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Jianni Cong,1,&ast; Jiahuang Chi,2,&ast; Junli Zeng,3 Yilan Lin2 1School of Health Management, Binzhou Medical University, Shandong, People’s Republic of China; 2Department of Chronic and Non-Communicable Diseases Control and Prevention, Xiamen Center for Disease Control and Prevention, Xiamen, People’s Republic of China; 3Department of Respiratory Center, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yilan Lin, Email linyl254@163.comObjective: To analyze the trends of lung cancer incidence and mortality in Xiamen from 2011 to 2020 and provide some clues for the lung cancer prevention and control.Methods: The data was obtained from the Xiamen City Cancer Register in Fujian Province, China. The data was updated on Sep 30, 2023. The codes of C33-C34 were used to identify the lung cancer. The newly diagnosed lung cancer patients during the period of 2011– 2020 in Xiamen City were included in the evaluation of incidence and mortality and Cox analysis.Results: A total of 11408 lung cancer patients were enrolled. The crude incidence rate was 52.78 per 100000 and the age-standardized incidence rate (ASIWR) was 40.67 per 100000 from 2011 to 2020. Both the crude incidence rate of lung cancer (AAPC =5.92, P value < 0.001) and ASIWR (AAPC = 4.93, P value < 0.001) showed increasing trends. The crude incidence rate in female increased 4.90 times faster as that in male (AAPC: 12.34/2.52). The crude mortality rate and the age-standardized mortality rate (ASMWR) were 37.25 per 100000 and 28.30 per100000. The 5-year age-standardized relative survival rate (ARS) was 18.62% (95% CI: 17.63– 19.67%). The 5-year ARS was higher in women than men (26.35% vs 15.28%) and higher in urban than rural areas (21.44% vs 11.96%). Patients with lower education levels had significantly lower ARS than those with higher education (14.66% vs 31.53%). The 5-year ARS improved notably from 2016– 2020 compared to 2011– 2015 (22.23% vs 13.21%). Farmers had the lowest ARS among occupations [13.34% (95% CI:11.93– 14.92%)]. There were all increasing trends in 1-year, 3-year, 5-year, and 10-year ARS rates between 2011 and 2020 (all P values of AAPC< 0.05).Conclusion: Lung cancer incidence in Xiamen increased, while mortality decreased with improved survival. Developing more perfect need to consider the differences in the social environment and other factors.Keywords: lung cancer, incidence, mortality, trend, survival analyze

Yaqing Lin,1,&ast; Xuemei Ling,2,3,&ast; Linghua Li,2,&ast; Ruolei Xin,4 Fengyu Hu,1 Junbin Li,3 Jiaojiao Li,1 Feng Li,1,5 Yun Lan1 1Institute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Guangzhou Institute of Clinical Infectious Diseases, Infectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Guangdong Center for Diagnosis and Treatment of AIDS, Guangzhou, People’s Republic of China; 4Institute of AIDS/STD Prevention and Control, Beijing Center for Disease Prevention and Control, Beijing, People’s Republic of China; 5Scientifc Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Li; Yun Lan, Email gz8h_lifeng@126.com; lanyun.vip@126.comBackground: The capsid inhibitor (CAI) lenacapavir (LEN) was approved for use in 2022, yet there are few reports about its drug resistance mutations (DRMs) and sensitivity.Purpose: To delineate the prevalence of CAI DRMs and drug susceptibility among HIV-1 infected individuals living in Guangdong, China.Patients and Methods: A total of 1035 individuals with HIV-1 infection, including 660 highly Active Anti-Retroviral Therapy (HAART) naive individuals and 375 hAART experienced individuals whose protease (PR)/ reverse transcriptase (RT) fragments were amplified successfully during drug resistance surveillance between October 2021 and December 2023, were randomly included in this study. The entire HIV-1 gag gene was amplified from plasma in LEN-naive individuals with or without antiretroviral therapy. The epidemiological and demographic information of the enrolled individuals were collected. The Stanford HIV Drug Resistance Database HIVdb program for Capsid was used to interpret the CAI DRMs and the LEN susceptibility.Results: Among 1035 samples, 805 gag sequences were amplified, sequenced and assembled successfully from 518 hAART drugs naive individuals and 287 hAART drugs experienced individuals. Among them, 0.50% (4/805) carried at least one CAI DRM, of which 0.19% (1/518) from HAART naive individuals and 1.05% (3/287) from HAART experienced individuals. Among the individuals with CAI DRMs, two patients carried CAI major mutations (Q67H) conferring intermediate resistance to LEN and two patients carried CAI accessory mutation (T107A) conferring low level resistance to LEN.Conclusion: Extremely low prevalence of CAI DRMs was detected among people living with HIV (PLWH) in Guangdong, China. Our observations indicate that LEN application may be promising when used in clinical practice in China. Before the administration of LEN, there is no need to consider detecting CAI mutations in PLWH through DRM examination for the time being.Keywords: HIV-1, capsid inhibitor, lenacapavir, drug resistance mutation, Guangdong

