induced expression of RAGE/NF-κB pathway and TLR2/TLR4/NF-κB pathway. Silence of RAGE resulted in significantly decreased expression of proteins above. Overexpression of RAGE significantly enhanced the expression of these factors. CORM-3 abrogated the effect of RAGE partially. In animal model, CORM-3 suppressed the inflammatory response of periodontal tissues in experimental periodontitis of diabetic rats.Discussion: Our research proved CORM-3 reduced the inflammatory response via RAGE/NF-κB pathway and TLR2/TLR4/NF-κB pathway in the process of high glucose exacerbated periodontitis. These findings demonstrated the role of RAGE in the process of high glucose exacerbated periodontitis and suggested that CORM3 be a potential therapeutic strategy for the treatment of diabetes patients with periodontitis. Keywords: carbon monoxide-releasing molecules, periodontitis, diabetes, receptor for advanced glycation end products, lipopolysaccharide

Shuang Du,1,&ast; Ke Lin,2,&ast; Jing Li,3 Xin Zhou,4 Chaolan Wang,2 Jun Liu,3 Na Li,2 Jian Chen2 1Department of Rehabilitation Medicine, The First People’s Hospital of Jin Tang County, Chengdu, Sichuan, 610400, People’s Republic of China; 2Traditional Chinese Medicine Department, The First People’s Hospital of Jintang County, Chengdu, Sichuan, 610400, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Jintang County, Chengdu, Sichuan, 610400, People’s Republic of China; 4Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Chen, Traditional Chinese Medicine Department, The First People’s Hospital of Jintang County, Chengdu, Sichuan, 610400, People’s Republic of China, Tel +86-10-18908176456, Email chenjian792@163.comPurpose: COPD patients frequently have abnormal serum phosphorus levels. The objective of this study was to examine the correlation between serum phosphorus levels with hospital and 90-day mortality in critically ill patients with COPD.Patients and Methods: The MIMIC IV database was used for this retrospective cohort analysis. We extracted demographics, vital signs, laboratory tests, comorbidity, antibiotic usage, ventilation and scoring systems within the first 24 hours of ICU admission. Restricted cubic splines and multivariate cox regression analysis models were used to evaluate the connection between serum phosphorus with hospital and 90-day mortality. We assessed and classified various factors including gender, age, renal disease, severe liver disease, the utilization of antibiotics and congestive heart failure.Results: We included a total of 3611 patients with COPD, with a median age of 70.7 years. After adjusting for all other factors, we observed a significant positive association between serum phosphate levels with both hospital mortality (HR 1.19, 95% CI: 1.07– 1.31, p< 0.001) and 90-day mortality (HR 1.15, 95% CI: 1.06– 1.24, p< 0.001). Compared to the medium group (Q2 ≥ 3.15, < 4.0), the adjusted hazard ratios for hospital mortality were 1.47 (95% CI: 1.08– 2, p=0.013), and 1.31 (95% CI: 1.06– 1.61, p=0.013) for 90-day mortality in the high group (Q3≥ 4.0). Hospital mortality decreased at serum phosphate levels below 3.8 mg/dl (HR 0.664, 95% CI: 0.468– 0.943, p=0.022), but increased for both hospital (HR 1.312, 95% CI: 1.141– 1.509, p< 0.001) and 90-day mortality (HR 1.236, 95% CI: 1.102– 1.386, p< 0.001) when levels were above 3.8 mg/dl. Subgroup and sensitivity analyses yielded consistent results.Conclusion: In critical ill COPD patients, this study demonstrated a non-linear association between serum phosphate levels and both hospital and 90-day mortality. Notably, there was an inflection point at 3.8 mg/dl, indicating a significant shift in outcomes. Future prospective research is necessary to validate this correlation.Keywords: COPD, serum phosphate, mortality, MIMIC-IV, critically ill

Juan Li,1,&ast; Ziqing Gao,1,&ast; Ning Li,1 Ling Yao,1 Chao Liu,1 Che Xu,1 Xiaohui Ren,1 Aiqin Wang,1 Siqi Gao,2 Miao Wang,2 Xiang Gao,2 Kun Li,3 Jianfeng Wang1 1Department of Ophthalmology, First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, 233004, People’s Republic of China; 2School of Clinical Medicine, Bengbu Medical University, Bengbu, Anhui, 233004, People’s Republic of China; 3School of Life and Health Science, Anhui Science and Technology University, Fengyang, Anhui, 233100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kun Li; Jianfeng Wang, Email liangliang2419@126.com; wangjianfeng1969@163.comBackground: Drug therapy for eye diseases has been limited