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Tinghua Hu,1,&ast; Shanshan Dai,2,&ast; Lan Yang,1 Bo Zhu1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710000, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Xi’an No. 9 Hospital, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Zhu, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xi’an, Shaanxi, 710061, People’s Republic of China, Email zhubo685689@163.comBackground: COPD, combined with Osteoporosis, has a high incidence and potential for great harm. Choosing an optimal diagnostic method to achieve bone mineral density (BMD) screening is crucial for COPD patients. Studies on COPD patients with BMD reduction are lacking.Purpose: To identify the risk factors of BMD reduction and osteoporosis in COPD patients.Patients and Methods: We included a total of 81 patients with AECOPD, who were admitted to the hospital from July 1, 2019, to January 31, 2020. Patients were grouped into BMD normal group, BMD reduced group and OP group. The areas under ROC curve were used to explore the value of CT values in the diagnosis of bone abnormality, and clinical indicators were collected.Results: The CT value of the vertebral cancellous bone is highly correlated with the T value of BMD (R > 5.5, P < 0.0001). Using multivariate Logistic regression analysis, we showed that COPD duration, BMI, 25-hydroxyvitamin D3, and long-term inhaled glucocorticoid were independent factors affecting different BMD levels in COPD patients. No significant difference in bone formation indexes between groups. β-crossL was negatively correlated with serum IL-6 (r=− 0.254, P=0.022), and ALP was positively correlated with serum TNF-α (r=0.284, P=0.023).Conclusion: Thoracolumbar vertebral cancellous bone CT has potential value in the diagnosis of bone abnormality. COPD duration, BMI, 25-hydroxyvitamin D3, and long-term inhaled glucocorticoid may contribute to the BMD reduction in COPD patients, and serum IL-6 and TNF-α regulate bone metabolism in COPD patients.Keywords: chronic obstructive pulmonary disease, osteoporosis, bone mineral density, chest CT

Weijian Liu,&ast; Liangzi Yang,&ast; Hongjuan Qin, Peize Zhang Department of Pulmonary Medicine and Tuberculosis, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peize Zhang, Email 82880246@qq.comAbstract: Tuberculosis(TB) is a serious infection that affects transplant recipients, particularly in high TB burden countries. Clinical presentation of these patients is atypical, and the care and management are frequently tricky as multi-drug interaction and intolerable adverse effects. Contezolid, a novel oxazolidinone antibacterial agent, had been demonstrated to be effective for TB in vitro and had been shown in some clinical cases with a more favorable safety profile than linezolid, the first-generation oxazolidinone, which had a commonly seen myelosuppression and neuropathy. Additionally, Contezolid has a unique metabolic mechanism that leads to less drug interaction. Here, we report a case of multi-system TB in a transplant recipient with chronic kidney allograft dysfunction. She was intolerant to most first and second-line anti-TB drugs and repeatedly developed ascites and nocturnal low-grade fever. She finally achieved good efficacy and safety results after enhanced anti-TB treatment with the addition of contezolid. Given the increased risk of TB in patients with organ transplantation and multi-drug interaction in patients with severe comorbidities, further clinical studies are needed to investigate the application and appropriate dosage of contezolid in patients with active TB.Keywords: tuberculosis, contezolid, kidney dysfunction, kidney transplantation, tuberculous peritonitis

Liu Yang,1 Yan Xu,1 Jian Pan,2– 4 Renjie Li,1 Chao Lan,1 Dongshan Zhang2– 4 1Department of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Emergency Medicine and Difficult Diseases Institute, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Chao Lan, Department of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, People’s Republic of China, Tel +86 13663855629, Email fcclanc@zzu.edu.cn Dongshan Zhang, Department of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Tel +86 138 7589 9625, Email dongshanzhang@csu.edu.cnBackground: Acute kidney injury (AKI) is associated with higher perioperative mortality and morbidity, as well as increased medical expenses. The molecular mechanisms underlying ischemia-reperfusion (I/R)-induced AKI remain unclear.Methods and Results: We applied an RT-qPCR assay to measure the expression of mmu-lncRNA129814, hsa-lncRNA582795, and miRNA-494-5p, immunoblotting to detect IL-1α and cleaved caspase-3 expression, and TUNEL staining and flow cytometry (FCM) to evaluate apoptosis. The experiments were conducted using BUMPT and HK-2 cells, as well as C57BL/6J mice. Mechanistically, mmu-lncRNA129814 could sponge miRNA-494-5p and upregulate IL-1α expression to promote cell apoptosis. Furthermore, knockdown of mmu-lncRNA129814 ameliorated I/R-induced progression of AKI by targeting the miRNA-494-5p/IL-1α pathways. Interestingly, hsa-lncRNA582795, a homolog of mmu-lncRNA129814, also promoted I/R-stimulated HK-2 cell apoptosis and AKI progression by regulating the miRNA-494-5p/IL-1α axis. Finally, we found that patients with I/R-induced AKI exhibited significantly elevated plasma and urinary levels of hsa-lncRNA582795 compared to those who underwent ischemia-reperfusion without developing AKI. Spearman’s test demonstrated a significant correlation between serum creatinine and plasma hsa-lncRNA582795 in I/R patients. Plasma hsa-lncRNA582795 showed high sensitivity but low specificity (86.7%) compared to urinary hsa-lncRNA582795.Conclusion: The mmu-lncRNA129814/hsa-lncRNA582795/miRNA-494-5p/IL-1α axis was found to modulate the progression of ischemic AKI, and hsa-lncRNA582795 could act as a diagnosis biomarker and potential therapy target of I/R-induced AKI. Keywords: AKI, mmu-lncRNA129814, hsa-lncRNA582795, apoptosis, biomarker

Min Wang,1,&ast; Lin Yang,1,&ast; Suhan Zhang,2 Meng Wu,1 Zhenfeng Sun,3 Liu Shen,1 Xiaowei Xu,1 Liangkun Ma,2 Jiao Li1 1Institute of Medical Information/Library, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100020, People’s Republic of China; 2Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 3Daxing District Maternal and Child Health Hospital, Beijing, 102699, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiao Li, Institute of Medical Information & Library Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100020, People’s Republic of China, Tel +8618618461596, Email li.jiao@imicams.ac.cnBackground: Maternity health management has always been the area of concern and considering, and considering its complexity and multidisciplinary, it is necessary to provide effective training for healthcare workers.Purpose: To evaluate the impact of a multidisciplinary experiential training model on the knowledge, attitude, and practice of healthcare workers in maternity health management.Patients and Methods: We conducted a novel educational model, Multidisciplinary Maternity Health Experiential Training based on Knowledge, Attitude and Practice (MMHET), which combined theoretical knowledge, practical skills, and human-centred humanistic care, offering a comprehensive offline education program supported by online teaching materials structured around knowledge graphs. Pre- and post-test surveys were used to assess the changes in participants’ knowledge, attitudes, and practices.Results: From May to July 2023, a total of 322 participants attended the course, and only a small percentage had participated in experiential training. For all topics, the vast majority of participants endorsed the course, and the attitude content had the highest percentage of participants who said they agreed. Among the groups with different years of working life, the highest percentage of participants in the > 20 years group strongly endorsed the course.Conclusion: The preliminary findings indicate that the MMHET model is well-received and feasible, demonstrating its potential to enhance maternity health management education.Keywords: continuing education, pregnancy health, assessment, healthcare, medical education

Zhou Zhu,1– 3,&ast; Huizi Gong,4,&ast; Mingjuan Liu,1– 3 Hanlin Zhang,1,2 Leyan Yang,1,2 Xinyi Zhang,5 Heyi Zheng,1,2 Yanfeng Li,6 Mingli Li,7 Jun Li1,2 1Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3 4+4 Medical Doctor Program, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Dermatology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Departments of Internal Medicine and Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT, USA; 6Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 7Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingli Li, Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Email limingli@pumch.cn Jun Li, Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Email lijun35@hotmail.comBackground: Tabes dorsalis is a late manifestation of neurosyphilis, characterized by progressive ataxia, lightning pains, loss of proprioception, and urinary incontinence. The absence of a definitive diagnostic standard and the non-specific clinical manifestations have led to a significant rate of misdiagnoses.Methods: Hospitalized patients with tabes dorsalis at Peking Union Medical College Hospital between January 2010 and December 2023 were reviewed.Results: A total of 13 patients were included, with 10 males and 3 females. The median age was 50 years (range, 34– 64). The most frequent initial symptoms were limb numbness (30.8%) and lightning pains (30.8%). Eleven patients (84.6%) received misdiagnoses prior to the final diagnosis. The most frequently observed physical sign was positive Romberg’s sign (84.6%). Notably, Argyll Robertson pupil was presented in 7 subjects (53.8%). Serological tests revealed positive rapid plasma regain (RPR) and Treponema pallidum particle agglutination (TPPA) for all patients. All CSF samples were TPPA-reactive. Intramedullary hyperintensity on T2-weighted imaging of spinal MRI was found in 5 patients (38.5%). All patients received anti-syphilitic treatment, with effective treatment recorded in five cases.Conclusion: This study underscores the importance of neurological symptoms and signs in diagnosing tabes dorsalis. Individuals with progressive ataxia and positive Romberg’s sign should be closely monitored for potential neurosyphilis. Integrating clinical features, laboratory tests, and neuroimaging could reduce misdiagnosis and expedite the initiation of anti-syphilitic therapy.Keywords: tabes dorsalis, neurosyphilis, ataxia, cerebrospinal fluid

Luxun Yang,1,&ast; Haiying Ran,2,&ast; Yaru Yin,1 Jing Liu,1 Binghui Lu,1 Xi Ran,3 Shenglin Luo,1 Weidong Wang,4 Zhangyou Yang,5 Rong Li1 1Institute of Combined Injury, National Key Laboratory of Trauma and Chemical Poisoning, Army Key Laboratory of Nanomedicine, Department of Military Preventive Medicine, Army Medical University, Chongqing, 400038, People’s Republic of China; 2Biomedical Analysis Center, Army Medical University, Chongqing, 400038, People’s Republic of China; 3Department of Medical Laboratory, Xinqiao Hospital, Army Medical University, Chongqing, 400037, People’s Republic of China; 4Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu, 610041, People’s Republic of China; 5Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing Pharmacodynamic Evaluation Engineering Technology Research Center, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhangyou Yang, Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing, 400016, People’s Republic of China, Email yangzhangyou@cqmu.edu.cn Rong Li, Army Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, People’s Republic of China, Tel +86-13883996627, Fax +8623-68753127, Email lrong361@126.comPurpose: Mitochondrial oxidative stress is an important factor in cell apoptosis. Cerium oxide nanomaterials show great potential for scavenging free radicals and simulating superoxide dismutase (SOD) and catalase (CAT) activities. To solve the problem of poor targeting of cerium oxide nanomaterials, we designed albumin-cerium oxide nanoclusters (TPP-PCNLs) that target the modification of mitochondria with triphenyl phosphate (TPP). TPP-PCNLs are expected to simulate the activity of superoxide dismutase, continuously remove reactive oxygen species, and play a lasting role in radiation protection.Methods: First, cerium dioxide nanoclusters (CNLs), polyethylene glycol cerium dioxide nanoclusters (PCNLs), and TPP-PCNLs were characterized in terms of their morphology and size, ultraviolet spectrum, dispersion stability and cellular uptake, and colocalization Subsequently, the anti-radiation effects of TPP-PCNLs were investigated using in vitro and in vivo experiments including cell viability, apoptosis, comet assays, histopathology, and dose reduction factor (DRF).Results: TPP-PCNLs exhibited good stability and biocompatibility. In vitro experiments indicated that TPP-PCNLs could not only target mitochondria excellently but also regulate reactive oxygen species (ROS)levels in whole cells. More importantly, TPP-PCNLs improved the integrity and functionality of mitochondria in irradiated L-02 cells, thereby indirectly eliminating the continuous damage to nuclear DNA caused by mitochondrial oxidative stress. TPP-PCNLs are mainly targeted to the liver, spleen, and other extramedullary hematopoietic organs with a radiation dose reduction factor of 1.30. In vivo experiments showed that TPP-PCNLs effectively improved the survival rate, weight change, hematopoietic function of irradiated animals. Western blot experiments have confirmed that TPP-PCNLs play a role in radiation protection by regulating the mitochondrial apoptotic pathway.Conclusion: TPP-PCNLs play a radiologically protective role by targeting extramedullary hematopoietic organ-liver cells and mitochondria to continuously clear ROS.Keywords: radioprotective effect, ceria nanoclusters, mitochondria targeting, oxidative stress, superoxide dismutase

Dazhen Wang,1,&ast; Zhengfeng Zhang,2,&ast; Liu Yang,1 Lu Zhao,1 Ze Liu,1 ChangJie Lou1 1Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Department of Hematopathology, The Second Clinical Medical College, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: ChangJie Lou, Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150081, People’s Republic of China, Email 601245@hrbmu.edu.cnPurpose: Comparing the efficacy and safety of programmed cell death protein-1 (PD-1) inhibitors combined with tyrosine kinase inhibitors (TKIs) with or without hepatic artery infusion chemotherapy (HAIC) in HBV-related advanced HCC and exploring prognostic predictors of the combined regimen.Patients and Methods: A total of 194 patients diagnosed with HBV-related advanced HCC between 2020 and 2022 were included in the study, including 99 in the HAIC combined with PD-1 inhibitors plus TKIs (HPT group) and 95 in the PD-1 inhibitors plus TKIs (PT group). The efficacy was evaluated according to the tumor response rate and survival, and the safety was evaluated according to the adverse events.Results: The HPT group showed higher overall response rate and disease control rate than the PT group. The median overall survival (OS) of the HPT group and the PT group were 18.10 months and 12.57 months, respectively, and the difference was statistically significant (hazard ratio (HR) = 0.519, 95% confidence interval (CI): 0.374– 0.722, P

