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Zijun Hu,1,* Lujian Zhu,2,* Yanglin Zhu,3 Yejin Xu2 1School of Medicine, Shaoxing University, Shaoxing, Zhejiang, People’s Republic of China; 2Department of Infectious Disease, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Gastrointestinal Surgery 2, Affiliated Jinhua Hospital of Wenzhou Medical University, Jinhua, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yejin Xu, Department of Infectious Disease, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, People’s Republic of China, Email xuyejin-fox@163.comAbstract: Lung diseases are associated with high morbidity and mortality rates, thereby jeopardizing human health and imposing a great burden on society. Currently, lung diseases are mainly treated with medications, oxygen therapy and mechanical ventilation, but these approaches are unable to effectively reduce the mortality rate. Therefore, lung transplantation remains the ultimate treatment for various chronic lung diseases, but this treatment is also hindered by the limited availability of lung sources, immature technology and a low survival rate after transplantation. With constant changes in the environment, pathogens, type and amount of harmful substances and the prevalence of respiratory diseases, there is an urgent need to identify alternative treatment methods. Research on stem cell therapy has been very successful in recent years, and mesenchymal stem cells (MSCs), together with their secretory bodies, play a significant therapeutic role. Extracellular vesicles of MSCs (MSC-EVs) are also major components of the paracrine secretion of MSCs, including exosomes, microvesicles, and apoptotic bodies, among which exosomes are the most typical. MSC-EVs are believed to be present in various tissues of the human body where they can carry proteins, DNA, RNA and biologically active factors, just to name a few. They can also transmit various biological signals to participate in different biological activities, including the maintenance of homeostasis within the tissue. Several studies have further demonstrated that MSCs and their generated extracellular vesicles play an important role in the treatment of diseases. In this paper, the origin, properties and roles of MSCs and MSC-EVs are reviewed, the mechanisms of different lung diseases, the limitations of current therapeutic options and the roles of MSC-EVs in Chronic Obstructive Pulmonary Disease, asthma, infectious lung disease, lung cancer, pulmonary fibrosis, pulmonary arterial hypertension, and acute lung injury/ acute respiratory distress syndrome are also discussed (Figure 1). In addition, the current limitations and possible future research directions are also discussed in view of providing new ideas for the role of MSC-EVs in the treatment of lung diseases.Keywords: mesenchymal stem cells, exosomes, lung disease, immunomodulation, epithelial mesenchymal transition (EMT), MSC-EVs

Zheng Li,1,2,&ast; Guang-Xin Duan,3,&ast; Jia-Hui Zhang,3 Yun Xu,3 Yun Luo3 1Department of Rehabilitation, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Rehabilitation, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 3Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Xu; Yun Luo, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China, Email xuyun208@163.com; luoyun@njglyy.comBackground: Chronic hypertension is an independent risk factor for ischemic stroke and worsens prognosis. However, the level of blood pressure control in hypertensive patients with severe intracranial stenosis is controversial.Purpose: To investigate the effect of different levels of blood pressure on cerebral perfusion in patients with middle cerebral artery severe stenosis or occlusion.Materials and methods: A total of 105 patients with isolated steno-occlusive middle cerebral artery (MCA) diagnosed by digital subtraction angiography (DSA) were enrolled, and PWI was compulsory. Relative risk factors were obtained by intergroup analysis in both hypertensive and non-hypertensive groups, and multivariable logistic regression was performed to determine whether hypertension was independently associated with PWI values. Next, the effects of different levels of blood pressure levels on cerebral perfusion as a whole and subgroup were further compared.Results: The hypertension (HT) group (Am 1.04± 0.05, Lm 1.07± 0.06, Pm 1.07± 0.05) demonstrated lower cerebral perfusion pressure at a larger rMTT (p=0.0001, 0.004, 0.006) than the nonhypertension (NHT) group (Am 1.01± 0.21, Lm 1.04± 0.04, Pm 1.04± 0.04). After adjustment for age, diabetes, and fibrinogen (FIB), HT was independently associated with the rMTT of Am, Lm, and Pm (P=0.015, 0.001, 0.022). Significant differences were observed with HT+SBP< 140 (p=0.035, 0.048, 0.049) and HT+DBP< 80 (p=0.034, 0.045, 0.055) in rMTT compared with NHT.Conclusion: Chronic hypertension might damage cerebral perfusion. Strictly control of blood pressure (< 140/80mmHg) in hypertensive patients with intracranial artery stenosis will further reduce ipsilateral cerebral perfusion.Keywords: blood pressure control, isolated severe steno-occlusive, PWI, cerebral perfusion