Yan Jiang,1,&ast; Baolin Luo,2,&ast; Wen Lu,1 Yaqin Chen,1 Yanchun Peng,2 Liangwan Chen,3,4 Yanjuan Lin2,3 1School of Nursing, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Department of Nursing, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 3Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China; 4Fujian Provincial Special Reserve Talents Laboratory, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liangwan Chen, Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China, Email fjxhlwc@163.com Yanjuan Lin, Department of Nursing, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of China, Email fjxhyjl@163.comPurpose: The Aggregate Index of Systemic Inflammation (AISI) has emerged as a novel marker for inflammation and prognosis, but its role in patients with acute myocardial infarction has not been studied. Therefore, this study aimed to investigate the impact of different AISI levels on the clinical outcomes of patients with acute myocardial infarction.Patients and Methods: This study was a retrospective study, including 1044 patients with acute myocardial infarction (AMI) who were treated at the Fujian Medical University Affiliated Union Hospital, China from May 2017 to December 2022. The patients were divided into high and low AISI groups based on the median value (Q1 Group, ≤ 416.15, n=522; Q2 Group, ≥ 416.16, n=522), and the differences in baseline characteristics and clinical outcomes between the two groups were analyzed. The primary outcome included major adverse cardiovascular and cerebrovascular events (MACCEs), while the secondary outcomes included contrast-induced nephropathy (CIN) risk and all-cause rehospitalization rate.Results: The findings of the single-factor analysis suggest that a significant association between high AISI levels and the occurrence of MACCEs in AMI patients. After adjusting for confounding factors, the results indicated that compared to Q1, patients in the Q2 group had a higher risk of all-cause mortality [adjusted odds ratio (aOR) 4.64; 95% CI 1.37– 15.72; p=0.032], new-onset atrial fibrillation (aOR 1.75; 95% CI 1.02– 3.00; p=0.047), and CIN (aOR 1.75; 95% CI 1.02– 3.01; p=0.043), with all differences being statistically significant.Conclusion: In the population of AMI patients, an elevated AISI level is significantly associated with an increased risk of cardiovascular death and can serve as an early marker for adverse prognosis.Keywords: acute myocardial infarction, inflammation index, clinical outcomes, MACCEs

Xia Yuan,1,2,&ast; Shenmin Wan,1,2,&ast; Wenshuo Wang,2,3 Yihong Chen,1,2 Ying Lin1 1Department of Nursing, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Heart Valve Engineering Technology Research Center, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yihong Chen; Ying Lin, Department of Nursing, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Tel +86 21-64041990, Email chen.yihong@zs-hospital.sh.cn; lin.ying@zs-hospital.sh.cnPurpose: Individualized anticoagulation therapy is a major challenge for patients after heart valve replacement. Mobile applications assisted by Artificial intelligence (AI) have great potential to meet the individual needs of patients. The study aimed to develop an AI technology-assisted mobile application (app) for anticoagulation management, understand patients’ acceptance of such applications, and determine its feasibility.Methods: After using the mobile application for anticoagulation management for 2 weeks, patients, doctors, and nurses rated its usability using the System Usability Scale (SUS). Additionally, semi-structured interviews were conducted with some patients, doctors, and nurses to gain insights about their thoughts and suggestions regarding the procedure.Results: The study comprised 80 participants, including 38 patients, 18 doctors, and 24 nurses. The average SUS score for patients was 82.37± 5.45; for doctors, it was 84.17± 5.82; and for nurses, it was 81.88± 6.44. This means the patients, physicians, and nurses rated the app highly usable. Semi-structured interviews were conducted on the app’s usability with 18 participants (six nurses, three physicians, and nine patients). The interview results revealed that patients found the application of anticoagulation management simple and convenient, with high expectations for a precise dosage recommendation of anticoagulant drugs. Some patients expressed concerns regarding personal information security. Both doctors and nurses believed that elderly patients needed assistance from young family members to use the app and that it could improve patients’ anticoagulant self-management ability. Some nurses also mentioned that the use of the app brought great convenience for transitional care.Conclusion: This study confirmed the feasibility of using an AI technology-assisted mobile application for anticoagulation management in patients after heart valve replacement. To further develop this application, challenges lie in continuously improving the accuracy of recommended drug doses, obtaining family support, and ensuring information security.Keywords: anticoagulation management, artificial intelligence (AI) technology, mobile application, heart valve replacement, warfarin

Guolin Zhao,1,2 Zhijun Wang,1,2 Jun Zhang,1,2 Yuan Lin,1,2 Tang Zhou,1,2 Kaili Liu,1,2 Changyong Yang,1 Cheng Liao1 1Department of Preclinical Research and Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, Jiangsu, People’s Republic of China; 2Department of Preclinical Research and Development, Shanghai Shengdi Pharmaceutical Co., Ltd., Shanghai, People’s Republic of ChinaCorrespondence: Changyong Yang; Cheng Liao, Department of Preclinical Research and Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd., Lianyungang, Jiangsu, 222000, People’s Republic of China, Tel/Fax +86 021-61629291 ; +86 021-61063826, Email changyong.yang@hengrui.com; cheng.liao@hengrui.comBackground: Interleukin (IL)-4 and IL-13 are critical pathogenic factors for type 2 inflammation-related allergic diseases, sharing the mutual receptor subunit IL-4Rα. However, it was ineffective for certain type 2 inflammation diseases by targeting IL-4, IL-13 ligand alone or both in clinical studies. The work presented herein aimed to evaluate the preclinical efficacy and pharmacokinetics profile of a novel monoclonal antibody against IL-4Rα, SHR-1819, as a promising therapy for type 2 inflammation diseases.Methods: SHR-1819 was generated through immunization by C57BL/6 mice with recombinant hIL-4Rα protein, followed by humanization and affinity maturation. Then, its binding properties with IL-4Rα were determined using surface plasmon resonance (SPR) and ELISA. In vitro inhibitory effects of SHR-1819 were assessed on hIL-4-/hIL-13-induced cell proliferation and signal transducer and activator of transcription 6 (STAT6) signaling activation. In vivo efficacy of SHR-1819 was evaluated in several type 2 inflammatory diseases models, including asthma, atopic dermatitis (AD), and allergic rhinitis (AR) by using hIL-4/hIL-4Rα transgenic mice. Furthermore, the pharmacokinetic (PK) profiles of SHR-1819 were characterized.Results: SHR-1819 showed high binding affinity to human IL-4Rα and effectively blocked IL-4Rα at sub-nanomolar concentration. In vitro assays indicated that SHR-1819 significantly inhibited TF-1 cell proliferation and STAT6 activation induced by hIL-4/hIL-13. In the asthma model, SHR-1819 could reduce airway hyperresponsiveness, decrease serum IgE levels, and alleviated inflammatory lung cell infiltration. In the AD model, SHR-1819 could significantly alleviate inflammatory and skin symptoms. In the AR model, it could remarkably decrease the frequencies of nasal rubbing and sneezing, and inflammatory cell infiltration in nasal tissues. These in vivo efficacy studies demonstrated the therapeutic potential of SHR-1819 in preclinical disease models. Moreover, subcutaneous administration of SHR-1819 exhibited favorable bioavailability in mice.Conclusion: The results supported SHR-1819 as a promising preclinical candidate for the treatment of type 2 inflammatory diseases, including asthma, AD and AR.Keywords: type 2 inflammatory diseases, IL-4Rα, IL-4, IL-13