Lin Tang,1,&ast; Jian Liu,2,&ast; Hui Yang,2,&ast; Hong-Qing Zhao,3 Chao Hu,4 Si-Jing Ma,5 Yu-Hui Qing,6 Lei Yang,1 Rong-Rong Zhou,5 Shui-Han Zhang6 1Hospital-Made Preparations Center, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 2Medical Innovation Experiment Center, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 3Science & Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 4Department of Pharmacy, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 5The Affiliated Hospital, Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 6Institute of Chinese Medicine Resources, Hunan Academy of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rong-Rong Zhou; Shui-Han Zhang, Tel +86-0731-85920129, Email rrzhou0823@163.com; zhangshuihan0220@126.comPurpose: The Baihe Dihuang decoction (BDD) is a representative traditional Chinese medicinal formula that has been used to treat anxiety disorders for thousands of years. This study aimed to reveal mechanisms of anxiolytic effects of BDD with multidimensional omics.Methods: First, 28-day chronic restraint stress (CRS) was used to create a rat model of anxiety, and the open field test and elevated plus maze were used to assess anxiety-like behavior. Enzyme-linked immunosorbent assay (ELISA), hematoxylin–eosin staining, and immunofluorescence staining were used to evaluate inflammatory response. Besides, 16S rRNA gene sequencing assessed fecal microbiota composition and differential microbiota. Non-targeted metabolomics analysis of feces was performed to determine fecal biomarkers, and targeted metabolomics was used to observe the levels of hippocampus neurotransmitters. Finally, Pearson correlation analysis was used to examine relationships among gut microbiota, fecal metabolites, and neurotransmitters.Results: BDD significantly improved anxiety-like behaviors in CRS-induced rats and effectively ameliorated hippocampal neuronal damage and abnormal activation of hippocampal microglia. It also had a profound effect on the diversity of microbiota, as evidenced by significant changes in the abundance of 10 potential microbial biomarkers at the genus level. Additionally, BDD led to significant alterations in 18 fecal metabolites and 12 hippocampal neurotransmitters, with the majority of the metabolites implicated in amino acid metabolism pathways such as D-glutamine and D-glutamate, alanine, arginine and proline, and tryptophan metabolism. Furthermore, Pearson analysis showed a strong link among gut microbiota, metabolites, and neurotransmitters during anxiety and BDD treatment.Conclusion: BDD can effectively improve anxiety-like behaviors by regulating the gut–brain axis, including gut microbiota and metabolite modification, suppression of hippocampal neuronal inflammation, and regulation of neurotransmitters. Keywords: Baihe Dihuang decoction, 16S rRNA, metabolomics, anxiety, neurotransmitter

Yiyue Xu,1,&ast; Haoqian Li,1,&ast; Xiaoqing Wang,2 Butuo Li,1 Aiqin Gao,1 Qian Zhao,1 Linlin Yang,1 Wenru Qin,1 Linlin Wang1 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 2Department of Portal Hypertension, Shandong Public Health Clinical Center, Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linlin Wang, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 JiYan Road, Jinan, 250117, People’s Republic of China, Tel +86-13793187739, Email wanglinlinatjn@163.comBackground: COVID-19 has spread worldwide, becoming a global threat to public health and can lead to complications, especially pneumonia, which can be life-threatening. However, in lung cancer patients, the prediction of pneumonia and severe pneumonia has not been studied. We aimed to develop effective models to assess pneumonia after SARS-CoV-2 infection in lung cancer patients to guide COVID-19 management.Methods: We retrospectively recruited 621 lung cancer patients diagnosed with COVID-19 via SARS-CoV-2 RT-PCR analysis in two medical centers and divided into training and validation group, respectively. Univariate and multivariate logistic regression analysis were used to identify independent risk factors of all-grade pneumonia and ≥ grade 2 pneumonia in the training group. Nomograms were established based on independent predictors and verified in the validation group. C-index, ROC curves, calibration curve, and DCA were used to evaluate the nomograms. Subgroup analyses in immunotherapy or thoracic radiotherapy patients were then conducted.Results: Among 621 lung cancer patients infected with SARS-CoV-2, 203 (32.7%) developed pneumonia, and 66 (10.6%) were ≥ grade 2. Multivariate logistic regression analysis showed that diabetes, thoracic radiotherapy, low platelet and low albumin at diagnosis of COVID-19 were significantly associated with all-grade pneumonia. The C-indices of the prediction nomograms in the training group and validation group were 0.702 and 0.673, respectively. Independent predictors of ≥ grade 2 pneumonia were age, KPS, thoracic radiotherapy, platelet and albumin at COVID 19 diagnosis, with C-indices of 0.811 and 0.799 in the training and validation groups. In the thoracic radiotherapy subgroup, 40.8% and 11% patients developed all-grade and ≥grade 2 pneumonia, respectively. The rates in the immunotherapy subgroup were 31.3% and 6.6%, respectively.Conclusion: We developed nomograms predicting the probability of pneumonia in lung cancer patients infected with SARS-CoV-2. The models showed good performance and can be used in the clinical management of COVID-19 in lung cancer patients. Higher-risk patients should be managed with enhanced protective measures and appropriate intervention.Keywords: COVID-19, pneumonia, lung cancer, risk factor, nomogram

Min Liu,1,2 Bo Liu,2 Ziyang Liu,3 Zhen Yang,2 Thomas J Webster,4 Huan Zhou,2 Lei Yang2 1School of Materials Science and Engineering, Hebei University of Technology, Tianjin, People’s Republic of China; 2Center for Health Science and Engineering, Hebei Key Laboratory of Biomaterials and Smart Theranostics, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin, 300131, People’s Republic of China; 3Department of Orthopedics, Tianjin Hospital, Tianjin, People’s Republic of China; 4School of Engineering, Saveetha University, Chennai, IndiaCorrespondence: Huan Zhou; Lei Yang, Center for Health Science and Engineering, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin, 300131, People’s Republic of China, Email zhouhuan@hebut.edu.cn; ylei@hebut.edu.cnIntroduction: Lumbar interbody fusion is widely employed for both acute and chronic spinal diseases interventions. However, large incision created during interbody cage implantation may adversely impair spinal tissue and influence postoperative recovery. The aim of this study was to design a shape memory interbody fusion device suitable for small incision implantation.Methods: In this study, we designed and fabricated an intervertebral fusion cage that utilizes near-infrared (NIR) light-responsive shape memory characteristics. This cage was composed of bisphenol A diglycidyl ether, polyether amine D-230, decylamine and iron oxide nanoparticles. A self-hardening calcium phosphate-starch cement (CSC) was injected internally through the injection channel of the cage for healing outcome improvement.Results: The size of the interbody cage is reduced from 22 mm to 8.8 mm to minimize the incision size. Subsequent NIR light irradiation prompted a swift recovery of the cage shape within 5 min at the lesion site. The biocompatibility of the shape memory composite was validated through in vitro MC3T3-E1 cell (osteoblast-like cells) adhesion and proliferation assays and subcutaneous implantation experiments in rats. CSC was injected into the cage, and the relevant results revealed that CSC is uniformly dispersed within the internal space, along with the cage compressive strength increasing from 12 to 20 MPa.Conclusion: The results from this study thus demonstrated that this integrated approach of using a minimally invasive NIR shape memory spinal fusion cage with CSC has potential for lumbar interbody fusion.Keywords: shape memory, interbody fusion cage, NIR responsive, calcium phosphate cement, minimally invasive

Yuanhang Pan,1,&ast; Di Zhao,1,&ast; Xinbo Zhang,1,&ast; Na Yuan,1 Lei Yang,1 Yuanyuan Jia,2 Yanzhao Guo,3 Ze Chen,1 Zezhi Wang,1 Shuyi Qu,1 Junxiang Bao,4 Yonghong Liu1 1Department of Neurology, Xijing Air Force Medical University, Xi’an, People’s Republic of China; 2Encephalopathy Department No.2, Baoji Hospital of Traditional Chinese Medicine, Baoji, People’s Republic of China; 3Encephalopathy Department No.10, Xi’an Hospital of Traditional Chinese Medicine, Xi’an, People’s Republic of China; 4Department of Aerospace Hygiene, Air Force Medical University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghong Liu, Department of Neurology, Xijing hospital, Air Force Medical University, Xi’an, People’s Republic of China, Tel +86 13991236602, Email liuyhong@fmmu.edu.cn Junxiang Bao, Department of Aerospace Hygiene, Air Force Medical University, Xi’an, People’s Republic of China, Tel +86 02984711241, Email baojunx@fmmu.edu.cnBackground: Excessive daytime sleepiness (EDS) forms a prevalent symptom of obstructive sleep apnea (OSA) and narcolepsy type 1 (NT1), while the latter might always be overlooked. Machine learning (ML) models can enable the early detection of these conditions, which has never been applied for diagnosis of NT1.Objective: The study aimed to develop ML prediction models to help non-sleep specialist clinicians identify high probability of comorbid NT1 in patients with OSA early.Methods: Totally, clinical features of 246 patients with OSA in three sleep centers were collected and analyzed for the development of nine ML models. LASSO regression was used for feature selection. Various metrics such as the area under the receiver operating curve (AUC), calibration curve, and decision curve analysis (DCA) were employed to evaluate and compare the performance of these ML models. Model interpretability was demonstrated by Shapley Additive explanations (SHAP).Results: Based on the analysis of AUC, DCA, and calibration curves, the Gradient Boosting Machine (GBM) model demonstrated superior performance compared to other machine learning (ML) models. The top five features used in the GBM model, ranked by feature importance, were age of onset, total limb movements index, sleep latency, non-REM (Rapid Eye Movement) sleep stage 2 and severity of OSA.Conclusion: The study yielded a simple and feasible screening ML-based model for the early identification of NT1 in patients with OSA, which warrants further verification in more extensive clinical practices.Keywords: obstructive sleep apnea, narcolepsy, machine learning, prediction model, sleep disorder

Mengnan Li,1,2,&ast; Xifeng Yang,1,2,&ast; Ru Li,1,2 Baofeng Wu,1,2 Jinxuan Hao,1,2 Yijie Qi,1,2 Tao Bai,1 Luyang Yang,1 Yi Zhang,3 Yunfeng Liu1,4 1Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China; 4Clinical Research Center of Endocrine and Metabolic Diseases in Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunfeng Liu, Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China, Email nectarliu@163.com Yi Zhang, Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China, Email yizhang313@163.comPurpose: There is evidence that long-term vascular risk remains increased in patients with hyperthyroidism even after normalization of thyroid function, and the mechanisms that regulate this risk are unclear. The aim of this study was to assess how visceral fat area and subcutaneous fat area change after hyperthyroidism treatment, and to further explore the relationship between thyroid hormones, abdominal fat area (visceral fat area and subcutaneous fat area), and lipids.Patients and Methods: 50 patients with newly diagnosed Graves’ disease were selected. Anthropometric parameters (weight, height, body mass index, waist circumference, neck circumference), laboratory parameters (thyroid hormones, lipid metabolism indices), abdominal fat area (visceral fat area and subcutaneous fat area), and drug dose were collected. Measurements were made at baseline, 6 and 12 months after treatment. We used linear mixed-effects models for analysis.Results: The results showed that the following indexes changed significantly at different time points: visceral fat area, subcutaneous fat area, free triiodothyronine, free thyroxine, thyroid stimulating hormone, total cholesterol, high-density lipoprotein, low-density lipoprotein, body weight, neck circumference, body mass index, waist circumference, and drug dose (All P< 0.001). We found that free triiodothyronine and free thyroxine were significantly negatively associated with abdominal fat area (P< 0.01). There was no significant correlation between drug dose and abdominal fat area (P> 0.05). Total cholesterol and low-density lipoprotein were significantly positively associated with abdominal fat area (P< 0.01). However, high-density lipoprotein (P=0.06) was not correlated with abdominal fat area. Moreover, the results showed a significant negative correlation between thyroid hormones and lipids (P< 0.001).Conclusion: After anti-thyroid medicine treatment, patients had elevated visceral fat area and subcutaneous fat area and altered lipid profiles. These changes may be one of the reasons why metabolic and cardiovascular diseases remain increased after thyroid function is restored.Keywords: visceral fat area, subcutaneous fat area, thyroid hormones, lipids, Graves’ disease