by multiple protective mechanisms of the eye, which can be improved using well-designed drug delivery systems. Mesoporous silica nanoparticles (MSNs) had been used in many studies as carriers of therapeutic agents for ocular diseases treatment. However, no studies have focused on ocular biosafety. Considering that MSNs containing tetrasulfur bonds have unique advantages and have drawn increasing attention in drug delivery systems, it is necessary to explore the ocular biosafety of tetrasulfur bonds before their widespread application as ophthalmic drug carriers.Methods: In this study, hollow mesoporous silica nanoparticles (HMSNs) with different tetrasulfur bond contents were prepared and characterized. The ocular biosafety of HMSN-E was evaluated in vitro on the three selected ocular cell lines, including corneal epithelial cells, lens epithelial cells and retinal endothelial cells (HREC), and in vivo by using topical eye drops and intravitreal injections.Results: In cellular experiments, HMSNs caused obvious S content-dependent cytotoxic effect. HMSNs with the highest tetrasulfur bond content (HMSN-E), showed the highest cytotoxicity among all the HMSNs, and HREC was the most vulnerable cell to HMSN-E. It was shown that HMSN-E could react with intracellular GSH to generate H2S and decrease intracellular GSH concentration. Treatment of HREC with HMSN-E increased intracellular ROS, decreased mitochondrial membrane potential, and induced cell cycle arrest at the G1/S checkpoint, finally caused apoptosis and necrosis of HREC. Topical eye drops of HMSN-E could cause corneal damage. The intravitreal injection of HMSN-E could induce inflammation in the vitreum and ganglion cell layers, resulting in vitreous opacities and retinal abnormalities.Conclusion: The incorporation of tetrasulfur bonds into HMSN can have toxic effects on ocular tissues. Therefore, when mesoporous silica nanocarriers are designed for ophthalmic pharmaceuticals, the ocular toxicity of the tetrasulfur bonds should be considered.Keywords: ophthalmic safety, hollow mesoporous silica nanoparticles, ophthalmic drug delivery, tetrasulfur bond

Jian Gao,1 Jiannan Li,2 Zengyou Luo,1 Hongyong Wang,3 Zhiming Ma1 1Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Colorectal and Anal Surgery, The Second Hospital of Jilin University, Changchun, People’s Republic of China; 3Department of Radiotherapy, The Second Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Zhiming Ma, Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Changchun, People’s Republic of China, Email mazhiming@jlu.edu.cnAbstract: Inflammatory bowel disease (IBD) is a chronic, non-specific inflammatory condition characterized by recurring inflammation of the intestinal mucosa. However, the existing IBD treatments are ineffective and have serious side effects. The etiology of IBD is multifactorial and encompasses immune, genetic, environmental, dietary, and microbial factors. The nanoparticles (NPs) developed based on specific targeting methodologies exhibit great potential as nanotechnology advances. Nanoparticles are defined as particles between 1 and 100 nm in size. Depending on their size and surface functionality, NPs exhibit different properties. A variety of nanoparticle types have been employed as drug carriers for the treatment of inflammatory bowel disease (IBD), with encouraging outcomes observed in experimental models. They increase the bioavailability of drugs and enable targeted drug delivery, promoting localized treatment and thus enhancing efficacy. Nevertheless, numerous challenges persist in the translation from nanomedicine to clinical application, including enhanced formulations and preparation techniques, enhanced drug safety profiles, and so forth. In the future, it will be necessary for scientists and clinicians to collaborate in order to study disease mechanisms, develop new drug delivery strategies, and screen new nanomedicines. Nevertheless, numerous challenges persist in the translation from nanomedicine to clinical application, including enhanced formulations and preparation techniques, enhanced drug safety profiles, and so forth. In the future, it will be necessary for scientists and clinicians to collaborate in order to study disease mechanisms, develop new drug delivery strategies, and screen new nanomedicines.Keywords: nanoparticles, inflammatory bowel diseases, targeted delivery, passive targeting, active targeting, drug delivery system