Lixin Xie,1,&ast; Lihua Feng,1,&ast; Xiaomin Tang,1 Yunping Xu,1 Hengyi Xu,2 Yang Liu1 1Department of Pediatrics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 2State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hengyi Xu, State Key Laboratory of Food Science and Resources, Nanchang University, 235 Nanjing East Road, Nanchang, 330047, People’s Republic of China, Tel +0086-791-8830-4447-ext-9520, Fax +0086-791-8830-4400, Email kidyxu@163.com; HengyiXu@ncu.edu.cn Yang Liu, Department of Pediatrics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1 minde Road, Nanchang, 330006, People’s Republic of China, Tel +86-791-8631-1209, Email ocean3166@yeah.netPurpose: To evaluate the therapeutic effect of oral administration of Lactiplantibacillus plantarum P101 (P101) on skeletal injury in young rats exposed to titanium dioxide nanoparticles (TiO2 NPs), and explore the potential mechanism.Methods: Four-week-old male rats were orally administration to TiO2 NPs and supplemented with P101 2 hours later for 4 weeks. The growth and development, food intake, bone metabolism and serum inflammatory markers of the rats were evaluated. Their tibias were observed and evaluated using microcomputed tomography (micro-CT), tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry (IHC) and real-time quantitative PCR (RT-qPCR). We observed the tibia growth plate using safranin and fast green staining. 16S rDNA sequence analysis of fecal samples was performed to observe changes in the gut microbiota.Results: Our results showed that TiO2 NPs can lead to bone growth inhibition and osteoporosis, induce intestinal flora imbalance, and induce inflammation in young rats. Further mechanistic studies suggested that TiO2 NPs disrupts intestinal flora and increases serum IL-1β levels, which increased the expression of RANKL in bone, thereby enhancing osteoclast differentiation and function, leading to bone loss. Through a P101 supplementation experiment, we found that P101 ameliorated the inflammation and osteoporosis on bone caused by TiO2 NPs.Conclusion: This study showed that the mechanism by which P101 alleviates bone damage caused by TiO2 NPs may be through restoring intestinal microbial homeostasis and inhibiting inflammatory response. Keywords: TiO2 NPs, P101, young rats, intestinal flora, bone injury, IL-1&#x03B2

Yang Xu,&ast; Qiankun Liu,&ast; Jiaxue Pang, Chunlu Zeng, Xiaoqing Ma, Pengyao Li, Li Ma, Juju Huang, Hui Xie College of Nursing, Bengbu Medical University, Bengbu, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Xie, Bengbu Medical University, Donghai Avenue, Longzihu District, Bengbu City, Anhui Province, People’s Republic of China, Email hui2122@sina.comPurpose: Exercise is a vital adjunct therapy for patients with hypertension comorbidities. However, medical personnel and patients face significant obstacles in implementing exercise prescription recommendations. AI has been developed as a beneficial tool in the healthcare field. The performance of intelligent tools such as ChatGPT 4.0 and Intelligent Health Promotion Systems (IHPS) in issuing exercise prescriptions for patients with hypertension comorbidities remains to be verified.Patients and Methods: After collecting patient information through IHPS hardware and questionnaire systems, the data were input into the software terminals of ChatGPT 4.0 and IHPS according to the five stages of the Transtheoretical Model, resulting in exercise prescriptions. Subsequently, experts from various fields scored the accuracy, comprehensiveness, and applicability of each prescription, along with providing professional recommendations based on their expertise. By comparing the performance of both systems, their capability to serve this specific group was evaluated.Results: In most cases, ChatGPT scored significantly higher than IHPS in terms of accuracy, comprehensiveness, and applicability. However, when patients exhibited certain functional movement disorders, GPT’s exercise prescriptions involved higher health risks, whereas the more conservative approach of IHPS was advantageous.Conclusion: The path of generating exercise prescriptions using artificial intelligence, whether via ChatGPT or IHPS, cannot achieve a completely satisfactory state.But can serve as a supplementary tool for professionals issuing exercise prescriptions to patients with hypertension comorbidities, especially in alleviating the financial burden of consulting costs. Future research could further explore the performance of AI in issuing exercise prescriptions, harmonize it with physiological indicators and phased feedback, and develop an interactive user experience.Keywords: artificial intelligence, exercise prescription, hypertension, intelligent health promotion systems, transtheoretical model