Xue Bai,1,2,&ast; LiTing Yang,1,2,&ast; Ruxin Liu,1,2 YuJiao Tang,1,2 Long Yang,1,2 Lingna Ma,1,2 MengFei Chen,2 Ling Zhang2 1Department of Emergency, The Third Clinical Medical College of Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Emergency, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: MengFei Chen; Ling Zhang, Tel +86 13389513801 ; +86 13895318660, Email prayer_821@sina.com; zhangling_7015@sina.comObjective: Cellular pyroptosis is a pro-inflammatory mode of programmed cell death that has been identified in recent years, and studies have shown that the LncRNA SOX2OT regulates myocardial injury during sepsis, but the exact regulatory mechanism is unclear. The aim of this study was to assess the role of SOX2OT in regulating cardiomyocyte injury during sepsis cardiomyopathy.Methods: Rat cardiomyocytes, C57BL/6 mice, and transgenic mice were divided into four groups: control, LPS, LPS+ knockout LncRNA SOX2OT, and LPS+ overexpression LncRNA SOX2OT. Inflammatory factor levels were detected by qPCR. Associated proteins and gene expression were detected by Western blotting and qPCR. Dual luciferase was used to detect the target genes of SOX2OT. Nrf2 and EZH2 knockdown and overexpression cell lines were established, and the expression of related genes was detected by qPCR.Results: Results In this study, we found that SOX2OT knockdown exacerbated LPS-induced levels of inflammatory factors and procalcitoninogen (PCT), and increased the expression of pyroptosis-related proteins and LDH. The results of dual luciferase reporter gene assay showed that EZH2 is the target gene of SOX2OT, and overexpression of SOX2OT decreased the expression of EZH2; we also found that knockdown of EZH2 in H9c2 cells decreased the expression of Nrf2, which was positively correlated with the expression level of NLRP3. Further in vivo results showed that overexpression of SOX2OT attenuated SIMD (sepsis-induced myocardial dysfunction), as evidenced by improved myocardial structural integrity and reduced inflammatory cell infiltration. The expression of pyroptosis-related proteins and LDH was significantly increased in the mice in the LPS group; this effect was reversed by overexpression of SOX2OT, and potentiated by knockdown of SOX2OT.Conclusion: Our data reveal a novel mechanism by which SOX2OT inhibits cardiomyocyte sepsis through the EZH2/Nrf-2/NLRP3 pathway, thereby attenuating septic myocardial injury, which may contribute to the development of new therapeutic strategies.Keywords: SOX2OT, EZH2, Nrf2, sepsis, pyroptosis

Qianghua Quan,1– 3 Haihao Pan,1– 3 Fei Wang,1,2 Siyi Wang,1– 3 Lingli Yang,1– 3 Mixiang Guan,1,2 Quan An1,2 1Research and Development Department, Yunnan Baiyao Group Shanghai Science & Technology Co., Ltd, Shanghai, People’s Republic of China; 2East Asia Skin Health Research Center, Beijing, People’s Republic of China; 3Yunnan Baiyao Group Co. Ltd, Kunming, People’s Republic of ChinaCorrespondence: Haihao Pan; Fei Wang, Email P18811331878@163.com; wangfei@ynbyjk.comPurpose: In the quest for a youthful appearance, women use a variety of anti- aging cosmetics. Defining skin problems is especially important for the selection of anti-aging solutions. However, the skin problems faced by Chinese women at different ages are different. This study aimed at Chinese women aged 20– 40 years old and analyzed facial skin aging characteristics of those with old-perceived age.Patients and Methods: The total of 400 standard facial photographs from Chinese female volunteers aged 20– 40 was assessed by another 126 Chinese women. The facial areas and skin aging characteristics that influenced age estimation were collected at the same time. Skin aging characteristics, including wrinkles, skin tone, pigmentation and pores, were analyzed based on facial photographs. Groupings were made based on deviation of perceived age from chronological age, and skin aging characteristics among groups were compared.Results: The perceived age of Chinese women aged 20– 40 has a moderate correlation with chronological age. Women aged 20– 30 generally had an old-perceived age. Deep skin tone was a prominent problem in this age group, with those who had the older-perceived age observed the darker and redder skin tone. Women aged 31– 40 were perceived partly old but appeared with wrinkle aggravation, as well as deepening of redness, enlarged pores, and increased pigmentation at the mid-face. The perceived older women also had more visible frown lines and darker skin tone at the upper face.Conclusion: The perceived age of Chinese women aged 20– 40 tends to deviate from their chronological age. Women aged 20– 30 with old-perceived age are associated with deep skin tone, even found darker and redder in older-perceived women group, while women aged 31– 40 are associated with wrinkles and deterioration at mid-face area and upper-face problems drive more attention in older-perceived women group.Keywords: perceived age, Chinese female, wrinkles, skin tone, skin aging

Yuxin Bai,1,2 Yanjing Zhu,1 Xiaolie He,1 Ruiqi Huang,1,2 Xu Xu,1 Li Yang,1 Zhaojie Wang,1,2 Rongrong Zhu1,2 1Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital Affiliated to Tongji University, School of Life Science and Technology, Tongji University, Shanghai, 200065, People’s Republic of China; 2Frontier Science Center for Stem Cell Research, Tongji University, Shanghai, 200065, People’s Republic of ChinaCorrespondence: Zhaojie Wang; Rongrong Zhu, Email 2013wangzhaojie@tongji.edu.cn; rrzhu@tongji.edu.cnPurpose: The committed differentiation fate regulation has been a difficult problem in the fields of stem cell research, evidence showed that nanomaterials could promote the differentiation of stem cells into specific cell types. Layered double hydroxide (LDH) nanoparticles possess the regulation function of stem cell fate, while the underlying mechanism needs to be investigated. In this study, the process of embryonic stem cells (ESCs) differentiate to neural progenitor cells (NPCs) by magnesium aluminum LDH (MgAl-LDH) was investigated.Methods: MgAl-LDH with diameters of 30, 50, and 100 nm were synthesized and characterized, and their effects on the cytotoxicity and differentiation of NPCs were detected in vitro. Dot blot and MeRIP-qPCR were performed to detect the level of m6A RNA methylation in nanoparticles-treated cells.Results: Our work displayed that LDH nanoparticles of three different sizes were biocompatible with NPCs, and the addition of MgAl-LDH could significantly promote the process of ESCs differentiate to NPCs. 100 nm LDH has a stronger effect on promoting NPCs differentiation compared to 30 nm and 50 nm LDH. In addition, dot blot results indicated that the enhanced NPCs differentiation by MgAl-LDH was closely related to m6A RNA methylation process, and the major modification enzyme in LDH controlled NPCs differentiation may be the m6A RNA methyltransferase METTL3. The upregulated METTL3 by LDH increased the m6A level of Sox1 mRNA, enhancing its stability.Conclusion: This work reveals that MgAl-LDH nanoparticles can regulate the differentiation of ESCs into NPCs by increasing m6A RNA methylation modification of Sox1.Keywords: mouse embryonic stem cell, neural progenitor cells, layered double hydroxide nanoparticles, size-dependent, differentiation, m6A RNA methylation

Juanjuan Liu,1 Minqin Xu,1 Ling Zhou,1 Li Yang,1 Hong Li,2 Xue Li1 1Department of Obstetrics and Gynecology, Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Radiology, Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Xue Li, Department of Obstetrics and Gynecology, Second Affiliated Hospital of Soochow University, 1055 San Xiang Road, Suzhou, 215004, People’s Republic of China, Tel +8613584834618, Email zlanling@163.comObjective: To investigate the magnetic resonance imaging (MRI) features of women with prior second-trimester pregnancy loss, and to establish a nomogram prediction model for subsequent miscarriage.Methods: A retrospective cohort study of women with prior second-trimester pregnancy loss from January 2018 to December 2021 in Second Affiliated Hospital of Soochow University was performed. A total of 245 patients were included. Data from January 2018 to December 2019 were used to construct the model, and data from January 2020 to December 2021 were used to evaluate the model. Data on maternal demographic characteristics, MRI cervical measurements were extracted. The prediction model was constructed with independent variables determined by multivariate logistic regression analyses. Through receiver-operating characteristic (ROC) curve analysis, the predictive ability of the model for subsequent second trimester pregnancy loss in women was evaluated, and internal validation was performed through validation data.Results: Thin cervix was observed in 77 (31.42%) women with prior second-trimester pregnancy loss, the mean longitudinal diameter of cervical canal on MRI was 11.76± 2.75mm. The model reached a sensitivity of 80%, specificity of 75.90%, positive predictive value (PPV) of 55.80% and negative predictive value of 90.90%; ROC characteristics proved that the model was superior to any single parameter with an AUC of 0.826.Conclusion: Our observations showed that thin cervix and longitudinal diameter of cervical canal reliably predicted second trimester pregnancy loss. We developed and validated a nomogram model to predict the individual probability of second trimester pregnancy loss in the next pregnancy and hopefully improve the prediction and indication of interventions.Keywords: cervical insufficiency, MRI, nomogram, magnetic resonance imaging, CI

Jianlin Ji,1,&ast; Liling Yang,2,&ast; Hanlin Yang,1 Chengxi Zeng,1 Wenjuan Tang,2 Qunfeng Lu1,3 1School of Nursing, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Nursing Department, Children’s Hospital of Shanghai, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Nursing, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qunfeng Lu, Department of Nursing, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China, Email luluroom2004@163.com Wenjuan Tang, Nursing department, Children’s Hospital of Shanghai, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China, Email wjtang2014@163.comBackground: Despite the availability of a considerable number of studies on transitional care, few qualitative studies have synthesized physicians’ perspectives on PICU-to-ward transition to develop a comprehensive transitional care curriculum. The aim of this study is to explore physicians’ perceptions and management of the transition of critically ill children from the PICU to the general ward, with the aim of providing an evidence-based curriculum.Methods: A qualitative study was conducted between July and August 2022. The study involved semi-structured interviews with 11 participants, and data analysis was carried out using NVivo 12.0 software through thematic analysis method.Results: Based on the data analysis, three main themes were identified: recognition of professional roles during transition, difficulties during implementation transitional care and suggestions for improving transitional care.Conclusion: The insights of doctors can be valuable in improving transitional care for critically ill children during PICU-to-Ward transition and in developing relevant curricula. It is essential to introduce standardized clinical pathways and strengthen curricula on critical elements, including communication and follow-up.Keywords: pediatric intensive care unit, pediatricians, transitional care, qualitative study

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

Dan Li,1,&ast; Na Sun,1,&ast; Li Xiang,2 Jingjie Liu,2 Xueying Wang,1 Lin Yang,1,&ast; Shaoping Huang1,&ast; 1Department of Pediatrics, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Neurology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaoping Huang; Lin Yang, Department of Pediatrics, the Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 Xiwu Road, Xi’an, Shaanxi, 710004, People’s Republic of China, Tel +86-18681852505, Email zhengtu1127@163.com; zahp78@163.comObjective: This study aimed to observe the neurophysiological characteristics of type II and type III 5q spinal muscular atrophy (SMA) patients and the changes in peripheral motor nerve electrophysiology after Nusinersen treatment, as well as the influencing factors.Methods: This single-center retrospective case–control study collected clinical data and peripheral motor nerve CMAP parameters from 42 5qSMA patients and 42 healthy controls at the Second Affiliated Hospital of Xi’an Jiaotong University (January 2021 to December 2022). It evaluated changes in motor function and CMAP amplitude before and after Nusinersen treatment.Results: Our investigation encompassed all symptomatic and genetically confirmed SMA patients, consisting of 32 type II and 10 type III cases, with a median age of 57 months (29.5 to 96 months). Comparative analysis with healthy controls revealed substantial reductions in CMAP amplitudes across various nerves in both type II and type III patients. Despite the administration of Nusinersen treatment for 6 or 14 months to the entire cohort, discernible alterations in motor nerve amplitudes were not observed, except for a significant improvement in younger patients (≤ 36 months) at the 14-month mark. Further scrutiny within the type II subgroup unveiled that individuals with a disease duration ≤ 12 months experienced a noteworthy upswing in femoral nerve amplitude, a statistically significant difference when compared to those with > 12 months of disease duration.Conclusion: Motor nerve amplitudes were significantly decreased in type II and type III 5q SMA patients compared to healthy controls. Nusinersen treatment showed better improvement in motor nerve amplitudes in younger age groups and those with shorter disease duration, indicating a treatment-time dependence.Keywords: 5q spinal muscular atrophy, neurophysiology, peripheral motor nerve, Nusinersen

Xiaohong Chen,1,&ast; Shiqi Zhou,2,&ast; Lin Yang,1 Qianqian Zhong,1 Hongguang Liu,3 Yongjian Zhang,1 Hanyi Yu,2 Yongjiang Cai1 1Center of Health Management, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 2School of Future Technology, South China University of Technology, Guangzhou, People’s Republic of China; 3Center of Health Management, Huazhong University of Science and Technology Union Hospital (Nanshan Hospital), Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongjiang Cai, Center of Health Management, Peking University Shenzhen Hospital, Shenzhen, 518036, People’s Republic of China, Email caiyj2000@sina.cn Hanyi Yu, School of Future Technology, South China University of Technology, Guangzhou, People’s Republic of China, Email yuhanyi@scut.edu.cnPurpose: The purpose of this study is to explore the independent-influencing factors from normal people to prediabetes and from prediabetes to diabetes and use different prediction models to build diabetes prediction models.Methods: The original data in this retrospective study are collected from the participants who took physical examinations in the Health Management Center of Peking University Shenzhen Hospital. Regression analysis is individually applied between the populations of normal and prediabetes, as well as the populations of prediabetes and diabetes, for feature selection. Afterward,the independent influencing factors mentioned above are used as predictive factors to construct a prediction model.Results: Selecting physical examination indicators for training different ML models through univariate and multivariate logistic regression, the study finds Age, PRO, TP, and ALT are four independent risk factors for normal people to develop prediabetes, and GLB and HDL.C are two independent protective factors, while logistic regression performs best on the testing set (Acc: 0.76, F-measure: 0.74, AUC: 0.78). We also find Age, Gender, BMI, SBP, U.GLU, PRO, ALT, and TG are independent risk factors for prediabetes people to diabetes, and AST is an independent protective factor, while logistic regression performs best on the testing set (Acc: 0.86, F-measure: 0.84, AUC: 0.74).Conclusion: The discussion of the clinical relationships between these indicators and diabetes supports the interpretability of our feature selection. Among four prediction models, the logistic regression model achieved the best performance on the testing set.Keywords: prediabetes, prediction model, physical examination, machine learning, regression analysis