Xiaoqing Ma,&ast; Ruoying Zhang,&ast; Xinjun Cai, Yuying Lang, Huaichong Wang, Jinmeng Li Department of Pharmacy, Hangzhou Red Cross Hospital, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinmeng Li, Department of Pharmacy, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang Province, 310000, People’s Republic of China, Email jinmeng608@163.comAbstract: As a new generation of oxazolidinone antibacterial drugs, contezolid has been shown to have comparable or even stronger activity than linezolid and has a low risk of adverse reactions such as bone marrow suppression toxicity. However, there are currently very few clinical reports and pharmacokinetic data of contezolid on the anti-tuberculosis therapy. Therefore, we report a case study of the pharmacokinetic study of contezolid in elderly patients with renal insufficiency and tuberculosis. The patient’s condition improved after receiving an anti-tuberculosis regimen containing contezolid, with significant absorption of pleural effusion and lung plaques and nodules reduced. During the treatment, the patients’ platelet and white blood cell levels fluctuated within normal ranges, but hemoglobin levels significantly decreased and did not recover after discontinuation of contezolid. The trough concentration of contezolid and the concentration at 2, 4, 6, and 10 h after administration were 1.27μg/mL, 3.88μg/mL, 6.32μg/mL, 8.99μg/mL, and 3.14μg/mL, respectively. The plasma concentrations of bedaquiline and cycloserine during the treatment were also monitored. This study demonstrated the efficacy and safety of contezolid in the treatment of multidrug-resistant tuberculosis and analyzed its pharmacokinetic changes in elderly patients with renal insufficiency, providing a reference for the clinical use of contezolid.Keywords: contezolid, tuberculosis, plasma concentration, efficacy, safety

Wenze Han,1,2 Ran Zhang,1,2 Shuzhi Liu,1,2 Tong Zhang,1,2 Xuemin Yao,1,2 Yuxin Cao,1,2 Jiadi Li,1,2 Xiaoming Liu,1,2 Bing Li1,2 1Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, 030001, People’s Republic of China; 2Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Taiyuan, 030001, Shanxi, People’s Republic of ChinaCorrespondence: Xiaoming Liu; Bing Li, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, 030001, People’s Republic of China, Email lxming0912@163.com; libing1975vip@163.comAbstract: Whiskers are nanoscale, high-strength fibrous crystals with a wide range of potential applications in dentistry owing to their unique mechanical, thermal, electrical, and biological properties. They possess high strength, a high modulus of elasticity and good biocompatibility. Hence, adding these crystals to dental composites as reinforcement can considerably improve the mechanical properties and durability of restorations. Additionally, whiskers are involved in inducing the value-added differentiation of osteoblasts, odontogenic osteocytes, and pulp stem cells, and promoting the regeneration of alveolar bone, periodontal tissue, and pulp tissue. They can also enhance the mucosal barrier function, inhibit the proliferation of tumor cells, control inflammation, and aid in cancer prevention. This review comprehensively summarizes the classification, properties, growth mechanisms and preparation methods of whiskers and focuses on their application in dentistry. Due to their unique physicochemical properties, excellent biological properties, and nanoscale characteristics, whiskers show great potential for application in bone, periodontal, and pulp tissue regeneration. Additionally, they can be used to prevent and treat oral cancer and improve medical devices, thus making them a promising new material in dentistry.Keywords: whiskers, dentistry, growth mechanism, biomaterials

Huamin Zeng,1 Yiran Zhang,1,2 Ningyi Liu,1,3 Qingqing Wei,1,3 Fan Yang,1 Jie Li4 1Cancer Prevention and Treatment Institute of Chengdu, Department of Pathology, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, Sichuan, 611130, People’s Republic of China; 2School of Medical and Life Sciences, Chengdu University of traditional Chinese Medicine, Chengdu, Sichuan, 611137, People’s Republic of China; 3School of Basic Medicine, North Sichuan Medical College, Nanchong, Sichuan, 637007, People’s Republic of China; 4Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, People’s Republic of ChinaCorrespondence: Jie Li, Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, People’s Republic of China, Tel +86 183 0831 2997, Email kerald2lj@126.com