Na Zhang,1,&ast; Yiran Xu,1,2,&ast; Beibei Liang,1 Jinru Zeng,1 Rui Wang,1 Yun Cai1 1Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, PLA General Hospital, Beijing, People’s Republic of China; 2Department of Pharmacy, The Second Naval Hospital of Southern Theater Command of PLA, Sanya, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun Cai, Center of Medicine Clinical Research, Department of Pharmacy, Medical Supplies Center, PLA General Hospital, Beijing, People’s Republic of China, Tel +86-10-6693-7166, Email caicai_hh@126.comAbstract: Colistin is the last-line option for the treatment of multidrug-resistant gram-negative bacterial infections with narrow therapeutic window. It is essential to ensure its efficacy and safety by therapeutic drug monitoring (TDM). Quantitative determination of colistin is difficult due to its complex ingredients. Previous determination methods demand intricate sample pre-treatment which are not only time-consuming but also costly, and is difficult to apply in clinical practice. Therefore, in order to carry out quantitative determination of colistin accurately and quickly, we establish a rapid high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) with simple sample pre-treatment process. The sample was purified by acetonitrile to remove the plasma protein. Then purified colistin was effectively separated from terfenadine, an internal standard (IS) using Phenomenex Kinetex C18 column (50.0× 2.1mm, 5μm) with acetonitrile and water mobile phase at a flow rate of 0.5 mL/min and 40°C column temperature. Colistin and IS were monitored in positive ion mode. Our method expressed good linearity in 50.0~6000 ng/mL of colistin B and 28.31~3397.51 ng/mL of colistin A in plasma. Methodology validations, including selectivity, precision, accuracy, recovery, stability, matrix effect, and dilution integrity met acceptance criteria of Bioanalytical Method Validation (M10) of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).Keywords: colistin, HPLC-MS/MS, human plasma, protein precipitation, rapid and simple detection

Zhiyuan You,1 Jialin Zhang,1 Yifeng Xu,1 Junhong Lu,1 Renling Zhang,2 Zhujing Zhu,3 Yiqin Wang,1 Yiming Hao1 1Shanghai Key Laboratory of Health Identification and Assessment/Laboratory of TCM Four Diagnostic Information, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Gastroenterology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3Rheumatology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Yiming Hao, Email hymjj888@163.comObjective: This study aimed to establish a model for identifying chronic gastritis with the traditional Chinese medicine damp phlegm pattern by examining metabolite changes in the tongue coating of patients. It also explored the role of metabolic pathways in the pathogenesis of this condition.Methods: This cross-sectional study involved 300 patients diagnosed with chronic gastritis. Of these, 200 patients exhibited the damp phlegm pattern, while 100 did not. Metabolomic methods employing GC-TOF-MS and UHPLC-QE-MS were utilized to identify various metabolites in the tongue coating of patients. An identification model for chronic gastritis with the damp phlegm pattern was created based on ROC curves derived from differential biomarkers. Additionally, 50 samples not included in model construction were collected for external validation.Results: Comparison of the damp phlegm pattern group with the non-damp phlegm pattern group revealed a total of 116 differential metabolites. Among these, lipids and lipid-like compounds were most abundant, comprising 27 types, which included four lipid metabolites related to sphingomyelin metabolism. The ROC model, which included phenol, 2.6-diaminoheptanedioic acid, and N-hexadecanoyl pyrrolidine, demonstrated the highest accuracy, with accuracy, sensitivity, and specificity metrics of 94.0%, 91.0%, and 87.0%, respectively. Furthermore, external validation using tongue coating metabolites from 50 patients revealed accuracy, sensitivity, and specificity in the validation set of 93.9%, 90.6%, and 83.3%, respectively.Conclusion: Differential metabolites between patients with the damp phlegm pattern and those without are primarily lipids and lipid-like compounds. N-hexadecanoyl pyrrolidine, phenol, and 2.6-diaminoheptanedioic acid may serve as potential biomarkers for chronic gastritis characterized by the damp phlegm pattern.Keywords: chronic gastritis, damp phlegm pattern, tongue coating, metabolomics, biomarkers