Jing Wang,1,&ast; Lei Tian,2,&ast; Weilong Zhang,1,&ast; Shuhan Tang,1 Wei Zhao,1 Yu Guo,1 Chaoling Wu,1 Yuansheng Lin,1 Xiaoyan Ke,1 Hongmei Jing1 1Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Health Management Center, Peking University Third Hospital, Beijing, 100191, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyan Ke; Hongmei Jing, Email xykbysy@163.com; hongmeijing@bjmu.edu.cnBackground: The application of rituximab has significantly enhanced the overall survival rates in patients with diffuse large B-cell lymphoma (DLBCL). Regrettably, a significant number of patients still progress to relapse/refractory DLBCL (rrDLBCL).Methods: Herein, we employed targeted sequencing of 55 genes to investigate if gene mutations could predict the progression to rrDLBCL. Additionally, we compared the mutation profiles at the time of DLBCL diagnosis with those found in rrDLBCL cases.Results: Our findings highlighted significantly elevated mutation frequencies of TP53, MEF2B and CD58 in diagnostic biopsies from patients who progressed to relapse or refractory disease, with CD58 mutations exclusively observed in the rrDLBCL group. In assessing the predictive power of mutation profiles for treatment responses in primary DLBCL patients, we found that the frequency of CARD11 mutations was substantially higher in non-response group as compared with those who responded to immunochemotherapy. In addition, we revealed mutations in HIST2H2AB, BCL2, NRXN3, FOXO1, HIST1H1C, LYN and TBL1XR1 genes were only detected in initial diagnostic biopsies, mutations in the EBF1 gene were solely detected in the rrDLBCL patients.Conclusion: Collectively, this study elucidates some of the genetic mechanisms contributing to the progression of rrDLBCL and suggests that the presence of CD58 mutations might serve as a powerful predictive marker for relapse/refractory outcomes in primary DLBCL patients.Keywords: targeted sequencing, mutation profile, relapse/refractory disease, diffuse large B-cell lymphoma

Weitang Sun,1 Jingbin Zhong,1 Buyun Gao,2 Jieling Feng,1 Zijie Ye,1 Yueling Lin,3 Kelan Zhang,3 Wenqi Su,3 Shibo Zhu,1 Yinghua Li,4 Wei Jia1 1Department of Pediatric Urology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2School of Pharmacy, Fudan University, Shanghai, People’s Republic of China; 3Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 4Center Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Wei Jia, Email jiawei198044@hotmail.comPurpose: Hydroxyapatite-based nanoparticles have found diverse applications in drug delivery, gene carriers, diagnostics, bioimaging and tissue engineering, owing to their ability to easily enter the bloodstream and target specific sites. However, there is limited understanding of the potential adverse effects and molecular mechanisms of these nanoparticles with varying geometries upon their entry into the bloodstream. Here, we used two commercially available hydroxyapatite nanoparticles (HANPs) with different geometries (less than 100 nm in size each) to investigate this issue.Methods: First, the particle size, Zeta potential, and surface morphology of nano-hydroxyapatite were characterized. Subsequently, the effects of 2~2000 μM nano-hydroxyapatite on the proliferation, migration, cell cycle distribution, and apoptosis levels of umbilical vein endothelial cells were evaluated. Additionally, the impact of nanoparticles of various shapes on the differential expression of genes was investigated using transcriptome sequencing. Additionally, we investigated the in vivo biocompatibility of HANPs through gavage administration of nanohydroxyapatite in mice.Results: Our results demonstrate that while rod-shaped HANPs promote proliferation in Human Umbilical Vein Endothelial Cell (HUVEC) monolayers at 200 μM, sphere-shaped HANPs exhibit significant toxicity to these monolayers at the same concentration, inducing apoptosis/necrosis and S-phase cell cycle arrest through inflammation. Additionally, sphere-shaped HANPs enhance SULT1A3 levels relative to rod-shaped HANPs, facilitating chemical carcinogenesis-DNA adduct signaling pathways in HUVEC monolayers. In vivo experiments have shown that while HANPs can influence the number of blood cells and comprehensive metabolic indicators in blood, they do not exhibit significant toxicity.Conclusion: In conclusion, this study has demonstrated that the geometry and surface area of HANPs significantly affect VEC survival status and proliferation. These findings hold significant implications for the optimization of biomaterials in cell engineering applications.Keywords: hydroxyapatite nanoparticle, circulatory system, biocompatibility, survival, proliferation