Liqun Yang,1– 3 Zhimei Zhang,3 Yunfeng Zhen,3 Jing Feng,3 Jinhu Chen,3 Guangyao Song1– 3 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China; 2Hebei Key Laboratory of Metabolic Disease, Shijiazhuang, Hebei Province, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: Guangyao Song, Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China, Tel +86-0311-8598-8556, Email sguangyao2@163.comPurpose: Energy metabolism is regulated by SIRT3, no research has been done on the connection between lipid metabolism in the oral fat test and SIRT3 polymorphism. Thus, we conducted a case-control study to investigate the connection between postprandial lipid and SIRT3 polymorphism.Patients and Methods: 402 non-obese Chinese subjects were enrolled and their postprandial lipid response to oral fat tolerance test (OFTT) was observed to understand the relationship between rs11246020 gene and postprandial triglyceride metabolism.Results: In a binary logic regression model, a protective effect of the T allele of the rs11246020 SIRT3 for postprandial hypertriglyceridemia was shown (OR=0.417, 95% CI = 0.219– 0.794, p=0.008). Compared to the CC genotype, individuals with the TT+CT variant of the rs11246020 SIRT3 gene demonstrated significantly lower levels of homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.04), postprandial plasma glucose (PPG) (p=0.037), fasting plasma glucose (FPG) (p=0.02), and 4-hour triglyceridemia (Tg) (p=0.032).Conclusion: The C allele of rs11246020 SIRT3 gene may be a risk factor to increased possibility of postprandial triglyceridemia after an oral fat test, which involved in the mechanism of glucose and insulin metabolism.Keywords: sirtuin, postprandial hypertriglyceridemia, insulin resistance, genetics

Jiangling Wang,1,2,&ast; Lijuan Yang,3,&ast; Wei Liu,1 Chaogang Wei,1 Junkang Shen1 1Department of Radiology, The Second Affiliated Hospital of Soochow University, Soochow, Jiangsu, People’s Republic of China; 2Department of Physical Diagnosis, Huadong Sanatorium, Wuxi, Jiangsu, People’s Republic of China; 3Department of Geriatric, Huadong Sanatorium, Wuxi, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junkang Shen; Chaogang Wei, Department of radiology, The Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Soochow, 215004, People’s Republic of China, Email shenjunkang@suda.edu.cn; weichaogang1122@163.comObjective: Previous research on the correlation between thyroid function and carotid plaque has revealed conflicting results, possibly attributable to the sensitivity of thyroid hormone indices. In this study, we aimed to analyze the association between thyroid hormone sensitivity indices and the risk of carotid plaque development in a Chinese health check-up population.Methods: A total of 19,388 health check-up subjects were included in this study (mean age: 50.78± 10.17 years). Central sensitivity to thyroid hormone was evaluated using the thyroid feedback quantile-based index (TFQI), the Chinese-referenced parametric TFQI (PTFQI), the TSH index (TSHI), and the thyrotropin thyroxine resistance index (TT4RI), while peripheral sensitivity to thyroid hormone was assessed by free triiodothyronine/free thyroxine (FT3/FT4) ratio. Multivariable logistic regression analyses were performed to detect the association between thyroid hormone sensitivity indices and carotid plaque risk, and subgroup analysis was also conducted to explore this association stratified by sex, age, obesity, and the status of smoking, drinking, diabetes, hypertension and dyslipidemia.Results: Among the 19,388 participants, 3753 (19.4%) had carotid plaque. In multivariable adjustment models, the risk of carotid plaque was positively associated with TSHI (odds ratio [OR]: 1.23; 95% confidence interval [CI]: 1.18~1.28), TT4RI (OR: 1.28; 95% CI: 1.23~1.33), TFQI (OR: 1.06; 95% CI: 1.02~1.10), and PTFQI (OR: 1.11; 95% CI: 1.07~1.16), respectively. Conversely, the risk of carotid plaque was negatively correlated with FT3/FT4 (OR: 0.94; 95% CI: 0.90~0.98). In stratified analyses, all thyroid hormone sensitivity indices significantly increased the risk of carotid plaque especially in females, subjects< 65 years, non-obese individuals, and those without current smoking, drinking, diabetes, hypertension and dyslipidemia.Conclusion: In Chinese health check-up populations, a considerable connection between reduced sensitivity to thyroid hormones and carotid plaque has been observed, especially in females, those younger than 65 years, non-obese individuals, and those without any current smoking, drinking, diabetes, hypertension, or dyslipidemia.Keywords: carotid plaque, thyroid hormone sensitivity, euthyroid, resistance to thyroid hormone, Chinese population

Yiyang Li,1,&ast; Jiali Chen,1,&ast; Xingping Quan,1 Ying Chen,2 Yan Han,1 Jinfen Chen,1 Li Yang,1 Youhua Xu,3 Xu Shen,4 Ruibing Wang,1,5 Yonghua Zhao1,5 1Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Taipa, Macau SAR, People’s Republic of China; 2School of Health Economics and Management, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao SAR, People’s Republic of China; 4Jiangsu Key Laboratory of Drug Target and Drug for Degenerative Diseases, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 5Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghua Zhao, Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Taipa, Macao SAR, People’s Republic of China, Tel +853-88224877, Fax +853-28841358, Email yonghuazhao@um.edu.moBackground: Ischemic stroke (IS) causes tragic death and disability worldwide. However, effective therapeutic interventions are finite. After IS, blood–brain barrier (BBB) integrity is disrupted, resulting in deteriorating neurological function. As a novel therapeutic, extracellular vesicles (EVs) have shown ideal restorative effects on BBB integrity post-stroke; however, the definite mechanisms remain ambiguous. In the present study, we investigated the curative effects and the mechanisms of EVs derived from bone marrow mesenchymal stem cells and brain endothelial cells (BMSC-EVs and BEC-EVs) on BBB integrity after acute IS.Methods: EVs were isolated from BMSCs and BECs, and we investigated the therapeutic effect in vitro oxygen-glucose deprivation (OGD) insulted BECs model and in vivo rat middle cerebral artery occlusion (MCAo) model. The cell monolayer leakage, tight junction expression, and metalloproteinase (MMP) activity were evaluated, and rat brain infarct volume and neurological function were also analyzed.Results: The administration of two kinds of EVs not only enhanced ZO-1 and Occludin expressions but also reduced the permeability and the activity of MMP-2/9 in OGD-insulted BECs. The amelioration of the cerebral infarction, BBB leakage, neurological function deficits, and the increasing ZO-1 and Occludin levels, as well as MMP activity inhibition was observed in MCAo rats. Additionally, the increased levels of Caveolin-1, CD147, vascular endothelial growth factor receptor 2 (VEGFR2), and vascular endothelial growth factor A (VEGFA) in isolated brain microvessels were downregulated after EVs treatment. In vitro, the employment of Caveolin-1 and CD147 siRNA partly suppressed the expressions of VEGFR2, VEGFA and MMP-2/9 activity and reduced the leakage of OGD insulted BECs and enhanced ZO-1 and Occludin expressions.Conclusion: Our study firstly demonstrates that BEC and BMSC-EVs administrations maintain BBB integrity via the suppression of Caveolin-1/CD147/VEGFR2/MMP pathway after IS, and the efficacy of BMSC-EVs is superior to that of BEC-EVs. Keywords: extracellular vesicles, ischemic stroke, Caveolin-1, CD147, matrix metalloproteinase, VEGFR2, blood-brain barrier

Xue-Mei Liu,1,2,&ast; Liu Yang,1,2,&ast; Qi-Bin Yang1 1Department of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, 637000, People’s Republic of China; 2Department of Clinical Medicine, Graduate School of North Sichuan Medical College, Nanchong, Sichuan Province, 637000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi-Bin Yang, Department of Rheumatology and Immunology, Affiliated Hospital, North Sichuan Medical College, 1 Maoyuannan Road, Nanchong, Sichuan Province, 637000, People’s Republic of China, Tel +86-817-259-8221, Email yangqb_001@163.comAbstract: Rheumatic disease is a disease which is not yet fully clarified to etiology and also involved in a local pathological injury or systemic disease. With the continuous improvement of clinical medical research in recent years, the development process of rheumatic diseases has been gradually elucidated; with the intensely study of epigenetics, it is realized that environmental changes can affect genetics, among which histone acetylation is one of the essential mechanisms in epigenetics. Histone deacetylases (HDACs) play an important role in regulating gene expression in various biological processes, including differentiation, development, stress response, and injury. HDACs are involved in a variety of physiological processes and are promising drug targets in various pathological conditions, such as cancer, cardiac and neurodegenerative diseases, inflammation, metabolic and immune disorders, and viral and parasitic infections. In this paper, we reviewed the roles of HDACs in rheumatic diseases in terms of their classification and function.Keywords: histone deacetylase, histone deacetylase inhibitor, rheumatic diseases

Jie Cheng,1 Ya Liu,2 Shaojun Li,1 Kaibin Pu,1 Lin Yang,1 Liping Tan1 1Department of Emergency, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China; 2Department of Pediatrics, Chongqing Youyoubaobei Women and Children’s Hospital, Chongqing, 401147, People’s Republic of ChinaCorrespondence: Liping Tan, Tel +86-23-63630194, Email tanlp0825@hotmail.comObjective: Third-generation cephalosporin-resistant (3GC-R) bloodstream infection (BSI) is associated with poor prognosis. We investigated the incidence of and risk factors for 3GC-R Escherichia coli (E. coli) BSI in children.Methods: Patients with E. coli BSIs who were hospitalized at the Children’s Hospital of Chongqing Medical University were retrospectively enrolled. Univariate and multivariate logistic regression analyses were used to identify the independent risk factors for 3GC-R BSI.Results: Two hundred fifty-two children with E. coli BSIs were enrolled. The mortality rate was 11.51% (29/252). The infection rate of 3GC-R E. coli was 48.81% (123/252), and the incidence of E. coli BSI during hospitalization was 18.58 per 1000 person-days. Approximately half (47.22%, 119/252) of the children were infected with extended-spectrum beta-lactamases (ESBLs) produced by E. coli. More than one-third (37.30%, 94/252) of the children were unnecessarily administrated carbapenems. According to our logistic regression analysis, a history of carbapenem administration, an elevated Pediatric Sequential Organ Failure Assessment (pSOFA) score ≥ 2, and antimicrobial agent administration before blood culture were independently associated with 3GC-R BSI (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.08– 3.94, P=0.029; OR 2.00, 95% CI 1.10– 3.71, P=0.025, OR 1.86, 95% CI 1.02– 3.42, P=0.044, respectively).Conclusion: In this study, the incidence of 3GC-R E. coli BSI among children was retrospectively evaluated. Patients with a history of carbapenem administration, an elevated pSOFA score ≥ 2 and who were administrated antimicrobial agents before blood culture had an increased risk of 3GC-R E. coli BSI.Keywords: third-generation cephalosporin-resistant, inappropriate use of carbapenems, Escherichia coli, bloodstream infection, children

Lingrong Yang, Jing Guo, Fu Xiong Sichuan Provincial Maternity and Child Health Care Hospital, Women and Children’s Hospital of Chengdu Medical College, Sichuan, Chengdu, 610045, People’s Republic of ChinaCorrespondence: Fu Xiong, Email drfuxiong@163.comBackground: This study aims to evaluate the immunological features of gastrointestinal (GI) bleeding in children with Henoch-Schönlein purpura (HSP).Study Design: This retrospective study was conducted on children with HSP. Demographic and clinical data were collected, including serum immunoglobulin (Ig) levels, complement C3 and C4 levels, and lymphocyte subtype percentage.Results: A total of 446 hospitalized children had HSP. Eighty-six children with HSP had GI bleeding, 114 had proteinuria, and 107 had hematuria. Lower arthralgia, prolonged glucocorticoid use, increased white blood cell counts, elevated neutrophils and neutrophil-to-lymphocyte ratio, reduced IgG and C3 levels, elevated CD19+ cell percentage, and reduced CD3+ cell and natural killer cell percentages were associated with GI bleeding risk in patients with HSP. Multivariate regression analysis revealed that arthralgia, glucocorticoid use, increased neutrophil percentage, reduced IgG and C3 levels, and increased CD19+ cell percentage were independent predictors of GI bleeding. Further analysis indicated that the combination of C3 and CD19+ cell percentages had a high predictive ability for GI bleeding in children with HSP.Conclusion: This study indicated that reduced C3 and increased CD19+ cell percentages contributed to the development of GI bleeding in children with HSP. Specific immunologic profiles may be strongly correlated with GI bleeding risk in children with HSP.Keywords: children, complement, gastrointestinal bleeding, Henoch-Schönlein purpura, lymphocyte subtype