Guiyun Zhang,1 Zhe Liu,1 Zhen Li,2 Yangchun Xu1 1Department of Dermatology, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China; 2Department of Medical Administration, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of ChinaCorrespondence: Yangchun Xu, Department of Dermatology, The Second Hospital of Jilin University, No. 218 Ziqiang Street, Nanguan District, Changchun, 130041, People’s Republic of China, Tel +86-431-81136244, Email Xuyc@jlu.edu.cnAbstract: Keloids are pathologic scars that pose a significant functional and cosmetic burden. While the literature on keloid management continues to expand, the absence of standardized guidelines or treatment protocols endorsed by academic governing bodies remains a significant challenge. The pathogenesis of keloid scars is not fully elucidated. This review delves into the intricate pathogenesis of keloids, exploring the molecular and cellular mechanisms underlying their formation. Conventional therapies are analyzed in-depth considering their efficacy and limitations, including surgical excision, pharmacotherapies, radiotherapy, cryotherapy, silicone-based product, pressure therapy, and light-based therapy. The emergence of novel therapeutic approaches is discussed, including pharmacotherapies, physical therapies, and biological therapies, shedding light on their potential in treating keloid scars. We also contemplate future directions in the field, encompassing the application of targeted therapies, gene-editing tools, tissue engineering, and regenerative medicine, together with psychosocial support and patient education. In synthesizing current knowledge, scrutinizing therapeutic modalities, and envisioning future avenues, this review aims to provide a comprehensive reference for clinicians, researchers, and stakeholders engaged in the intricate field of keloid management.Keywords: keloid scars, pathogenesis, therapies

Chenhao Suo,1,&ast; Yiru Gao,2,&ast; Sheng Yang,2 Wanli Zhang,2 Chao Li,3 Lanjing Ma,2 Yingchun Xu,4,5 Jianjun Lei,1 Chen Ding,2 Hailong Li,6 He Zhang,1 Tianshu Sun4,7 1Laboratory Animal Department, Northern Theater General Hospital, Shenyang, Liaoning, 110000, People’s Republic of China; 2College of Life and Health Science, Northeastern University, Shenyang, Liaoning, 110000, People’s Republic of China; 3Department of Emergency Medicine, the Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China; 4Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Beijing, 100730, People’s Republic of China; 5Medical Research Centre, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, 100730, People’s Republic of China; 6Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, 48109, USA; 7Clinical Biobank, Medical Research Center, National Science and Technology Key Infrastructure on Translational Medicine, 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: Tianshu Sun; He Zhang, Email sun_tianshu@163.com; alwayszhh@163.comIntroduction: The role of endocytosis in Candida albicans drug-resistance and pathogenicity remains poorly understood, despite its importance as a fundamental component of intracellular trafficking.Objective: In order to understand the role of endocytosis in Candida albicans cell wall integrity, drug resistance, and virulence.Methods: Detection of intracellular endocytosis by FM4-64 staining; Scanning electron microscopy is used to detect cell wall components; Spot assay for detecting drug sensitivity; Co-ip is used to detect protein interactions.Results: In this study, we found the functions of Sla1 in regulating endocytosis is conserved among pathogenic fungi. Our results also revealed that the deletion of the SLA1 gene altered cell wall properties, composition, and gene expression. In addition, we showed that C. albicans Sla1 was responsible for hyphal development in vitro and for fungal pathogenicity in a murine infection model. Intriguingly, sla1∆/∆ mutant demonstrated enhanced drug resistance, and Sla1 was found to interact with the transcription factor Efg1; the relationship between Sla1 and Efg1 impacts the expression of genes encoding components of the ergosterol biosynthesis pathway, including ERG1, EGR11, and ERG25.Discussion: These findings have expanded our knowledge of the capabilities of Sla1 beyond its role as an endocytosis adapter and provided insights into a potential new therapeutic target for the treatment of fungal infections.Keywords: endocytosis, Sla1, cell wall integrity, drug susceptibility, fungal pathogenicity