Na Li,1,&ast; Yue-xiang Ren,2,&ast; Heng-ming Ye,1,3 Ying Lin,4 Qiang Liu,5 Jiao Wang,1 Ze-fang Ren,1 Lin Xu1,6,7 1The School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Public Health Service Center of Bao’an District, Shenzhen, People’s Republic of China; 4The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 5Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 6School of Public Health, the University of Hong Kong, Hong Kong; 7Institute of Applied Health Research, University of Birmingham, Birmingham, UK&ast;These authors contributed equally to this workCorrespondence: Ze-fang Ren; Lin Xu, School of Public Health, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou, 510080, People’s Republic of China, Tel +0086-20-87332577 ; Tel +0086-20- 87335523, Fax +011-86-20-87332577, Email renzef@mail.sysu.edu.cn; xulin27@mail.sysu.edu.cnPurpose: Chlamydia trachomatis (C. trachomatis) is associated with several gynecological tumors; yet its prognostic role in breast cancer remains unclear. Thus, we investigated the prognostic role of anti-C. trachomatis immunoglobulin G (IgG) in breast cancer patients and the modification effects of pro-inflammatory cytokines.Methods: The serum levels of C. trachomatis IgG and four pro-inflammatory cytokines were measured. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), including product terms to assess the modification effects of pro-inflammatory cytokines on the association between C. trachomatis IgG and breast cancer prognosis.Results: From 2008 to 2018, 1121 breast cancer patients were recruited and followed up until December 31, 2021, with a median follow-up time of 63.91 months (interquartile range: 39.16– 90.08 months). Patients positive for C. trachomatis IgG showed HRs of 1.09 (95% CI, 0.67– 1.78) for overall survival (OS) and 1.24 (0.87– 1.78) for progression-free survival (PFS), compared to those who were negative. These associations became statistically significant in women aged 50 years or younger (HR=1.43, 95% CI=0.79– 2.58 for OS; HR=1.79, 95% CI=1.16– 2.77 for PFS). Positive C. trachomatis IgG serology was associated with adverse prognostic effects among patients with higher levels of pro-inflammatory cytokines (IL-6, TNF-α, IL-8, and IL-1β), but with favorable prognostic effects for those with low levels. These interactions were particularly significant in those aged 50 years or younger.Conclusion: In breast cancer patients younger than 50 years of age or with higher levels of pro-inflammatory cytokines, C. trachomatis infection appeared to have a negative prognostic impact. These findings highlight the significance of C. trachomatis in predicting prognosis and personalized therapy for breast cancer patients.Keywords: Chlamydia trachomatis, breast cancer, prognosis, pro-inflammatory cytokines

Yibin Lin,1,2 Lehua Liu,1 Siyang Lu,1 Linqi Fan,1 Huaqi Hu,1 Xuanyin Wang,1 Jichao Zhu,3 Xinhua Qiang,4 Jie He,5 Hongchang Zhou,1,2,6 Shengwen Shao,1,6 Gaoming Zheng7 1School of Medicine, Huzhou University, Huzhou, 313000, People’s Republic of China; 2Key Laboratory for Precise Prevention and Control of Major Chronic Diseases, Huzhou University, Huzhou, 31300, People’s Republic of China; 3Clinical Laboratory, Huzhou Central Hospital, Huzhou, 313000, People’s Republic of China; 4Clinical Laboratory, First People’s Hospital Affiliated to Huzhou University, Huzhou, 313000, People’s Republic of China; 5Infectious Diseases Department, First People’s Hospital Affiliated to Huzhou University, Huzhou, 313000, People’s Republic of China; 6Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, Huzhou University, Huzhou, 313000, People’s Republic of China; 7Clinical Laboratory, Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310015, People’s Republic of ChinaCorrespondence: Gaoming Zheng; Shengwen Shao, Email zheng151031@sina.com; shaoshw@zjhu.edu.cnBackground: Bacillus cereus is a common bacterium found in the environment. Some strains can cause food poisoning, and very few can cause clinically severe infections, leading to death. Here, we characterized the genome sequence of B. cereus LIN78 isolated from teeth with deep caries and compared it with those of 25 other related species.Methods: Third-generation sequencing technology, bacteriological analyses, biochemistry, and mass spectrometry were applied to characterize the drug-resistance genes and virulence factors of B. cereus LIN78.Results: The complete genome sequence of B. cereus Lin78 consists of 5647 genes distributed on a circular chromosome, a 393 kbp plasmid, and 928 pseudogenes (37.4% of whole-genome DNA). The LIN78 genome contains 14 sets of 16s, 23s, and 5s ribosomal RNA operons; 106 tRNA genes, one tmRNA, 12 genomic islands, six prophases, 64 repeats; 37 antibiotic-resistant genes; and 1119 putative virulence genes, including enterotoxins and cytolysins. The B. cereus LIN78 genome carries multiple copies of non-ribosomal polypeptide synthetase (NRPS) and post-translationally modified peptides (RiPPs). Phylogenetic analysis of the 26 B. cereus strains showed that B. cereus LIN78 is evolutionarily closely related to B. thuringiensis ATCC 10792 and B. cereus ATCC 14579.Conclusion: The newly isolated B. cereus carries many virulence genes, including enterotoxins and hemolysins, similar to B. anthracis, and multiple antibiotic resistance genes. These findings suggest that the strain has a potential risk of causing disease. Our studies are vital for further exploration of the evolution of B. cereus, its pathogenic mechanisms, and the control and treatment of bacterial infections.Keywords: bacillus cereus, whole-genome DNA sequencing, virulence factor, drug resistance gene, human teeth

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

Achieving high material perfection in aluminum (Al) films and their associated Al/AlOx heterostructures is essential for enhancing the coherence time in superconducting quantum circuits. We grew Al films with thicknesses ranging from 3 to 30 nanometers (nm) epitaxially on sapphire substrates using molecular beam epitaxy (MBE). An integral aspect of our work involved electron-beam (e-beam) evaporation to directly deposit aluminum oxide (Al2O3) films on the freshly grown ultrathin epitaxial Al films in an ultra-high-vacuum (UHV) environment. This in situ oxide deposition is critical for preventing the oxidation of parts of the Al films, avoiding the formation of undesired native oxides, and thereby preserving the nm-thick Al films in their pristine conditions. The thicknesses of our Al films in the study were accurately determined; for example, coherence lengths of 3.0 and 20.2 nm were measured in the nominal 3.0 and 20 nm thick Al films, respectively. These Al films were epitaxially grown on sapphire substrates, showing an orientational relationship, denoted as Al (111) ⟨ 2 1 ¯ 1 ¯ ⟩ ∥ sapphire (0001) [ 2 1 ¯ 1 ¯ 0 ]. The Al/sapphire interface was atomically ordered without any interfacial layers, as confirmed by in situ reflection high-energy electron diffraction (RHEED) and cross-sectional scanning transmission electron microscopy (STEM). All sample surfaces exhibited smoothness with a roughness in the range of 0.1–0.2 nm. The Al films are superconducting with critical temperatures ranging from 1.23 to around 2 K, depending on the film thickness. [ABSTRACT FROM AUTHOR]