Fan Yang, Cancer Prevention and Treatment Institute of Chengdu, Department of Pathology, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, Sichuan, 611130, People’s Republic of China, Tel +86 136 7819 2175, Email yangfan03@126.comAbstract: Introduction of exogenous genes into target cells to overcome various tumor diseases caused by genetic defects or abnormalities and gene therapy, a new treatment method, provides a promising strategy for tumor treatment. Over the past decade, gene therapy has made exciting progress; however, it still faces the challenge of low nucleic acid delivery and release efficiencies. The emergence of nonviral vectors, primarily nanodelivery and release systems (NDRS), has resulted in a historic breakthrough in the application of gene therapy. NDRS, especially stimulus-responsive NDRS that can respond in a timely manner to changes in the internal and external microenvironment (eg, low pH, high concentration of glutathione/reactive oxygen species, overexpressed enzymes, temperature, light, ultrasound, and magnetic field), has shown excellent loading and release advantages in the precision and efficiency of tumor gene therapy and has been widely applied. The only disadvantage is that poor transfection efficiency limits the in-depth application of gene therapy in clinical practice, owing to the presence of biological barriers in the body. Therefore, this review first introduces the development history of gene therapy, the current obstacles faced by gene delivery, strategies to overcome these obstacles, and conventional vectors, and then focuses on the latest research progress in various stimulus-responsive NDRS for improving gene delivery efficiency. Finally, the future challenges and prospects that stimulus-responsive NDRS may face in clinical application and transformation are discussed to provide references for enhancing in-depth research on tumor gene therapy.Keywords: stimulus-responsive NDRS, gene delivery, tumor treatment, delivery and release efficiency, tumor microenvironment, physiological barrier, efficacy improvement strategies

Jialin Gu,1,2,&ast; Hailan Wu,1,3,&ast; Wanjing Diao,1,&ast; Yi Ji,1 Jianyue Li,1 Jiege Huo1 1Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210028, People’s Republic of China; 2Department of Traditional Chinese medicine, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People’s Republic of China; 3Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210016, People’s Republic of China&ast;These authors contribute equally to this workCorrespondence: Jiege Huo; Jianyue Li, Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, 100 Cross Street, Maigaoqiao, Nanjing, Jiangsu, 210028, People’s Republic of China, Email huojiege@jsatcm.com; tnt2vb@126.comObjective: To examine potential factors affecting sleep duration and explore its association with the risk of mortality among adults in the United States.Methods: The study population consisted of adults aged 26 to 79 years who participated in the National Health and Nutrition Examination Survey (NHANES) conducted from 2007 to 2016. Sleep duration was classified into three categories: short (< 7 hours), optimal (7– 8 hours), and long (≥ 9 hours). The associations between sleep duration and both all-cause mortality and cause-specific mortality (including heart disease, tumors, cerebrovascular disease, and others) were examined in the overall population and subgroups using weighted Cox regression models. Dose-response associations between sleep duration and risk of all-cause mortality were explored using restricted cubic spline (RCS) analyses. Additionally, a multinomial logistic regression analysis was conducted to investigate potential factors that influence sleep duration in adults.Results: The study included a total of 24,141 subjects, with a population-weighted mean age of 48.93 years. Over 30% of the subjects exhibited unhealthy sleep habits. Fully adjusted models revealed that both short sleep duration (HR=1.169, 95% CI 1.027– 1.331) and long sleep duration (HR=1.286, 95% CI 1.08– 1.531), were associated with an increased risk of all-cause mortality. The RCS curves showed a U-shaped relationship between sleep duration and risk of all-cause mortality. Subgroup analyses showed a significant association between poor sleep patterns and all-cause mortality among adults aged 26– 64 years, males, and non-Hispanic whites. Furthermore, multinomial logistic regression identified several predictors associated with short and long sleep durations.Conclusion: Both short and long sleep duration are associated with an increased risk of all-cause mortality, with a U-shaped dose-response relationship. It is imperative to implement appropriate primary prevention strategies aimed at monitoring and providing health education to populations at risk of developing unhealthy sleep patterns.Keywords: sleep duration, mortality, adults, association, NHANES