Linjun Tang, Yong Xu, Liangwei Wang, Jingjing Pan, Yong Wu Department of Neurosurgery, The Second People’s Hospital of Wuhu, Wuhu, People’s Republic of ChinaCorrespondence: Yong Wu, Department of Neurosurgery, The Second People’s Hospital of Wuhu, 6 Du Chun Road, Wuhu, Anhui, 241000, People’s Republic of China, Tel +86-17775461605, Email wuyong760617@163.comBackground: This study explores risk determinants for participants’ lower extremities deep vein thrombosis (DVT) in the perioperative phase after spontaneous intracerebral hemorrhage (SICH), thereby informing more effective clinical prevention and treatment strategies.Methods: During the period spanning October 2021 to March 2024, clinical data from 96 participants who received surgical treatment for spontaneous cerebral hemorrhage was analyzed in a retrospective study. Participants were classified into DVT and negative-DVT groups within the first week post-surgery. We used univariate logistic regression and multivariate logistic regression analyses to assess the impact of various clinical variables on DVT. A nomogram model was constructed to forecast the occurrence of early DVT following SICH surgery. The model’s performance was assessed and validated using receiver operating characteristic (ROC) curves and bootstrap resampling.Results: Among the 96 participants, 46 developed DVT. Significant differences were noted in age, D-dimer levels, fibrinogen degradation products, Caprini scores, and total surgical bleeding volume between the groups. Multivariate analysis revealed that Caprini score (the values of OR, 95% CI, and P are 1.962, 1.124– 3.424, and 0.018, respectively) and total surgical bleeding volume (the values of OR, 95% CI, and P are 1.010, 1.002– 1.018, and 0.017, respectively) were risk variables contributing to DVT occurrence. The area under the receiver operating characteristic curve was 0.918 (95% CI, 0.821– 0.988). The calibration curve showed good prediction accuracy.Conclusion: The Caprini score and total surgical bleeding volume are meaningful self-reliant risk variables contributing to DVT occurrence in postoperative participants with SICH. We have created a straightforward and efficient model to predict early DVT post-SICH surgery. This model serves as a valuable clinical tool for evaluating individual risk and enhancing decision-making processes.Keywords: spontaneous intracerebral hemorrhage, perioperative postoperative period, lower extremities deep vein thrombosis, caprini score, total surgical bleeding volume

Ciyi Hua,1 Feifei Li,1 Youyang Shi,2 Yuan Xu,1 Mengdie Zhu,1 Yang Wang,1 Xiqiu Zhou,2 Sheng Liu1,3 1Institute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Breast Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Sheng Liu, Institute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China, Tel +86 18917763005, Fax +86-64385700, Email shengliu@shutcm.edu.cnBackground: Patients with clinically cured granulomatous lobular mastitis (GLM) still face a high probability of recurrence and new occurrence.Purpose: To evaluate the long-term efficacy of traditional Chinese medicine (TCM) in treating GLM and to hypothesize potential risk factors for recurrence or new occurrence.Patients and Methods: A retrospective analysis was conducted on GLM patients treated with TCM at Longhua Hospital affiliated with Shanghai University of Traditional Chinese Medicine from January 2016 to July 2021. We analyzed general data, two-year recurrence and new occurrence rates, and 12 risk factors associated with recurrence or new occurrence.Results: This cross-sectional study included 261 GLM patients with an average age at onset of 31.95 years (primarily aged 31– 40). The two-year recurrence rate for GLM was 1.53%, and the new occurrence rate was 4.21%. Univariate and multivariate conditional logistic regression analyses revealed that a history of inverted nipples was associated with the risk of both recurrence and new occurrence of GLM (HR = 8.672, 5.375, P < 0.05), and menstrual irregularity was related to a higher risk of recurrence (HR = 13.172, P < 0.001).Conclusion: A history of inverted nipples is identified as a potential risk factor associated with the long-term recurrence and new occurrence of GLM, while menstrual irregularity is associated with recurrence. Despite this, patients with GLM undergoing TCM demonstrate low rates of long-term recurrence and new occurrence after achieving clinical cure, underscoring the effectiveness of TCM. This study lays the groundwork for a long-term effectiveness strategy to guide future GLM treatments.Keywords: granulomatous lobular mastitis, GLM, recurrence, new occurrence, risk factor