Zhaoyong Li,1,&ast; Yanping Lin,1,&ast; Ting Qiu,2,&ast; Junsheng Liang,1 Yintao Lan,3 Fan Meng,4 Chaohao Liang,4 Yiqing Zhang,4 Qingyun Wang,1 Da Shi,1 Changli Zhang,1 Yanan Shi,1 Liujun Liu,1 Yanlan Yang,1 Jian Zhang4,5 1Department of Radiology, DongGuan Tungwah Hospital, Dongguan Key Laboratory of Radiology and Molecular Imaging, DongGuan, Guangdong, 523000, People’s Republic of China; 2Department of Radiology, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, 519000, People’s Republic of China; 3Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, Guangdong, 510030, People’s Republic of China; 4School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China; 5Department of Oncology, the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, Guangdong, 511500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Zhang; Zhaoyong Li, Email jianzhang@gzhmu.edu.cn; lizhaoyong2003@163.comBackground: Photothermal therapy (PTT) guided by photoacoustic imaging (PAI) using nanoplatforms has emerged as a promising strategy for cancer treatment due to its efficiency and accuracy. This study aimed to develop and synthesize novel second near-infrared region (NIR-II) absorption-conjugated polymer acceptor acrylate-substituted thiadiazoloquinoxaline-diketopyrrolopyrrole polymers (PATQ-DPP) designed specifically as photothermal and imaging contrast agents for nasopharyngeal carcinoma (NPC).Methods: The PATQ-DPP nanoparticles were synthesized and characterized for their optical properties, including low optical band gaps. Their potential as PTT agents and imaging contrast agents for NPC was evaluated both in vitro and in vivo. The accumulation of nanoparticles at tumor sites was assessed post-injection, and the efficacy of PTT under near-infrared laser irradiation was investigated in a mouse model of NPC.Results: Experimental results indicated that the PATQ-DPP nanoparticles exhibited significant photoacoustic contrast enhancement and favorable PTT performance. Safety and non-toxicity evaluations confirmed the biocompatibility of these nanoparticles. In vivo studies showed that PATQ-DPP nanoparticles effectively accumulated at NPC tumor sites and demonstrated excellent tumor growth inhibition upon exposure to near-infrared laser irradiation. Notably, complete elimination of nasopharyngeal tumors was observed within 18 days following PTT.Discussion: The findings suggest that PATQ-DPP nanoparticles are a promising theranostic agent for NIR-II PAI and PTT of tumors. This innovative approach utilizing PATQ-DPP nanoparticles provides a powerful tool for the early diagnosis and precise treatment of NPC, offering a new avenue in the management of this challenging malignancy.Keywords: nasopharyngeal carcinoma, photoacoustic imaging, photothermal therapy, PATQ-DPP nanoparticles

Jiaqiong Lin,1,2 Yan Lin,3 Xiaoyong Li,4 Fei He,5 Qinyuan Gao,3 Yuanjun Wang,3 Zena Huang,3 Fu Xiong5,6 1Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, People’s Republic of China; 2Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan, People’s Republic of China; 3Yunkang School of Medicine and Health, Nanfang College, Guangzhou, People’s Republic of China; 4General Surgery Department; Guangdong Provincial Key Laboratory of Major Obstetric Diseases; Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology; The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 5Department of Medical Genetics/Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 6Department of Fetal Medicine and Prenatal Diagnosis, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Fu Xiong, Department of Medical Genetics/Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People’s Republic of China, Email xiongfu@smu.edu.cn Zena Huang, Yunkang School of Medicine and Health, Nanfang College, Guangzhou, 510970, People’s Republic of China, Email 506647168@qq.comBackground: Diabetic kidney disease (DKD) is an intricate complication of diabetes with limited treatment options. Anoikis, a programmed cell death activated by loss of cell anchorage to the extracellular matrix, participated in various physiological and pathological processes. Our study aimed to elucidate the role of anoikis-related genes in DKD pathogenesis.Methods: Differentially expressed genes (DEGs) associated with anoikis in DKD were identified. Weighted gene co-expression network analysis (WGCNA) was conducted to identify DKD-correlated modules and assess their functional implications. A diagnostic model for DKD was developed using LASSO regression and Gene set variation analysis (GSVA) was performed for enrichment analysis. Experimental validation was employed to validate the significance of selected genes in the progression of DKD.Results: We identified 10 anoikis-related DEGs involved in key signaling pathways impacting DKD progression. WGCNA highlighted the yellow module’s significant enrichment in immune response and regulatory pathways. Correlation analysis further revealed the association between immune infiltration and anoikis-related DEGs. Our LASSO regression-based diagnostic model demonstrated a well-predictive efficacy with seven identified genes. GSVA indicated that gene function in the high-risk group was primarily associated with immune regulation. Further experimental validation using diabetic mouse models and data analysis in the single-cell dataset confirmed the significance of PYCARD and SFN in DKD progression. High glucose stimulation in RAW264.7 and TCMK-1 cells showed significantly increased expression levels of both Pycard and Sfn. Co-expression analysis demonstrated distinct functions of PYCARD and SFN, with KEGG pathway analysis showing significant enrichment in immune regulation and cell proliferation pathway.Conclusion: In conclusion, our study provides valuable insights into the molecular mechanisms involved in DKD pathogenesis, specifically highlighting the role of anoikis-related genes in modulating immune infiltration. These findings suggest that targeting these genes may hold promise for future diagnostic and therapeutic approaches in DKD management.Keywords: diabetic kidney disease, anoikis, immune infiltration, biomarker, PYCARD, SFN