Yu-Kai Li,1,&ast; Song Wu,2,&ast; Yu-Shan Wu,3,&ast; Wei-Hu Zhang,4,&ast; Yan Wang,5,&ast; Yue-Hua Li,1,&ast; Qiang Kang,1,&ast; Song-Quan Huang,1,&ast; Kai Zheng,1 Gai-Ming Jiang,1 Qing-Bo Wang,1 Yu-Bo Liang,1 Jin Li,1 Yawhan Lakang,1 Chen Yang,1 Jing Li,1 Jia-Ping Wang,4 Xiang Kui,5 Yang Ke1,6,7 1Department of Hepato-Biliary-Pancreatic, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 2Preventive Medicine Division, School of Life Science, Anhui University of Chinese Medicine, Hefei, AH, 230012, People’s Republic of China; 3The Second Clinical Medical College, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 4Department of Radiology, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 5Department of Pathology, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 6Department of Surgical Education and Research, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 7Yunnan Yunke Bio-Technology Institution, Kunming, YN, 650201, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Kui, Department of Pathology, the Second Affiliated Hospital, Kunming Medical University, No. 374 Kunrui Road, Wuhua District, Kunming, YN, 650101, People’s Republic of China, Tel +8613708729335, Email kuixiang@foxmail.com Yang Ke, Department of Hepato-Biliary-Pancreatic, the Second Affiliated Hospital, Kunming Medical University, No. 374 Kunrui Road, Wuhua District, Kunming, YN, 650101, People’s Republic of China, Tel +8615808875159, Email keyang1218@126.comBackground: The dominant artery blood supply is a characteristic of hepatocellular carcinoma (HCC). However, it is not known whether the blood supply can predict the post-hepatectomy prognosis of patients with HCC. This retrospective study investigated the prognostic value of the portal venous and arterial blood supply estimated on triphasic liver CT (as a portal venous coefficient, PVC, and hepatic arterial coefficient, HAC, respectively) in patients with HCC following hepatectomy.Methods: HCC patients who were tested by triphasic liver CT 2 weeks before hepatectomy and received R0 hepatectomy at the Second Affiliated Hospital, Kunming Medical University between January 1, 2016 and December 31, 2020, were retrospectively screened. Their PVC and HAC, and other variables were analyzed for the prediction of overall survival (OS) and recurrence-free survival (RFS) using the least absolute shrinkage and selection operator and Cox proportional hazard regression models.Results: Four hundred and nineteen patients (53.2 ± 10.6 years of age and 370 men) were evaluated. A shorter OS was independently associated with higher blood albumin and total bilirubin grade [hazard ratio (HR) 2.020, 95% confidence interval (CI) 1.534– 2.660], higher Barcelona Clinic Liver Cancer (BCLC) stage (HR 1.514, 95% CI 1.290– 1.777), PVC ≤ 0.386 (HR 1.628, 95% CI 1.149– 2.305), and HAC > 0.029 (HR 1.969, 95% CI 1.380– 2.809). A shorter RFS was independently associated with male (HR 1.652, 95% CI 1.005– 2.716), higher serum α-fetoprotein ≥ 400 ng/mL (HR 1.672, 95% CI 1.236– 2.263), higher BCLC stage (HR 1.516, 95% CI 1.300– 1.768), tumor PVC ≤ 0.386 (HR 1.641, 95% CI 1.198– 2.249), and tumor HAC > 0.029 (HR 1.455, 95% CI 1.060– 1.997).Conclusion: Tumor PVC or HAC before hepatectomy is valuable for independently predicting postoperative survival of HCC patients. Keywords: blood supply, computed tomography, hepatectomy, hepatocellular carcinoma, recurrence, survival