Liu Yang, Zhe Ma Department of Medical Ultrasound, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan City, Shandong Province, People’s Republic of ChinaCorrespondence: Zhe Ma, Department of Medical Ultrasound, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766, Jingshi Road, Jinan City, Shandong Province, 250014, People’s Republic of China, Tel +86-13969033555, Email mazhe315@163.comObjective: To establish a good predictive model using a deep-learning (DL)-based three-dimensional (3D) super-resolution ultrasound images for the diagnosis of benign and malignant breast lesions.Methods: This retrospective study included 333 patients with histopathologically confirmed breast lesions, randomly split into training (N=266) and testing (N=67) datasets. Eight models, including four deep learning models (ORResNet101, ORMobileNet_v2, SRResNet101, SRMobileNet_v2) and four machine learning models (OR_LR, OR_SVM, SR_LR, SR_SVM), were developed based on original and super-resolution images. The best performing model was SRMobileNet_v2, which was used to construct a nomogram integrating clinical factors. The performance of nomogram was evaluated using receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and calibration curves.Results: SRMobileNet_v2, MobileNet_V2 based on super-resolution ultrasound images, had the best predictive performance in four traditional machine learning models and four deep learning models, with AUC improvements of 0.089 and 0.031 in the training and testing sets, relative to the ORMobileNet_v2 model based on original ultrasound images. The deep-learning nomogram was constructed using the SRMobileNet_v2 model score, tumor size, and patient age, resulting in superior predictive efficacy compared to the nomogram without the SRMobileNet_v2 model score. Furthermore, it demonstrated favorable calibration, discrimination, and clinical utility in both cohorts.Conclusion: The diagnostic prediction model utilizing super-resolution reconstructed ultrasound images outperforms the model based on original images in distinguishing between benign and malignant breast lesions. The nomogram based on super-resolution ultrasound images has the potential to serve as a reliable auxiliary diagnostic tool for clinicians, exhibiting superior predictive performance in distinguishing between benign and malignant breast lesions.Keywords: deep learning, radiomics, machine learning, breast lesion, super-resolution

Weiliang Zhang,1,&ast; Xiaoqin Cao,2,&ast; Lu Yang,3 Yajian Duan,1 Wei Zhang1 1Department of Ophthalmology, Shanxi Bethune Hospital, Taiyuan, People’s Republic of China; 2Department of General Surgery, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Ophthalmology, Changzhi Aier Eye Hospital, Changzhi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Yang, Changzhi Aier Eye Hospital, Luyangmen Middle Road, Luzhou District, Changzhi, 046000, People’s Republic of China, Tel +86-3558128120, Email luyang1494@163.comObjective: To investigate the effectiveness of intense pulsed light (M22) in treating patients with meibomian gland dysfunction (MGD) caused by demodex mites.Methods: A total of 100 patients (100 eyes) diagnosed with demodex mites through microscopic examination at Shanxi Bethune Eye Clinic between June 2021 and May 2023 were selected using convenience sampling. The patients were randomly divided into two groups: an experimental group (n=50) and a control group (n=50). The control group received comprehensive treatment consisting of artificial tears, warm compress, anti-inflammatory eye ointment, hypochlorous acid cleansing, okra cotton pad, and meibomian gland massage. In addition to the comprehensive treatment, the experimental group received intense pulsed light (M22) therapy. After 8 weeks of treatment, the mite clearance rate and cure rate of dry eye were measured for both groups. The recurrence rate of dry eye was also observed 4 weeks after discontinuing M22 treatment.Results: The experimental group achieved a mite clearance rate of 88.0%, while the control group had a rate of 58.0%, with a statistically significant difference (χ2 = 5.43, P = 0.017). Regarding the cure rate of dry eye, the experimental group showed a rate of 92.0%, while the control group had a rate of 82.0%, with a statistically significant difference (χ2 = 3.61, P = 0.021). In terms of the recurrence rate of dry eye, the experimental group exhibited a rate of 13.04%, while the control group had a rate of 26.83%, with a statistically significant difference (χ2 = 4.18, P = 0.016).Conclusion: Intense pulsed light (M22) demonstrated superior efficacy in eradicating demodex mites, treating dry eye, and maintaining the treatment’s effectiveness compared to comprehensive treatment with medication in patients suffering from meibomian gland dysfunction with demodex mites.Keywords: intense pulsed light, meibomian gland dysfunction, dry eye

Chunmei Yang,1,&ast; Xiaoling Che,1,&ast; Yu Zhang,2 Didi Gu,1 Guidong Dai,1 Jian Shu,1 Lu Yang1 1Department of Radiology, The Affiliated Hospital of Southwest Medical University, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan Province, People’s Republic of China; 2Department of Radiology, The First People’s Hospital of Yibin, Yibin, 644000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Shu; Lu Yang, Department of Radiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, People’s Republic of China, Tel +86 0830-18980253083 ; +86 0830-2504762, Email shujiannc@163.com; yanglu@swmu.edu.cnBackground: Development of versatile nanoplatform still remains a great challenge due to multistep synthesis and complicated compositions. Therefore, it is significant to develop a facile method to synthesize a nanocomposite to achieve multimodal imaging and even imaging-guided cancer therapeutics.Methods and Results: In our study, hyaluronic acid-functionalized iron (II) tungstate nanoparticles (HA-FeWO4 NPs) were successfully synthesized as a versatile nanoplatform by a facile one-pot hydrothermal procedure. The formed multifunctional HA-FeWO4 NPs were investigated via a series of characterization techniques, which demonstrated good biocompatibility, excellent dispersion, low cytotoxicity, active tumor-targeting ability and high photothermal efficiency. Furthermore, tumor was clearly visualized by HA-FeWO4 NPs with multimodal imaging of infrared thermal imaging, magnetic resonance imaging, computed tomography imaging in 4T1 tumor bearing mice. More importantly, HA-FeWO4 could achieve multimodal imaging-guided photothermal therapy of 4T1 tumors.Conclusion: The constructed HA-FeWO4 NPs have great potential as ideal nanotheranostic agents for multimodal imaging and even imaging-guided cancer theranostics in biological systems.Keywords: theranostics, multimodal imaging, photothermal therapy, diagnostic imaging, nanomedicine

Yun Zhao,1,&ast; Lijun Zhao,1,&ast; Zhaohuang Wang,1 Shuhui Cui,1 Chenchen Ren,2 Li Yang,2 Yang Bai,2 Yuanhang Zhu,2 Jingyan Xie,3 Yujuan Li,3 Xiaoqing Wu,3 Jing Feng,3 Shanqing Man,4 Longmei Huang,4 Xiaoqi Li,4 Xiaotian Yu,4 Jianliu Wang1 1Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, National Clinical Research Center for Obstetrics and Gynecology, Zhengzhou Key Laboratory of Cervical Disease, Zhengzhou Key Laboratory of Endometrial Disease Prevention and Treatment, Zhengzhou, Henan, People’s Republic of China; 3Department of Obstetrics and Gynecology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Hangzhou New Horizon Health Technology Co. Ltd, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianliu Wang, Department of Obstetrics and Gynecology, Peking University People’s Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Tel +8618901086568, Email wangjianliu1203@163.comObjective: The objective of this study is to assess the clinical performance of a urine-based high-risk human papillomavirus (hrHPV) test for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+).Methods: Between September and December 2021, women aged 20 to 65 years referred to colposcopy clinic were prospectively recruited at three clinical centers in China. Paired urine and cervical specimens from all enrolled women were obtained for hrHPV DNA fluorescence quantitative PCR test. The results of liquid-based cytology (LBC), colposcopy and diagnostic biopsies were collected. We evaluated the sensitivity and specificity for CIN and assessed the agreement/kappa value.Results: A total of 732 women (median age, 40 years) with valid results were included in the study, and 130 (17.8%) women were histologically confirmed as CIN2+. The sensitivity of urine and cervical test for CIN2+ and CIN3+ were 87.69% and 85.45%, respectively. The specificity of urine test performed better than cervical test in women with

Yang Han,1 Bo Tang,2 Xian-Miao Li,3 Guo-Song-Rui Yang,4 Li Yang4 1Department of Finance and Accounting, School of Economics and Management, Anhui University of Science and Technology, Huainan, 232001, People’s Republic of China; 2Department of Management, Birmingham Business School, University of Birmingham, Birmingham, B15 2TT, UK; 3Department of Business and Administration, School of Economics and Management, Anhui University of Science and Technology, Huainan, 232001, People’s Republic of China; 4Department of Management Science and Engineering, School of Economics and Management, Anhui University of Science and Technology, Huainan, 232001, People’s Republic of ChinaCorrespondence: Yang Han, Department of Finance and Accounting, School of Economics and Management, Anhui University of Science and Technology, No. 168 of Taifeng Street, Shannan District, Huainan, 232001, People’s Republic of China, Tel +86 15375052657, Email yanghan3134hes@163.comBackground: This study aims to investigate how a team can be resilient in the face of crisis and adversity.Methods: This empirical study adopted a quantitative research method. The data were collected by questionnaire survey, and the stats analysis package in R language and AMOS 23 were used for empirical analysis of 98 teams. Based on complex adaptive system theory and conservation of resources theory, this study was constructed the theoretical framework of “environmental influence — team exchange — team resilience” with informational team faultline (ITF) as independent variable, team leader member exchange (TLMX) and team member exchange (TMX) as mediating and moderating variables, and team resilience as dependent variable in the context of Chinese culture.Results: We found that the ITF had a significant negative effect on the team resilience. TLMX and TMX played partial mediating role between ITF and team resilience. In addition, TLMX and TMX played moderating role between ITF and team resilience, that is, weakening the negative influence of ITF on team resilience.Conclusion: This study contributes to clarify the mechanism of the influence of ITF on team resilience, and provide reference for team leaders to improve team resilience in the face of adversity.Keywords: informational team faultline, team leader member exchange, team member exchange, team resilience, Chinese culture context

Jun Wang,1,&ast; Hongmei Chen,2,&ast; Lin Yang,2 Xiuli Yu,3 Dandan Zhang,3 Qinghua Zhao,1 Mingzhao Xiao4 1Department of Nursing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Qinggang Senior Care Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingzhao Xiao, Department of Urology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Chongqing, 400016, People’s Republic of China, Tel +8613608399433, Fax +86-23-89012206, Email mingzhaoxiao@cqmu.edu.cnAbstract: This paper aims to describe a randomized controlled trial protocol evaluating the effectiveness, cost, and process of a stress process model-based program in dementia caregiving (DeCare-SPM) for family caregivers. Family caregivers of individuals with dementia will be recruited from memory clinics and community settings and randomly assigned to either DeCare-SPM or usual care. DeCare-SPM comprises three face-to-face sessions (ie, problem-based coping, emotion-based coping, meaning-based coping), and a fourth session (ie, social support) including weekly telephone-based consultation for four weeks and then monthly face-to-face boosters. Outcomes will be measured at baseline (T0), and at one (T1), three (T2), and six months (T3). The primary outcome is positive aspects of caregiving and secondary outcomes are caregiving (ie, sense of competence, caregiver burden, social support, anxiety, depression, and quality of life), dementia-related (ie, care dependency, neuropsychiatric symptoms, and quality of life), and stress-related biomarkers of blood and saliva. In addition, process and economic evaluations will be performed. Mixed-effects models will be used to assess intervention effects. Content analysis will be performed on the qualitative data. This paper described the protocol for comprehensive evaluation of the effectiveness, cost, and process of the theory-driven DeCare-SPM to inform how and why interventions work. It highlights the need to reduce challenges and enhance the positive aspects of dementia care. The DeCare-SPM will provide evidence-based insights into how to support and empower family caregivers in their important roles, thereby, leading to improved dementia care.Keywords: Alzheimer’s disease, stress coping, informal caregivers, community, psychosocial

Jing Yang,1,2,&ast; Jinlu Shang,1,2,&ast; Liuxuan Yang,1,2,&ast; Daiqing Wei,3 Xia Wang,1 Qinmin Deng,2 Zhirong Zhong,4 Yun Ye,1 Meiling Zhou1 1Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Department of Clinical Pharmacy, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Department of Orthopaedics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meiling Zhou, Email meilzhou@163.comAbstract: Honokiol (HNK) is a small-molecule polyphenol that has garnered considerable attention due to its diverse pharmacological properties, including antitumor, anti-inflammatory, anti-bacterial, and anti-obesity effects. However, its clinical application is restricted by challenges such as low solubility, poor bioavailability, and rapid metabolism. To overcome these limitations, researchers have developed a variety of nano-formulations for HNK delivery. These nano-formulations offer advantages such as enhanced solubility, improved bioavailability, extended circulation time, and targeted drug delivery. However, existing reviews of HNK primarily focus on its clinical and pharmacological features, leaving a gap in the comprehensive evaluation of HNK delivery systems based on nanotechnology. This paper aims to bridge this gap by comprehensively reviewing different types of nanomaterials used for HNK delivery over the past 15 years. These materials encompass vesicle delivery systems, nanoparticles, polymer micelles, nanogels, and various other nanocarriers. The paper details various HNK nano-delivery strategies and summarizes their latest applications, development prospects, and future challenges. To compile this review, we conducted an extensive search using keywords such as “honokiol”, “nanotechnology”, and “drug delivery system” on reputable databases, including PubMed, Scopus, and Web of Science, covering the period from 2008 to 2023. Through this search, we identified and selected approximately 90 articles that met our specific criteria. Keywords: honokiol, nanotechnology, drug delivery, targeting, antitumor, bioavailability