Yunpeng Cui,1 Qiwei Wang,1 Chuan Mi,1 Bing Wang,1 Yuanxing Pan,1 Yunfei Lin,1 Rui He,2 Liying Sun,3 Bo Zheng,4 Xuedong Shi1 1Department of Orthopaedics, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Plastic Surgery and Burn, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, Peking University First Hospital, Beijing, People’s Republic of China; 4Department of Clinical Pharmacology, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xuedong Shi, Department of Orthopedic, Peking University First Hospital, Beijing, People’s Republic of China, Email pku_ortho@163.comBackground: This retrospective cohort study explores a practical approach to acquiring pathogenic microorganisms in patients with bone and joint infections.Methods: From Aug 2018 to Mar 2022, 68 consecutive patients (87 cultures) with bone and joint infection were recruited in this study. All cultures followed the Peking University First Hospital Procedure of Culturing Pathogenic microorganisms for bone and joint infection. Tissue samples were obtained through fluoroscopy-guided biopsy or open debridement. Tissue samples were divided into manual homogenization (MH), manual mixture (MM), and pathological examination. The baseline, antibiotic exposure, laboratory, surgical, and microbial data were reviewed. Independent sample T-test, Mann–Whitney U-test, and Chi-square test were used to detect the difference between patients who received different processing measures.Results: The average age was 55.8± 2.4 years old. Thirty-nine patients were male. The total positive culture rate of the manual homogenization group was 80.5% (70/87). Thirty-five patients had mixed infections with more than one microorganism cultured. Staphylococci accounted for 60.23% of all microorganisms. Staphylococcus aureus (18.2%) and Staphylococcus epidermidis (15.9%) were the two most common bacteria cultured in this study. Patients with positive culture in the manual mixture group had significantly higher WBC (p = 0.006), NE% (p = 0.024), ESR (p = 0.003), CRP (p = 0.020) and IL6 (0.050) compared to patients with negative culture. After tissue homogenization, only ESR is still statistically different. Patients without SIRS had a low positive culture rate (59.4%). Tissue homogenization could significantly increase the positive culture rate of patients without SIRS. Pre-culture antibiotic exposure was not an independent risk factor for culture results.Conclusion: Peking University First Hospital Procedure for Culturing Pathogenic microorganisms for Bone and Joint Infections was a practical approach for obtaining pathogenic microorganisms.Keywords: bone and joint infection, systemic inflammatory response syndrome, antibiotic, tissue homogenization

Xian-Ping Yang,1,&ast; Ying-Yao Liu,2,&ast; Cai-Yun Zhang,3 Kai-Kai Huang,1 Shan-Shan Han,1 Bao-Ying Liang,1 Ying Lin1 1Department of Dermatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong, People’s Republic of China; 2The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Department of Dermatology, Dongguan Traditional Chinese Medicine Hospital, Dongguan, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Lin, Department of Dermatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), No. 111 Dade Road, Guangzhou, Guangdong, 510120, People’s Republic of China, Email lin19791226@gzucm.edu.cnAim: Atopic dermatitis (AD) often accompanies skin infections, and bacterial skin infections often cause persistent and worsening symptoms. In this study, we explored the key changes in the microbiota of AD patients, as well as the effects of different ages and the severity of rash on changes in the microbiota.Patients and Methods: A total of 95 AD patients and 77 healthy volunteers were recruited. The AD patients were divided into three groups based age and three groups according to the EASI score. Microorganisms collected from the skin were analyzed through 16S rRNA gene sequencing, revealing species diversity via α and β diversity analyses. Species compositions were compared at the phylum and genus levels. The significance of skin microbiota at the genus level was assessed using the random forest algorithm. Finally, the impact of relationships between different microbial communities on the microbial community composition and the pathogenesis of AD was explored using Pearson correlation coefficients.Results: The species diversity of the skin microbiota in the AD group significantly decreased. Compared with that in the healthy volunteers (HV) group, the bacterial diversity in the two groups of samples significantly differed. Staphylococcus dominated the bacterial communities, and as AD symptoms gradually worsened, the abundance of Staphylococcus gradually increased. Among all bacterial genera with a relative abundance greater than 1%, Staphylococcus showed a negative correlation with other genera, and showed significant consistency in specimens from different age groups.Conclusion: Changes in the abundance of Staphylococcus in the skin bacterial colonies are the main cause of AD. Brevundimonas, Paracoccus, Corynebacterium, and Veillonella may serve as characteristic biomarkers for AD. These results indicate that altering the microbiota composition of the skin may aid in the treatment of AD.Keywords: atopic dermatitis, skin bacterial colony, 16S rRNA gene sequencing

The great hammerhead shark Sphyrna mokarran and the scalloped hammerhead shark S. lewini are marine top predators with global distributions. However, limited information is available on the trophic ecology of hammerhead sharks in the Indian Ocean. In this study, we measured stable nitrogen and carbon isotopes in the muscle tissues of neonates and juveniles of S. mokarran and S. lewini from the waters of the western Arabian Gulf. In general, values of δ15N were lower in S. mokarran (10.8-18.7‰) than in S. lewini (12.2-18.7‰), indicating a reliance on food sources with low nitrogen values. Isotopic niche similarities were observed between female and male S. mokarran. We further observed considerable ontogenetic changes in the δ15N values of both S. mokarran and S. lewini neonates (a reduction from 19 to 12‰), reflecting the maternal effect. The effects of total length and sex on the nitrogen and stable isotope values were nonsignificant in S. mokarran juveniles. The western Arabian Gulf likely serves as a key feeding ground for both the neonates and the juveniles of S. mokarran. By contrast, S. lewini appears to have a low level of reliance on this region.