Jun Song,1 Ning Li,1 Ruihua Li,1 Yuanyuan Xu2 1Department of Pediatrics, Taihe County People’s Hospital, Fuyang, Anhui, 236000, People’s Republic of China; 2Pediatric Intensive Care Unit, Anhui Children’s Hospital, Hefei, Anhui, 230051, People’s Republic of ChinaCorrespondence: Yuanyuan Xu, Pediat Intens Care Unit, Anhui Children’s Hospital, 39 Wangjiang East Road, Baohe District, Hefei, Anhui, 230051, People’s Republic of China, Tel +86-551-62237451, Email Xuyuanyuan7451@163.comObjective: This study aimed to probe the changes in coagulation function-related indicators (prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-dimer (D-D), and fibrinogen degradation product (FDP)) in severe pneumonia and their clinical significance.Methods: The levels of coagulation function indicators of all the children were measured within 24 hours of admission. Pearson correlation analysis was utilized to analyze the correlation between PT, APTT, FIB, D-D, FDP and PCIS in children with severe pneumonia. The ROC curve was drawn to assess the power of PT, APTT, FIB, D-D and FDP in diagnosing severe pneumonia and predicting the prognosis of severe pneumonia. A logistic regression analysis was implemented to analyze the factors influencing the prognosis of children with severe pneumonia.Results: PT, APTT, FIB, FDP, and D-D in the critically severe pneumonia and the extremely severe pneumonia groups were higher versus the common pneumonia group (P < 0.05). FDP and D-D levels in children with severe pneumonia were negatively correlated with PCIS. PT, APTT, FIB, FDP, and D-D of children in the poor prognosis group were higher compared with those in the good prognosis group (P < 0.05). Further logistic regression analysis unveiled that FDP and APTT were influential factors impacting the prognosis of severe pneumonia.Conclusion: The levels of D-D, FDP, FIB, APTT, and PT in severe pneumonia are increased. Detecting the contents of coagulation function indicators can help clinical judgment of the changes in the condition of severe pneumonia and evaluate prognosis.Keywords: severe pneumonia, prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer, fibrinogen degradation product, pediatric critical illness score

Fang Yang, Yuedan Xu, Xiangyu Li Department of Pharmacy, Shaoxing Keqiao Women & Children΄s Hospital, Shaoxing, Zhejiang, People’s Republic of ChinaCorrespondence: Xiangyu Li, Department of Pharmacy, Shaoxing Keqiao Women & Children΄s Hospital, Shaoxing, Zhejiang, 312030, People’s Republic of China, Tel +86-0575-85028228, Email 1070817321@qq.comAbstract: Severe drug eruption is a severe allergic reaction to a drug, usually due to irritation with certain drugs. It may be present as a generalized erythematous maculopapular rash, a pleomorphic rash, with or without blisters and ulcers. To the best of our knowledgeto date, there is no report of estradiol valerate-induced severe drug eruption. A case of rare severe drug eruption after taking estradiol valerate tablets was first reported to promote clinical drug safety management, especially for rare severe adverse reactions. Meanwhile, it is speculated that estrogen dermatitis might be associated with dendritic cell-mediated allergic mechanisms, inflammation-induced expression of estrogen receptor β, and elevated estrogen levels during pregnancy, according to previous studies. Therefore, pregnant women using this drug need to be focused on. Early and systemic use of glucocorticoids is beneficial to the outcome and prognosis of the disease. It highlights the need for clinicians to be vigilant about rare but serious adverse drug reactions, even with medications that are generally considered safe.Keywords: severe drug eruption, estrogen dermatitis, estradiol valerate, adverse drug reaction, pharmacovigilance