Linlan Yang,1,&ast; Kaijiong Zhang,2,&ast; Dongming Zheng,1 Yuxin Bai,1 Daifan Yue,1 Lichun Wu,2 Han Ling,2 Sujiao Ni,2 Haimin Zou,2 Bo Ye,2 Chang Liu,2 Yao Deng,2 Qiancheng Liu,3 Yan Li,1 Dongsheng Wang1,2 1College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Department of Clinical Laboratory of Mianyang People’s Hospital, Mianyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongsheng Wang, Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China, Email wangdongshengnc@163.com Yan Li, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China, Email Liliana@cdutcm.edu.cnAbstract: In addition to hemostasis and coagulation, years of studies have proved that platelets are involved in the whole process of tumor progression, including tumor invasion, intravasation, extravasation, and so on. It means that this property of platelets can be used in anti-tumor therapy. However, traditional platelet-based antitumor drugs often cause autologous platelet damage due to lack of targeting, resulting in serious side effects. Therefore, the researchers designed a variety of anti-tumor drug delivery systems based on platelets by targeting platelets or platelet membrane coating. The drug delivery systems have special response modes, which is crucial in the design of nanoparticles. These modes enhance the targeting and improve the anti-tumor effect. Here, we present a review of recent discoveries in the field of the crosstalk between platelets and tumors and the progress of platelet-based anti-tumor nanoparticles.Keywords: platelet, tumor, targeted platelet, platelet membranes, stimuli-responsive drug delivery system, nanoparticle

Shuyun Zhang,1,&ast; Lijuan Wu,1,&ast; Xue Li,1 Li Yang,1 Sujuan Shen,1 Hong Shen,1 Dan Zhao,2 Lin Qi2,3 1Center of Reproductive Medicine, The Second Affiliated Hospital of Soochow University, Su Zhou, People’s Republic of China; 2Precision Medicine Center, The Second Affiliated Hospital of Soochow University, Su Zhou, People’s Republic of China; 3State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, 215000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Qi, Precision Medicine Center, The Second Affiliated Hospital of Soochow University, Su Zhou, People’s Republic of China, Tel +86-13962187070, Email drhuan@126.comPurpose: Karyotype analysis of villus chromosomes in spontaneous abortion by high-throughput ligation-dependent probe amplification (HLPA) was performed to explore relationship between spontaneous abortion and chromosomal abnormalities in spontaneous abortion tissues.Patients and Methods: The karyotypes of chromosomes of villus tissues from 516 patients with spontaneous abortion who were admitted to our hospital between 2014 and 2019 were analyzed. The data were grouped by the age (ie, ≤ 29, 30– 35, and ≥ 36 years old) in which embryonic chromosomal abnormality rate, and abnormal distribution of chromosome number in abortion tissue of 294 patients.Results: The examination of 516 samples of spontaneous abortion tissues showed that the chromosomes of 294 samples were abnormal, and the abnormality rate was 60.97%. Among 294 samples with chromosomal abnormalities, 136 (89.47%) samples had numerical chromosomal abnormalities, 15 (9.87%) samples had structural chromosomal abnormalities, and 1 (0.07%) sample had uniparental disomy. A total of 308 couples voluntarily underwent peripheral blood chromosome analysis. The results showed that 56 couples had abnormality in one or both spouses, and rate of embryonic chromosomal abnormality in these 26 cases with chromosomal abnormalities was 100%.Conclusion: Numerical and structural chromosomal abnormalities are among the important causes of embryonic arrest, while the increase in age could also be a high-risk factor for embryonic chromosomal abnormality. Therefore, examination of the karyotypes of embryo chorionic villus may help understand the reasons of embryonic arrest, which could provide important guidance for more genetic counseling for patients with early spontaneous abortion, as well as improving the preconception preparation.Keywords: spontaneous abortion, villus tissue, HLPA test, chromosomal abnormality

Wei Cheng,1 Aiyuan Zhou,2 Yuqin Zeng,1 Ling Lin,1 Qing Song,1 Cong Liu,1 Zijing Zhou,1 Yating Peng,1 Min Yang,1 Lizhen Yang,1 Yan Chen,1 Shan Cai,1 Ping Chen1 1Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital; Research Unit of Respiratory Disease; Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of ChinaCorrespondence: Ping Chen, Department of Pulmonary and Critical Care Medicine, the Second Xiangya Hospital; Research Unit of Respiratory Disease; Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Tel +86-13873115563, Fax +86 731-85295848, Email pingchen0731@csu.edu.cnBackground: The revised Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 group ABE classification has undergone major modifications, which can simplify clinical assessment and optimize treatment recommendations for Chronic Obstructive Pulmonary Disease (COPD). However, the predictive value of the new grouping classification for prognosis is worth further exploration. We aimed to compare the prediction of hospitalization and mortality between this new GOLD group 2023 ABE classification and the earlier 2017 ABCD classification in a Chinese COPD cohort.Methods: Data from 2,499 outpatients with COPD, who first registered in the RealDTC study of Second Xiangya Hospital from December 2016 to December 2019, were collected prospectively and assessed retrospectively. Patients were followed up on all-cause mortality until October 2022 or death.Results: : Of the 2,499 patients with COPD, the risk of hospitalization during the first-year follow-up was higher in group E than in groups A and B. The mortality was higher in group E than in groups A and B, and group B was higher than group A. No differences were seen in the area under the curve (AUC) of 2017 vs 2023 GOLD grouping to predict hospitalization. The time-dependent AUC and concordance index for predicting mortality is slightly higher in the GOLD 2017 ABCD than in the 2023 ABE groups. The new GOLD 12-subgroup (1A– 4E) classification combining the GOLD 1– 4 staging and grouping performed similarly discriminate predictive power for mortality to the GOLD 2017 16-subgroup (A1– 4D) classification.Conclusion: The risk of hospitalization during the first-year follow-up was higher in group E than in groups A and B. The all-cause mortality increased gradually from GOLD group A to E. The GOLD 2023 classification based on ABE groups did not predict mortality better than the earlier 2017 ABCD classifications.Keywords: COPD, mortality, hospitalization, GOLD 2023

Yao Yao,1,&ast; Liu Yang,1,&ast; Zhe Zhang,1,&ast; Binbin Wang,1 Baisui Feng,1 Zhanju Liu1,2 1Department of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, 450014, People’s Republic of China; 2Department of Gastroenterology, the Shanghai Tenth People’s Hospital of Tongji University, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhanju Liu; Baisui Feng, Tel +86-18917683431 ; +86-18756585626, Email fbsktz@163.com; fengbs@zzu.edu.cnBackground: Anti-TNF medications are the first-line treatment for Crohn’s Disease (CD), despite the fact that a significant portion of the population continues to be ineffectively treated. This research aims to discover accurate intervention targets for the follow-up of anti-TNF non-responders using bioinformatics technology.Methods: GSE16879, GSE111761, and GSE52746 retrieved from the GEO database. Unbiased differentially expressed genes (DEGs) were discovered utilizing the limma and RobustRankAggreg (RRA) tools. Then, we used weighted gene co-expression network analysis (WGCNA) to identify the module most strongly associated with non responders and subjected this module to Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis with overlapping genes of the DEGs. GSEA analysis applied to check the results of GO and KEGG. Using the Cytoscape program, the protein-protein interaction (PPI) network was constructed. The software’s MCODE addon and CytoHubba addon was used to find the most important modules and the hub genes. Subsequently, we employed reverse transcription-polymerase chain reaction (RT-PCR) to confirm hub gene expression from mucosal biopsy specimens.Results: There were a total of 142 genes co-upregulated and 65 genes co-downregulated. According to the WGCNA analysis, 42 genes were duplicated inside the light cyan module. GO and KEGG enrichment analyses of overlapped genes in nonresponders demonstrated an increase in the expression of genes associated with inflammation and immune response, consistent with GSEA results. The PPI network was constructed using 41 protein nodes and 177 edges. After validation, 8 of the top 10 genes were verified to be differentially expressed.Conclusion: Our investigation is the first to integrate three CD databases after the anti-TNF medication treatment. We identified IL1B, CCL4, CXCL1, CXCL10, CCL3, CSF3, TREM1, and IL1RN as potential therapeutic targets for patients whose anti-TNF treatment failed.Keywords: Crohn’s disease, weighted gene co-expression network analysis, robust rank aggreg, therapeutic targets

Lechang Yu,1 Ying Liu,2 Chao Cao,3 Liheng Yang,4 Haijing Liu,5 Chunli Wang5 1Department of Geriatrics, Tianjin Medical University General Hospital; Tianjin Geriatrics Institute, Tianjin, 300052, People’s Republic of China; 2Department of Integrated Traditional Chinese and Western Medicine, Tianjin First Central Hospital, Tianjin, 300192, People’s Republic of China; 3Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Tianjin Chest Hospital, Tianjin, 300222, People’s Republic of China; 5Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of ChinaCorrespondence: Haijing Liu; Chunli Wang, Department of General Surgery, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, People’s Republic of China, Tel +86-22-60363333, Email liuhaijing1980@163.com; charlywang2008@126.comPurpose: Intra-abdominal infection is a complex pathophysiological process involving multiple systems and organs of the body. Abdominal infections complicated by severe sepsis or septic shock have a high mortality rate of 30– 50%. Therefore, novel strategies to treat sepsis are urgently needed.Methods: Andrographolide (AD), the main active ingredient of Andrographis paniculata, reportedly exerts beneficial effects on mice with sepsis. However, its exact mechanism of action in attenuating inflammation due to intra-abdominal sepsis remains unclear to date. Hence, this study aimed to examine the therapeutic effects of AD on cecal ligation and puncture (CLP)-induced sepsis and elucidate the underlying mechanisms.Results: Results showed that AD therapy could significantly improve the 7-day survival rate and alleviate pathological organ injury in mice with CLP. In addition, AD treatment decreased the levels of proinflammatory factors, such as tumor necrosis factor-α and interleukin (IL)-6 in the peritoneal cavity fluid and blood and increased the level of anti-inflammatory factor IL-10 in the peritoneal cavity fluid of mice with CLP. Moreover, bacterial counts in the blood and peritoneal lavage fluid were lower in the mice treated with AD than in those untreated. Mechanistically, AD treatment increased the percentage and phagocytic activity of macrophages in the peritoneal cavity.Conclusion: These data showed that AD can improve the survival of mice with intra-abdominal sepsis by enhancing bacterial clearance, as evidenced by the increased percentages and phagocytic activity of macrophages in the peritoneal cavity. This study is the first to demonstrate the protective effects of AD against intra-abdominal sepsis.Plain Language Summary: Intra-abdominal infection is a complex pathophysiological process involving multiple systems and organs of the body. Abdominal infections complicated by severe sepsis or septic shock have a high mortality rate of 30– 50%. Therefore, novel strategies for treatment of sepsis are urgently needed. Andrographolide (AD), the main active ingredient of Andrographis paniculata, reportedly exerts beneficial effects on mice with sepsis. However, its exact mechanism of action in attenuating inflammation due to intra-abdominal sepsis remains unclear to date. Here, the study aimed to examine the therapeutic effects of AD on cecal ligation and puncture (CLP)-induced sepsis and elucidate the underlying mechanisms. Our findings showed that AD therapy could significantly improve the 7-day survival rate and alleviate pathological organ injury in mice with CLP. In addition, AD treatment decreased the levels of proinflammatory factors, such as tumor necrosis factor-α and interleukin (IL)-6 in the peritoneal cavity fluid and blood and increased the level of anti-inflammatory factor IL-10 in the peritoneal cavity fluid of mice with CLP. Moreover, bacterial counts in the blood and peritoneal lavage fluid were lower in the mice treated with AD than in those untreated. Mechanistically, AD treatment increased the percentage and phagocytic activity of macrophages in the peritoneal cavity. These data showed that AD can improve the survival of mice with intra-abdominal sepsis by enhancing bacterial clearance, as evidenced by the increased percentages and phagocytic activity of macrophages in the peritoneal cavity. This study is the first to demonstrate the protective effects of AD against intra-abdominal sepsis.Keywords: andrographolide, bacterial clearance, inflammatory response, 7-day survival rate, intra-abdominal sepsis