Qiao Zhang,1,&ast; Lei Shi,1,&ast; Yanping Lin,2,&ast; Huirong Dai,1 Yixuan Bai,1 Pan You1 1Xiamen Xianyue Hospital, Xianyue Hospital Affiliated to Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, Fujian, 361012, People’s Republic of China; 2The Third Hospital of Xiamen, Xiamen, Fujian, 361100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pan You, Xiamen Xianyue Hospital, Xianyue Hospital Affiliated to Xiamen Medical College, Fujian Psychiatric Center, Fujian Clinical Research Center for Mental Disorders, Xiamen, Fujian, 361012, People’s Republic of China, Tel/Fax +86-592-5392620, Email panyou001@yahoo.comPurpose: In this study, we investigated the differences in clinical biochemical values and mitochondrial mass between schizophrenia patients with and without COVID-19, so as to provide assistance to the treatment and management of COVID-19 positive patients with schizophrenia.Patients and methods: We undertook an exploratory, retrospective review of patient data from Dec. 6, 2022, to Jan. 31, 2023. A total of 1696 inpatients with psychosis (921 schizophrenia patients and 775 diagnosed with other mental diseases) during this period were identified. Finally, 60 schizophrenia patients were enrolled in our study, and 20 of them were infected with syndrome coronavirus 2 (SARS-CoV-2). The serum biochemical levels and single-cell mitochondrial mass (SCMM) of the T lymphocytes of all schizophrenia patients were analyzed.Results: The serum levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatinine (Cr) and lactate dehydrogenase (LDH) were significantly higher in schizophrenia patients with COVID-19 (SCZ-C) group. In addition, the SCZ-C group showed lower CD3+, CD3+CD4+ and CD3+CD8+ cell counts and higher SCMM of T lymphocytes compared to SCZ group. Furthermore, positive correlations were found between the T-cell subpopulation counts and positive symptom scores on the Positive and Negative Syndrome Scale (PANSS).Conclusion: Our study findings showed that schizophrenia patients with COVID-19 have a phenotype of mitochondrial damage in T lymphocytes and higher serum levels of AST, ALP, Cr and LDH, which might provide evidence for treating individuals with schizophrenia during subsequent spread of infectious disease.Keywords: biochemical characteristics, lymphocyte, mitochondrial damage, COVID-19, schizophrenia

Abstract Adverse neonatal outcomes are a prevailing risk factor for both short- and long-term mortality and morbidity in infants. Given the importance of these outcomes, refining their assessment is paramount for improving prevention and care. Here we aim to enhance the assessment of these often correlated and multifaceted neonatal outcomes. To achieve this, we employ factor analysis to identify common and unique effects and further confirm these effects using criterion-related validity testing. This validation leverages methylome-wide profiles from neonatal blood. Specifically, we investigate nine neonatal health risk variables, including gestational age, Apgar score, three indicators of body size, jaundice, birth diagnosis, maternal preeclampsia, and maternal age. The methylomic profiles used for this research capture data from nearly all 28 million methylation sites in human blood, derived from the blood spot collected from 333 neonates, within 72 h post-birth. Our factor analysis revealed two common factors, size factor, that captured the shared effects of weight, head size, height, and gestational age and disease factor capturing the orthogonal shared effects of gestational age, combined with jaundice and birth diagnosis. To minimize false positives in the validation studies, validation was limited to variables with significant cumulative association as estimated through an in-sample replication procedure. This screening resulted in that the two common factors and the unique effects for gestational age, jaundice and Apgar were further investigated with full-scale cell-type specific methylome-wide association analyses. Highly significant, cell-type specific, associations were detected for both common effect factors and for Apgar. Gene Ontology analyses revealed multiple significant biologically relevant terms for the five fully investigated neonatal health risk variables. Given the established links between adverse neonatal outcomes and both immediate and long-term health, the distinct factor effects (representing the common and unique effects of the risk variables) and their biological profiles confirmed in our work, suggest their potential role as clinical biomarkers for assessing health risks and enhancing personalized care.

Yongxu Lin,1,2 Yaling Liu,3 Qiuyan Lin,1,2 Mingrong Wang,1,2 Pingying Jiang,1,2 Kaiyi Mao,1,2 Fenglin Chen,1,2 Jian Ding,3 Dan Li1,2 1Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 2Fujian Clinical Research Center for Digestive System Tumors and Upper Gastrointestinal Diseases, Fuzhou, People’s Republic of China; 3Department of Gastroenterology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, People’s Republic of ChinaCorrespondence: Dan Li, No. 29 Xinquan Road, Fuzhou, 350001, People’s Republic of China, Email doctorlidan99@fjmu.edu.cn Jian Ding, No. 20 Chazhong Road, Fuzhou, 350005, People’s Republic of China, Email docdingjian@163.comPurpose: Early detection of hyperlipidemic acute pancreatitis (HLAP) with exacerbation tendency is crucial for clinical decision-making and improving prognosis. The aim of this study was to establish a reliable model for the early prediction of HLAP severity.Patients and Methods: A total of 225 patients with first-episode HLAP who were admitted to Fujian Medical University Union Hospital from June 2012 to June 2023 were included. Patients were divided into mild acute pancreatitis (MAP) or moderate-severe acute pancreatitis and severe acute pancreatitis (MSAP+SAP) groups. Independent predictors for progression to MSAP or SAP were identified through univariate analysis and least absolute shrinkage and selection operator regression. A nomogram was established through multivariate logistic regression analysis to predict this progression. The calibration, receiver operating characteristic(ROC), and clinical decision curves were employed to evaluate the model’s consistency, differentiation, and clinical applicability. Clinical data of 93 patients with first-episode HLAP who were admitted to the First Affiliated Hospital of Fujian Medical University from October 2015 to October 2022 were collected for external validation.Results: White blood cell count, lactate dehydrogenase, albumin, serum creatinine, serum calcium, D-Dimer were identified as independent predictors for progression to MSAP or SAP in patients with HLAP and used to establish a predictive nomogram. The internally verified Harrell consistency index (C-index) was 0.908 (95% CI 0.867– 0.948) and the externally verified C-index was 0.950 (95% CI 0.910– 0.990). The calibration, ROC, and clinical decision curves showed this nomogram’s good predictive ability.Conclusion: We have established a nomogram that can help identify HLAP patients who are likely to develop MSAP or SAP at an early stage, with high discrimination and accuracy.Keywords: early prediction, nomogram, hyperlipidemic acute pancreatitis, risk factor, prognosis