Linsheng Wang,1,&ast; Yang Xu,2,&ast; Xudong Zhang,1 Jiahui Ding,1 Jingkun Jin,1 Jing Zong,1 Fangfang Li,1 Weidong Qian,3 Wenhua Li1,4 1Institute of Cardiovascular Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Cardiology, Xuzhou Central Hospital, Xuzhou, Jiangsu, People’s Republic of China; 3Department of Cardiology, Wujin Affiliated Hospital of Nanjing University of Chinese Medicine, Changzhou, Jiangsu, People’s Republic of China; 4Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weidong Qian, Department of Cardiology, Wujin Affiliated Hospital of Nanjing University of Chinese Medicine, Changzhou, Jiangsu, People’s Republic of China, Email qwd213161@163.com Wenhua Li, Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China, Email xzwenhua0202@163.comBackground: Contrast-induced acute kidney injury (CI-AKI) refers to the acute renal dysfunction caused by the injection of contrast agents. CI-AKI is currently a common complication after percutaneous coronary intervention (PCI).Objective: To investigate the predictive value of the combined systemic inflammatory index (SII) and urate/high-density lipoprotein cholesterol ratio (UHR) for CI-AKI after PCI in patients with AMI.Methods: A total of 1222 patients with AMI who underwent PCI were randomly divided into a training group and a validation group in an 8:2 ratio. According to the definition of CI-AKI diagnostic criteria, the training group was divided into CI-AKI group and non-CI-AKI group. Collect patient’s blood and biochemical data, then calculate SII and UHR. The risk factors for CI-AKI were identified using LASSO and multivariate logistic regression analyses. A predictive column was created by using R language.Evaluate the predictive value of SII, UHR and their combination for CI-AKI after PCI using the area under the ROC curve (AUC).Results: Diabetes, Cystatin C, Diuretics, UHR, and LnSII were independent risk factors for CI-AKI in AMI patients after PCI. The ROC curve showed that the AUC of UHR and SII combined for predicting CI-AKI in AMI patients after PCI was 0.761 (95% CI: 0.709– 0.812), with a sensitivity of 65.20% and a specificity of 76.70%, which was better than the prediction by either factor alone.Conclusion: High SII and high UHR are risk factors for AMI, and their combination can improve the accuracy of predicting CI-AKI in AMI patients after PCI.The prognosis of CI-AKI in AMI patients is worse than in the general population.Keywords: serum uric acid, high-density lipoprotein cholesterol, neutrophils, lymphocytes, systemic immune-inflammatory index, contrast-induced acute kidney injury

Yichen Wang,1,&ast; Yibo Zhang,1,&ast; Qun Wang,1 Wenhui Li,1 Dake Shi,1 Yumin Xu1,2 1Department of Hospital Infection Management, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yumin Xu, Email xym121@163.comPurpose: Hospital-acquired infections (HAIs) caused by multidrug-resistant organisms (MDROs) pose a significant challenge to healthcare systems. The present study aimed to evaluate the impact of the infection policy to COVID-19 on the incidence of HAIs caused by MDROs.Methods: We conducted an eight-years retrospective analysis at a hospital in Shanghai, China. Bloodstream, sputum, and urinary tract cultures of MDROs obtained 48h after admission were collected monthly from January 2016 to Dec 2023. Occupied bed days (OBDs) were used to generate monthly HAI incidences per 10,000 OBDs. The study period was divided into pre-control, in-control, and post-control cohorts, in January 2020 and January 2022. The incidence was compared using interrupted time-series regression.Results: In total, 6763 MDRO cultures were identified, comprising 1058 bloodstream, 4581 sputum, and 1124 urine cultures derived from 4549 patients. The incidence rates of all HAIs were 8.68 per 10,000 OBDs in the pre-control cohort, 9.76 per 10,000 OBDs in the in-control cohort and 12.58 per 10,000 OBDs in the post-control cohorts, respectively. A downward trend in the incidence of HAI was observed in the post-control cohort (p< 0.05).Conclusion: This study demonstrates that while the COVID-19 pandemic poses a significant challenge to infection control within hospitals, it provides a unique opportunity to enhance infection control measures and evaluate their effectiveness. In addition, these findings highlight the need for more targeted prevention and control strategies against different pathogens in future epidemics.Keywords: hospital required infection, multidrug-resistant organism, infection control, policy, Covid-19, surveillance