Ling Yang,1,2 Maolin Cao,3 Jing Tian,1 Peijin Cui,1 Ling Ai,3 Xue Li,4 Hua Li,5 Menghan Gao,1 Liang Fang,1,2,6 Libo Zhao,1,2 Fang Gong,2,6 Chanjuan Zhou1,3,4,6 1Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Cerebrovascular Disease Research, Chongqing, People’s Republic of China; 3Department of General Practice, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Central Laboratory, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 5Department of Ophthalmology, Yongchuan Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 6Chongqing Clinical Research Center for Geriatric Disease, Chongqing, People’s Republic of ChinaCorrespondence: Fang Gong; Chanjuan Zhou, Yongchuan Hospital of Chongqing Medical University, No. 439 Xuanhua Road, Yongchuan, Chongqing, 402160, People’s Republic of China, Email 1512367841@qq.com; chanjuanzhou@hospital.cqmu.edu.cnPurpose: The quality of life of worldwide adolescents has been seriously affected by depression. Notably, the inflammatory response is closely associated with the pathophysiology of depression. The present study applied a novel targeted proteomics technology, Olink proximity extension assay (PEA), to profile circulating immune-related proteins in adolescents with depression.Methods: In the present study, the expression levels of 92 inflammation-related proteins were compared between adolescents with depression (ADs) (n=15) and healthy controls (HCs) (n=15), using the OLINK PEA inflammation panel. We further validated 5 top proteins that were identified through KEGG and GO analyses between 40 HCs and 50 ADs, including CCL4, CXCL5, CXCL6, CXCL11, and IL-18 using enzyme linked immunosorbent assay (ELISA).Results: We identified 13 differentially expressed proteins between the two cohorts, including 5 up-regulated and 8 down-regulated proteins. Among them, the TRAIL protein levels were significantly negatively correlated with the HAMA-14 score (r=− 0.538, p= 0.038), and the levels of transforming growth factor α (TGF-α) were significantly associated with a change in appetite (r = -0.658, p = 0.008). After validation by ELISA, CCL4, CXCL5, CXCL11, and IL-18 showed significant changes between ADs and HCs (p < 0.05), while CXCL6 showed an up-regulated tendency in ADs (p=0.0673). The pooled diagnostic efficacy (area under the curve [AUC]) of these five inflammation markers in clinical diagnosis for adolescent depression was 0.819 (95% CI: 0.735– 0.904).Conclusion: We report a number of inflammation-related plasma biomarkers, which uncover a potential involvement of chemokines, cytokines, and cytokine receptors in adolescent depression. Their roles in the pathophysiology of depression need to be further elucidated.Keywords: olink proximity extension assay, biomarkers, adolescent depression, inflammation

Xiaolin Jin,1 Haiyan Sun,2 Lina Yang1,3 1Department of International Physical Examination Center, The First Hospital of China Medical University, Shengyang, People’s Republic of China; 2Department of Endodontics, School of Stomatology, China Medical University, Shenyang, People’s Republic of China; 3Department of Geriatrics, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Haiyan Sun; Lina Yang, Email 13066784163@163.com; yanglina1984@163.comAbstract: Sepsis is a systemic inflammatory reaction caused by infection. Severe sepsis can lead to multiple organ dysfunction, with a high incidence rate and mortality. The molecular pathogenesis of sepsis is complex and diverse. In recent years, with further study of the role of extracellular vesicles (EVs) in inflammatory diseases, it has been found that EVs play a dual role in the imbalance of inflammatory response in sepsis. Due to the great advantages such as lower toxicity, lower immunogenicity compared with stem cells and better circulation stability, EVs are increasingly used for the diagnosis and treatment of sepsis. The roles of EVs in the pathogenesis, diagnosis and treatment of sepsis were summarized to guide further clinical studies.Keywords: extracellular vesicles, sepsis, inflammatory response, exosome, microvesicle

Ling Wei,1,&ast; Qiyan Chen,2,3,&ast; Lu Yang,2,3 Tongzhen Ji,4 Wenjing Peng,5 Bing Shao,2 Hui Li2 1Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control, Beijing, People’s Republic of China; 3National Center for Veterinary Drug Safety Evaluation, College of Veterinary Medicine, China Agricultural University, Beijing, People’s Republic of China; 4Department of Clinical Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 5College of Animal Husbandry and Veterinary Medicine, Jinzhou Medical University, Jinzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Li; Bing Shao, Email lihui@bjcdc.org; shaobingch@sina.comObjective: The emerging epidemic of extended-spectrum β-lactamase-producing E. coli (ESBL-EC) is a global public health crisis. ESBL-EC infections are increasing worldwide and contribute to morbidity and mortality among newborn infants. However, the antimicrobial resistance characteristics and clonal transmission of maternal and neonatal ESBL-EC isolates need to be further deciphered.Materials and Methods: We performed phenotypic and genotypic characterization of 33 ESBL-EC isolates from pregnant women and newborn during 2019– 2020.Results: Minimum inhibitory concentrations of 17 antimicrobial agents showed that all isolates were multidrug-resistant (MDR) and had a resistance rate of 100% to ampicillin, and mild resistance to florfenicol, gentamicin, ceftazidime, and amoxicillin-clavulanate. Additionally, imipenem, meropenem, polymyxin, and tigecycline exhibited good activity against the tested ESBL-EC isolates with low MIC50 (0.06– 1 μg/mL) and MIC90 (0.06– 1 μg/mL). Whole genome sequencing indicated that ESBL-EC isolates contained diverse antimicrobial resistant genes (blaCTX-M, blaTEM, blaSHV, tetA, etc.) and toxin genes (ompA, csg, fimH, hybtA, etc.). blaCTX-M genes were the main ESBL genotype. ST1193 (18.2%) was the second most abundant ST among the ESBL-EC isolates (ST131 was the most common, with 30.3%), and this is the first report of its mother-to-infant colonization transmission in China.Conclusion: These findings revealed the occurrence of high-risk ST1193 clone among ESBL-EC isolates from pregnant women and newborn colonization in China. Further national or regional multicenter studies are needed to assess the dissemination and evolution of ESBL-EC ST1193 clone as a nosocomial pathogen in China.Keywords: ESBL, E. coli, antibiotic resistance, colonization transmission, ST1193 clone

Jiangli Ban,1,2 Xiaoyu Pan,2,3 Liqun Yang,2 Zhuoya Jia,2,3 Ruoxi Zhen,2,3 Xueqing Zhang,2,4 Shuchun Chen2,3 1Graduate School of Hebei North University, Zhangjiakou, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Graduate School of Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Graduate School of North China University of Science and Technology, Tangshan, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Endocrinology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, 050051, People’s Republic of China, Tel/Fax +86 31185988406, Email chenshuc2014@163.comPurpose: This study aimed to examine the correlation between fibrinogen/albumin (FAR) and diabetic peripheral neuropathy (DPN).Patients and Methods: A total of 342 patients were included and categorized into either the DPN group or the Non-DPN (NDPN) group based on their DPN status. The FAR index was determined by calculating the ratio of fibrinogen (FIB) to serum albumin (ALB), multiplied by 100. The participants were then divided into a High-FAR group and a Low-FAR group using the median FAR value as the threshold. Neurophysiological data were collected from the participants, which included motor conduction velocity (MCV) and sensory conduction velocity (SCV).Results: The DPN group displayed higher FAR levels [(DPN vs NDPN:6.72 (5.89,7.74) vs 5.94± 1.14], in addition to slower SCV and MCV data compared to the NDPN group. The high FAR group had a higher prevalence of DPN (78.9% vs 55.6%) (P< 0.05). There was a negative correlation between FAR and NCV, including bilateral median nerve SCV, left ulnar nerve SCV, bilateral median nerve MCV, bilateral common peroneal nerve MCV, bilateral tibial nerve MCV, and left ulnar nerve MCV. FAR was revealed to be an independent risk factor for the development of DPN in patients and demonstrated a greater predictive value for DPN development in Type 2 diabetes mellitus (T2DM) compared with FIB, HbA1c.Conclusion: The results suggest that monitoring FAR levels in patients with T2DM could identify those at higher risk for developing DPN, making the FAR index a valuable predictor of DPN development. Furthermore, since FAR has an inverse relationship with NCV, it stands to reason that high FAR levels may indicate nerve damage and slower conduction velocities. Thus, managing FAR could prove beneficial in both preventing and delaying the onset of DPN in T2DM patients.Keywords: type 2 diabetes mellitus, diabetic peripheral neuropathy, fibrinogen/albumin

Zitian Liang,1,&ast; Ding Chen,2,&ast; Ye Jiang,1 Zhikang Su,2 Yixing Pi,2 Tao Luo,2 Qianzhou Jiang,1 Li Yang,1 Lvhua Guo2 1Department of Endodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong, 510182, People’s Republic of China; 2Department of Prosthodontics, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong, 510182, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Yang; Lvhua Guo, Affiliated Stomatology Hospital of Guangzhou Medical University, No. 195 West Dongfeng Road, Guangzhou, 510182, People’s Republic of China, Tel +86-020-81299942, Email 2019686001@gzhmu.edu.cn; 2010686002@gzhmu.edu.cnIntroduction: Effective infection control without irritating the pulp tissue is the key to successful vital pulp therapy. Developing a novel antibacterial biomaterial that promotes dentin regeneration for pulp capping is thus a promising strategy for enhancing vital pulp therapy.Methods: Lithium-doped mesoporous nanoparticles (Li-MNPs) were synthesized using an alkali-catalyzed sol-gel method. The particle size, elemental distribution, surface morphology, pore structure, and ion release from Li-MNPs were measured. Human dental pulp stem cells (hDPSCs) and Streptococcus mutans (S. mutans) were used to evaluate the biological effects of Li-MNPs. In addition, a dental pulp exposure mouse model was used to evaluate the regenerative effects of Li-MNPs.Results: Li-MNPs had a larger surface area (221.18 m2/g), a larger pore volume (0.25 cm3/g), and a smaller particle size (520.92 ± 35.21 nm) than MNPs. The in vitro investigation demonstrated that Li-MNPs greatly enhanced the biomineralization and odontogenic differentiation of hDPSCs through the Wnt/β-catenin signaling pathway. Li-MNPs showed a strong antibacterial effect on S. mutans. As expected, Li-MNPs significantly promoted dentin regeneration in situ and in vivo.Conclusion: Li-MNPs promoted dentin regeneration and inhibited S. mutans growth, implying a possible application as a pulp capping agent in vital pulp therapy.Graphical Abstract: Keywords: lithium, mesoporous nanoparticles, dental pulp stem cells, dentin regeneration, Wnt/β-catenin signaling pathway, antibacterial properties

Xiaoqin Niu, Bolong Hou, Lunyun Yang, Wei Wang, Qinlong Yu, Minjie Mao, Weifeng Shen Department of Clinical Laboratory, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, Jiaxing, 314000, People’s Republic of ChinaCorrespondence: Weifeng Shen, Department of Clinical Laboratory, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, No. 1882, Zhonghuan South Road, Nanhu District, Jiaxing, Zhejiang, 314000, People’s Republic of China, Tel +86-18868345828, Email jyzhy526@163.comBackground: Urinary tract infections (UTIs) and the antibiotic resistance of pathogenic bacteria pose severe threats to public health in the current healthcare environment.Objective: The purpose of this study was to assess the frequency distribution of bacterial pathogens causing UTIs as well as the characteristics of antibiotic susceptibility and resistance.Methods: The retrospective study was conducted on 32,391 samples of midstream urine culture from January 1, 2020, to December 31, 2022, in Jiaxing. Bacteria were cultivated on blood agar and identified using MALDI-TOF, and their susceptibility to different antibiotics was assessed using the Kirby-Bauer disk diffusion method and drug sensitivity reaction cards. The SPSS 22 software was used for data analysis. Bivariate logistic regression was used to analyze the risk factors for multidrug resistance.Results: The total number of positive growth samples was 5378 (16.6%), including 3206 females (59.6%) and 2172 males (40.4%). The four most common urinary pathogens were Escherichia coli (39.2%), Enterococcus faecalis (12.4%), Klebsiella pneumoniae (7.6%), and Enterococcus faecium (7.6%). As far as antibiotic resistance was concerned, Escherichia coli had a greater than 50% resistance rate to ampicillin (76.1%), ciprofloxacin (58.6%), and levofloxacin (51.2%). The multidrug resistance rate was high (41.8%). Low levels of resistance were seen to ertapenem (0.1%), imipenem (0.7%), meropenem (0.7%), piperacillin/tazobactam (0.7%), and nitrofurantoin (1.8%). Klebsiella pneumoniae was highly sensitive to ertapenem (100%). The resistance rates to nitrofurantoin, ceftriaxone, and ciprofloxacin were 37.4%, 37.1%, and 35.1%, respectively. Up to 41% of Escherichia coli strains and 26% of Klebsiella pneumoniae strains produced extended-spectrum lactamases (ESBL). Two species of enterococci were highly sensitive to tigecycline and linezolid (100%), and a small number of norvancomycin-resistant strains (0.2%/two strains) were found.Conclusion: Escherichia coli and Enterococcus faecium were the most common urinary pathogens in this study. The isolated pathogens showed different sensitivity patterns. Antibiotics should be selected reasonably according to the sensitivity mode of pathogenic bacteria to effectively treat and prevent urinary tract infections.Keywords: antibiotic resistance, urinary tract infections, pathogenic bacteria, urine culture