Guixing Zeng,1 Yujie Lin,2 Peirui Xie,3 Jiarong Lin,4 Yaxing He,5 Junping Wei1 1Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3The First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, People’s Republic of China; 5School of Instrumentation and Optoelectronic Engineering, Beihang University, Beijing, People’s Republic of ChinaCorrespondence: Junping Wei, Email weijunping@126.comBackground: To investigate the association between the NLR and the risk of all-cause and cardiovascular mortality in US adults with diabetic kidney disease (DKD).Methods: The data utilized for this analysis were sourced from ten National Health and Nutrition Examination Survey cycles (1999– 2018) with mortality data (up to 31 December 2019) via linkage to the National Death Index. The optimum NLR threshold for predicting survival outcomes was determined through the maximally selected rank statistics. Restricted cubic spline (RCS), weighted Cox proportional hazard regression, stratified analyses, and time-dependent receiver-operating characteristic curve (ROC) were employed to delineate the prospective correlations of the NLR with both all-cause and cardiovascular mortality.Results: In this investigation, a cohort comprising 2581 patients diagnosed with DKD was examined, encompassing 624 individuals with a higher NLR (≥ 3.07) and 1957 subjects with a lower NLR (< 3.07). Over a median follow-up of 79 months (interquartile range, 44– 128 months), 1103 deaths occurred, including 397 from cardiovascular causes and 706 from non-cardiovascular causes. The RCS analysis elucidated the positive linear correlation (both nonlinear P > 0.05). In the multivariable analyses, each one-unit increase in the NLR value was correlated with a 51% increased risk of all-cause mortality (1.51(1.28, 1.77)) and a 71% increased risk of cardiovascular mortality (1.71(1.32, 2.21)). The results were largely consistent across stratified analyses encompassing variables such as age, sex, race/ethnicity, marital status, family income, education levels, BMI, drinking status, smoking status, hypertension, CVD, and anti-infective drugs (P for interaction > 0.05 for all). Time-dependent ROC analyses underscored the NLR’s credible predictive efficacy for both short-term and extended durations in forecasting both all-cause and cardiovascular mortality.Conclusion: The findings emphasize the promising use of the NLR in stratifying and prognosticating the risk of mortality in DKD in clinical practice.Keywords: neutrophil–lymphocyte ratio, diabetic kidney disease, predictor, mortality, cohort study

Shaohua Tan,1,&ast; Xiangchen Li,2,&ast; Bing Lu,1,3 Yibin Lin,3 Yunxiang Cai,1 Jie He,4 Sisi Chen,2 Junli Gao,2 Junshun Gao,2 Xinhua Qiang1 1Department of Clinical Laboratory, The First People’s Hospital of Huzhou, Huzhou, Zhejiang, 313000, People’s Republic of China; 2Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, 310020, People’s Republic of China; 3School of Medicine, Huzhou University, Huzhou, Zhejiang, 313000, People’s Republic of China; 4Department of Infectious Diseases, The First People’s Hospital of Huzhou, Huzhou, Zhejiang, 313000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinhua Qiang, Department of Clinical Laboratory, The First People’s Hospital of Huzhou, No. 158 Back Square Road, Wuxing District, Huzhou, Zhejiang, 313000, People’s Republic of China, Email qiangxinhua@zjhu.edu.cnAbstract: Carbapenem-resistant Salmonella enterica (S. enterica) pose a significant threat to public health, causing gastroenteritis and invasive infections. We report the first emergence of a carbapenem-resistant S. enterica serovar London strain, A132, carrying the blaNDM-5 gene in China. Whole-genome sequencing and bioinformatics analysis assigned A132 to be ST155, a multidrug-resistant clone frequently reported in China. The strain A132 exhibited resistance to multiple antibiotics, with 20 acquired antibiotic resistance genes (ARGs) identified, predominantly located on the IncFIB plasmid (pA132-1-NDM). Notably, the blaNDM-5 gene was located within an IS 26 flanked-class 1 integron-ISCR1 complex, comprising two genetic cassettes. One cassette is the class 1 integron, which may facilitate the transmission of the entire complex, while the other is the blaNDM-5-containing ISCR1-IS 26-flanked cassette, carrying multiple other ARGs. Genbank database search based on the blaNDM-5-carrying cassette identified a similar genetic context found in transmissible IncFIA plasmids from Escherichia coli (p91) and Enterobacter hormaechei (p388) with a shared host range, suggesting the potential for cross-species transmission of blaNDM-5. To our knowledge, this is the first reported case of Salmonella serovar London ST155 harboring blaNDM-5 gene. Phylogenetic analysis indicated a close relationship between A132 and eight S. London ST155 strains isolated from the same province. However, A132 differed by carrying the blaNDM-5 gene and four unique ARGs. Given the high transmissibility of the F-type plasmid harboring blaNDM-5 and 18 other ARGs, it is imperative to implement vigilant surveillance and adopt appropriate infection control measures to mitigate the threat to public health.Keywords: blaNDM-5, Salmonella London, ST155, carbapenem resistance, IncFIB, integron