Fangfang Fan,1,2,&ast; Zhe Liang,1,2,&ast; Zhihao Liu,1 Pengfei Sun,1 Lihua Hu,1 Jia Jia,1,2 Yan Zhang,1,2 Jianping Li1,2 1Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of China; 2Institute of Cardiovascular Disease, Peking University First Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianping Li, Department of Cardiology & Institute of Cardiovascular Disease, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of China, Email lijianping03455@pkufh.comPurpose: Early identification of new residual risk factors for coronary heart disease (CHD) is warranted. In this study, we aim to investigate the association between the serine concentration, an important amino acid in one-carbon metabolism, and CHD in Chinese hospitalized patients.Patients and Methods: This case–control study included 428 case–control pairs comprising patients with CHD with a maximum coronary artery stenosis degree of > 70% and controls with stenosis of < 30%. The individuals were matched by age, sex, and date of coronary angiography at Peking University First Hospital from January 1, 2016, to December 31, 2019. Conditional logistic regression was used to investigate the associations between the serine concentration and CHD.Results: Patients with CHD were aged 63.48 ± 10.38 years, and 43.73% were male. Compared with controls, patients with CHD had a slightly lower serine concentration (13.35 ± 4.20 vs 13.77 ± 4.08 μg/mL), but the difference was not significant. In the multivariable conditional logistic regression analysis, for every 1 μg/mL increase in serine concentration, the odds of CHD decreased by 6% (95% confidence interval [CI] 0.90– 0.99; P = 0.010). Patients with a serine concentration of ≥ 13.41 μg/mL had a lower CHD risk than those with a serine concentration of < 13.41 μg/mL (odds ratio [OR] 0.57, 95% CI 0.39– 0.84; P = 0.004). Subgroup analyses showed that sex interacted with the relationship between serine concentration and CHD (Pinteraction = 0.039), which was more significant in males (OR 0.93, 95% CI 0.87– 0.98; P = 0.013) than in females.Conclusion: This study observed an inverse association between the serine concentration and CHD prevalence in Chinese hospitalized patients, which revealed that serine might play a protective role in CHD.Keywords: serine, coronary heart disease, case–control, one-carbon metabolism

Yatian Jia,1,2 Qian Zhang,1– 3 Yihua Zhang,2 Hui Wang,1,2 Qingmei Niu,1,2 Ruifang Zhu,4 Jia Li,1 Wen Fan,1 Yuexing Zhang2 1Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, People’s Republic of China; 2School of Nursing, Shanxi University of Chinese Medicine, Jinzhong, People’s Republic of China; 3School of Nursing/Research Center of Dietary Therapy Technology, Shanxi Medical University, Taiyuan, People’s Republic of China; 4Editorial Office, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Qian Zhang, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Xiaodian District, Taiyuan, Shanxi, People’s Republic of China, Email zhangqian@d.sxmu.edu.cnBackground: Hyperlipidemia has been demonstrated to be an autonomous predictor of numerous cardiovascular and cerebrovascular ailments, and research indicates that polyphenols have preventive and therapeutic effects on hyperlipidemia. Nevertheless, the impact of polyphenol-rich foods on blood lipids and oxidative stress status in patients with hyperlipidemia remains inconclusive.Objective: To examine the impact of polyphenol-rich foods on lipid levels and oxidative stress in individuals with hyperlipidemia.Methods: To retrieve papers published from the establishment of the database through October 9, 2023, eight databases were searched: the Chinese National Knowledge Infrastructure, the China Biomedical Literature Database, the Wanfang Database, the China Science and Technology Journal Database, PubMed, the Cochrane Library, Embase, and the Web of Science. The quality of include studies was assessed using the Cochrane Risk of Bias in Randomized Trials tool, v2.Results: The study involved 13 surveys encompassing 640 patients diagnosed with hyperlipidemia. The scope of the food surveys included 12 commonly consumed food groups and medicinal and food homologous substances. All 13 studies reported the effects of polyphenol-rich foods on blood lipids, with significant improvements observed in blood lipid levels for 9 types of foods. Eight studies examined the impact on oxidative stress, and six foods demonstrated a significant reduction in oxidative stress levels. The observed effects were found to be influenced by factors such as dosage, duration of intervention, and gender.Conclusion: Foods abundant in polyphenols play a crucial role in the prevention and treatment of hyperlipidemia by counteracting oxidative stress and regulating metabolic disorders. The confirmation of certain positive effects by several studies notwithstanding, discrepancies in results arise from various factors, necessitating further large-scale, prospective, well-designed randomized controlled studies to address this issue.Keywords: polyphenols, hyperlipidemia, blood lipids, oxidative stress, systematic review