Doudou Zheng,&ast; Liqin Yang,&ast; Meijuan Li, Yuying Qiu, Ying Gao, Jie Li Tianjin Mental Health Institute, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Li, Tianjin Mental Health Centre, Tianjin Anding Hospital, 13 Liulin Road, Hexi District, Tianjin, 300222, People’s Republic of China, Tel/Fax +86-22-88188006, Email jieli@tjmhc.comPurpose: Sex differences in depression have been well recognized. However, sex differences in depression among Omicron-infected individuals have received little systematic study. This study compared sex differences in depression in infected individuals during the 2022 Omicron pandemic in China.Patients and Methods: 506 individuals infected with Omicron (males/females = 268/238) were recruited from Tianjin and Shanghai in China. Self-developed Scale of Demographics were used to collect demographic and clinical data, Zung Self-Rating Depression Scale (SDS), Zung Self-Rating Anxiety Scale (SAS), the Connor-Davidson Resilience Scale (CD-RISC), De Jong Gierveld Scale (DJGLS), and the Penn State Worry Questionnaire (PSWQ) were used to measure respondents’ depression, anxiety, resilience, loneliness and worry, respectively.Results: The prevalence rate of depression in male patients was significantly higher than in female patients (42.2% versus 31.9%; χ2 = 5.64, p = 0.018). Regression analysis showed that in female patients, depression was associated with anxiety [OR = 1.26, 95% CI (1.16– 1.36), p < 0.001], and resilience [OR = 0.98, 95% CI (0.96– 1.00), p < 0.05], while in male patients, depression was associated with anxiety [OR = 1.24, 95% CI (1.15– 1.33), p < 0.001].Conclusion: This on-site study demonstrates that depression is more frequent in male than female Omicron-infected patients and suggests that sex differences should be considered in prevention and treatment strategies for depression during the Omicron pandemic.Keywords: depression, sex difference, Omicron-infected, China

Peng Chen,1 Juan Chen,2 Jinghe Ye,1 Limin Yang1 1Department of Urology, General Hospital of Northern Theater Command PLA, Shenyang, People’s Republic of China; 2Department of Oncology, General Hospital of Northern Theater Command PLA, Shenyang, People’s Republic of ChinaCorrespondence: Limin Yang, Department of Urology, General Hospital of Northern Theater Command PLA, No. 83, Wenhua Road, Shenhe District, Shenyang, 110000, People’s Republic of China, Tel/Fax +86-17790993188, Email yang__limin@163.comPurpose: Sepsis is an organ dysfunction with high mortality. Early identification, diagnosis, and effective treatment of sepsis are beneficial to the survival of patients. This study aimed to find potential diagnosis and immune-related genes, and drug targets, which could provide novel diagnostic and therapeutic markers for sepsis.Patients and Methods: The GSE69063, GSE154918 and GSE28750 datasets were integrated to evaluate immune infiltration and identify differentially expressed genes (DEGs) and immune-related genes. Weighted gene co-expression network analysis (WGCNA) was applied to find the hub module related to immune score and sepsis. Immune-related key genes were screened out by taking interaction of DEGs, immune-related genes, and genes in hub module. Protein–protein interaction (PPI) analysis was used to further screen immune-related hub genes, followed by construction of a diagnostic model based on immune-related hub genes. Functional analysis and drug prediction of immune-related hub genes were, respectively, performed by David software and DGIdb database, followed by expression validation by reverse transcriptase polymerase chain reaction (RT-PCR).Results: Totally, 93 immune-related key genes were identified between 561 DEGs, 1793 immune-related genes and 12,459 genes in the hub module of WGCNA. Through PPI analysis, a total of 5 diagnose and immune-related hub genes were further obtained, including IL7R, IL10, CD40LG, CD28 and LCN2. Relationship pairs between these 5 genes and immune cell were identified, including LCN2/IL7R/CD28-activated dendritic cell and IL10-immature B cell. Based on pharmacogenomics, 17 candidate drugs might interact with IL 10, including CYCLOSPORINE. Six candidate drugs might interact with CD28 and 11 with CD40LG, CD40LG and CD28 were drug targets of ALDESLEUKIN. Four significantly enriched signaling pathways were identified, such as T cell receptor signaling pathway, NF-kappa B signaling pathway and JAK-STAT signaling pathway.Conclusion: The 5-gene diagnostic model could be used to diagnose and guide clinical immunotherapy for sepsis.Keywords: sepsis, diagnosis, immune infiltration, drug target, WGCNA

Xin Yu,1,&ast; Lijun Xu,2,&ast; Yongqiang Zhou,3 Xiaorong Zhou,4 Lei Yang,2 Yan Zhou1 1Department of Orthodontics and Periodontology, Affiliated Nantong Stomatological Hospital of Nantong University, Nantong, People’s Republic of China; 2Department of Clinical Biobank & Institute of Oncology, Affiliated Hospital of Nantong University & Medical School of Nantong University, Nantong, People’s Republic of China; 3Department of Oral and Maxillofacial Surgery, Affiliated Nantong Stomatological Hospital of Nantong University, Nantong, People’s Republic of China; 4Department of Immunology, School of Medicine, Nantong University, Nantong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Zhou, Affiliated Nantong Stomatological Hospital of Nantong University, Nantong, 226001, People’s Republic of China, Tel +86 513-89898899, Fax +86 513-89898890, Email ntyaner@126.com Lei Yang, Affiliated Hospital of Nantong University & Medical School of Nantong University, Nantong, 226001, People’s Republic of China, Tel +86 513-85052806, Email yang-lei@ntu.edu.cnBackground: Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy with a high mortality rate and poor prognosis. The exploration and understanding of biomarkers will help to further improve the diagnosis and treatment of OSCC.Methods: Tumor tissue samples from 319 OSCC patients were retrospectively collected, along with their clinical information. In combination with bioinformatics tools and multiplex immunohistochemistry (mIHC) analyses, we evaluated NUP62CL protein expression and its relationship to tumor-infiltrating immune cells (TIICs) and immune checkpoints in the tumor microenvironment (TME), as well as its association with clinical features and prognosis of OSCC.Results: We identified high-NUP62CL expression in OSCC tissues, and high-NUP62CL protein expression was associated with large tumor size, advanced clinical stage and poor prognosis. In addition, NUP62CL protein expression was positively associated with the abundance of CD3+CD4+ T cells (P< 0.01), CD3+CD8+ T cells (P< 0.01), CD56+ NK cells (P< 0.05), CD68+CD86+ macrophages (P< 0.01) and CD68+CD163+ macrophages (P< 0.01), as well as the immune checkpoints, including PD-1 (P< 0.001), PD-L1 (P< 0.001), and CTLA-4 (P< 0.001) protein expression.Conclusion: In conclusion, NUP62CL could be an effective prognostic and immunological biomarker for OSCC patients.Keywords: oral squamous cell carcinoma, NUP62CL, mIHC, prognosis, tumor-infiltrating immune cells, biomarker

Shi Chen,1,&ast; Jiaqi Qiang,1,2,&ast; Bin Zhao,3 Ran Tian,4 Tao Yuan,1 Ming Li,1 Mei Li,1 Zhaoqi Gu,5 Liping Yang,6 Huijuan Zhu,1 Hui Pan,1,7 Yan Tang,3 Yuxiu Li1 1Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Eight-Year Program of Clinical Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 3Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 4Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 5Department of Radiotherapy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 6Department of Pharmacy, Handan First Hospital, Handan, Hebei Province, People’s Republic of China; 7State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuxiu Li, Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, People’s Republic of China, Email liyuxiu@medmail.com.cn Yan Tang, Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing, Dongcheng District, Beijing, 100730, People’s Republic of China, Email tangyan@pumch.cnAbstract: The sulfhydryl group of clopidogrel metabolite could induce insulin autoimmune syndrome (IAS) with hypoglycemia as the major symptom. For patients with cardiovascular disease taking clopidogrel for vascular protection, this adverse event hypoglycemia increases the risk of cardiovascular events. However, discontinuing clopidogrel leaves patients without appropriate antiplatelet therapy. Treating IAS with glucocorticoids is also risky for these patients’ primary cardiovascular diseases. Early recognition and appropriate treatment of clopidogrel-induced IAS (CIAS) would be beneficial for patients. This research aimed to discover the clinical features and investigate optimal therapeutic management of CIAS. We systematically searched for cases of CIAS in PubMed and Embase and performed data mining in Food and Drug Administration Adverse Event Reporting System (FAERS). In the CIAS series, clinical features were summarized and compared to 287 IAS cases, including demographic information, HLA alleles, onset, and symptoms. The therapeutic effect of glucocorticoids was compared between the receiving group and the not-receiving group. The possibilities of common antiplatelet drugs to induce hypoglycemia/IAS were investigated with chemical structure and FAERS reports. A CIAS series of 51 patients was established. CIAS had an onset age of 74.8± 8.6 years old, 92.2% male, and a balanced proportion of East Asians and non-East Asians. Confusion occurred more frequently in CIAS than in IAS from various causes, while the other symptoms and hypoglycemia types were similar. The recovery time was approximately the same whether using glucocorticoids/immunotherapy in CIAS or not. Among common antiplatelet drugs, ticagrelor and rivaroxaban were unlikely to induce hypoglycemia/IAS. Clopidogrel is a distinctive cause of IAS featuring an elderly male presenting confusion as the symptom of hypoglycemia. Glucocorticoids/immunotherapy might not be necessary for the long-term recovery of CIAS. To balance the risks of hypoglycemia and cardiovascular events, substituting clopidogrel with ticagrelor and rivaroxaban might be considered.Keywords: autoimmune hypoglycemia, antiplatelet therapy, glucocorticoids, cardiovascular diseases, ticagrelor

Zhirou Xiao,1,&ast; Liping Qu,2,&ast; Haijun Chen,1 Wanting Liu,2 Yi Zhan,2 Jiahui Ling,2 Hongwei Shen,3 Ling Yang,1 Dingqiang Chen2 1Department of Laboratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Clinical Laboratory, Shenzhen Hospital of Southern Medical University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Yang, Department of Laboratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, People’s Republic of China, Tel/Fax +86-20-83062158, Email jykresearch@126.com Dingqiang Chen, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, People’s Republic of China, Tel/Fax +86-20-62783335, Email jyksys@126.comBackground: Antibiotic resistance represents a serious global health challenge, particularly with the emergence of strains resistant to last-resort antibiotics such as tigecycline, polymyxin B, and vancomycin. Urgent measures are required to alleviate this situation. To facilitate the judicious use of antibiotics, rapid and precise antimicrobial susceptibility testing (AST) is essential. Heavy water (deuterium oxide, D2O)-labeled Raman spectroscopy has emerged as a promising time-saving tool for microbiological testing.Methods: Deuterium incorporation and experimental conditions were examined to develop and apply a Raman-based AST method to evaluate the efficacy of last-resort antibiotics, including tigecycline, polymyxin B, and vancomycin, against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus faecium. Essential agreement and categorical agreement were used to assess the metabolism inactivation concentration based on Raman spectroscopy (R-MIC)–a new metric developed in this study—and minimum inhibitory concentration (MIC) determined via the traditional microdilution broth method. Spearman’s rank correlation coefficient was employed to measure the association between R-MIC and MIC values.Results: The Raman-based AST method achieved a 100% categorical agreement (92/92) with the traditional microdilution broth method within five hours, while the traditional method required approximately 24 h. The R-MIC values shared 68.5% (63/92) consistency with the MIC values. In addition, the R-MIC and MIC values were highly correlated (Spearman’s r=0.96), resulting in an essential agreement of 100%.Conclusion: Our optimized experimental method and conditions indicate that Raman-based AST holds great promise as a solution to overcome the time-consuming challenges of traditional AST methods.Keywords: Raman spectroscopy, tigecycline resistant, polymyxin B resistant, vancomycin resistant, antimicrobial susceptibility testing

Shixiao Li,1 Peng Zhou,2 Lihong Yang,1 Tianbin Tang,1 Jiajia Qin,1 Jiao Qian,1 Shen Bo,1 Sufei Yu1 1Department of Clinical Microbiology Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, People’s Republic of China; 2Department of Pharmacy, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Sufei Yu, Email ysf5236791@163.comObjective: Severe pneumonia is a common infectious disease with high morbidity and mortality. Early etiological diagnosis is crucial for improving the prognosis. The aim of this study is to evaluate the clinical value of sampling time of mNGS in patients with severe pneumonia.Methods: This retrospective study enrolled 105 patients with severe pneumonia. mNGS was performed on bronchoalveolar lavage fluid (BALF). Patients were divided into the sampling time ≤ 72h vs sampling time > 72h groups and survivors vs non-survivors groups according to their sampling time and prognosis. Clinical characteristics, the adjustment of antibiotics and clinical prognostic value were evaluated.Results: Our study showed that, early sampling of mNGS can significantly shorten the mechanical ventilation time (p = 0.007) and hospitalization time (p = 0.004). In the non-survivors group, CURB-65, SOFA, and APACHE II scores were higher. Age (OR: 1.051, 95% CI: 1.004– 1.100, p = 0.034), chronic respiratory diseases (OR: 4.639, 95% CI: 1.260– 17.082, p = 0.021), immunosuppression (OR: 5.008, 95% CI: 1.617– 15.510, p = 0.005) and SOFA score on the day of mNGS sampling (OR: 1.492, 95% CI: 1.212– 1.837, p < 0.001) were independent risk factors of in-hospital mortality. The most common pathogens were Klebsiella pneumoniae and Human gammaherpesvirus 4. The proportion of appropriate and targeted antibiotics adjusted was significantly higher than that in the sampling time > 72h group, and the proportion of antifungal and antiviral agents adjusted was lower. In the early sampling group, it was significantly decreased in the CRP, PCT level and NEU% at discharge.Conclusion: This study demonstrated that early sampling of mNGS could shorten the time of mechanical ventilation and hospitalization of patients with severe pneumonia. Patients with higher SOFA score on the day of sampling had a poorer prognosis. It emphasizes that early sampling of mNGS has a positive value.Keywords: metagenomic next generation sequencing, severe pneumonia, sampling time, mortality