Yang Xu,1,&ast; Yue Wu,1,&ast; Jianhong Liu,2 Lili Xiao,1 Ying Zhang1 1Department of Gastroenterology, Daqing Oilfield General Hospital, Daqing, Heilongjiang, 163000, People’s Republic of China; 2Department of Breast and Thyroid Surgery, Daqing Oilfield General Hospital, Daqing, Heilongjiang, 163000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Zhang, Email zhangying750114@163.comBackground: The study explored the prognostic value of caudal-type homeobox transcription factor 2 (CDX2) in stage II and III gastric cancer.Methods: This study evaluated the expression level of CDX2 in gastric cancer in a hospital cohort (n=197) using immunohistochemistry. According to a semiquantitative score used to determine CDX2 expression, the cases were divided into a low CDX2 group (116 cases) and a high CDX2 group (81 cases). The RNA-seq expression data from 291 patients with stage II and III gastric cancer from The Cancer Genome Atlas (TCGA) cohort were used to verify the immunohistochemistry results. Based on the median CDX2 expression value, the TCGA patients were divided into a low CDX2 group (145 cases) and a high CDX2 group (146 cases). The relationships among CDX2 expression and clinicopathological features were determined using the Chi-square test. Cox proportional hazards regression models were applied to estimate the independent prognostic factors. The probability of survival was determined using the Kaplan-Meier method and Log rank tests.Results: Based on the Cox multivariate analysis, CDX2 was the independent prognostic factor in the hospital and TCGA cohorts. In the hospital cohort, CDX2 expression was associated with an improved DFS (hazard ratio [HR] = 0.4076, 95% CI, 0.2675– 0.6210, P = 0.0001) and OS (HR = 0.4183, 95% CI, 0.2744– 0.6375, P = 0.0002). In the TCGA cohort, CDX2 expression also was associated with an improved DFS (HR = 0.5948, 95% CI, 0.4153– 0.8521, P = 0.0054) and OS (HR = 0.5976, 95% CI, 0.4172– 0.8561, P = 0.0058). Furthermore, the CDX2 expression level was correlated with an improved DFS (P = 0.0025) and OS (P = 0.0015) using the Kaplan-Meier Plotter database for gastric cancer.Conclusion: CDX2 is a potential prognostic biomarker for stage II and III gastric cancer. In addition, CDX2 positive cancer patients are more likely to have resectable tumors and exhibit better survival rates.Keywords: gastric cancer, CDX2, immunoreactivity, chemotherapy, prognostic marker

Xin Guo,1,&ast; Ying Xu,1,&ast; Yao Meng,1,2,&ast; Hao Lian,1,&ast; Jingwen He,1 Ruike Zhang,1 Jingzhou Xu,1 Hao Wang,1 Shuyu Xu,1 Wenpeng Cai,1 Lei Xiao,1 Tong Su,3 Yunxiang Tang3 1Department of Medical Psychology, Faculty of Psychology, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Diving and Hyperbaric Medical Research, Naval Special Medical Center, Naval Medical University, Shanghai, People’s Republic of China; 3Faculty of Psychology, Naval Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunxiang Tang, Email tangyun7633@sina.comBackground: Napping deprivation in habitual nappers leads to cognitive impairment. The ameliorative effect of acute aerobic exercise has been demonstrated for this post-cognitive impairment. However, it is still unclear which intensity of aerobic exercise is the most effective and how long this improvement can be sustained.Methods: Fifty-eight healthy adults with a chronic napping habit were randomly assigned to four intervention groups after undergoing nap deprivation: a sedentary control group, a low-intensity exercise group (50– 59% maximum heart rate, HRmax), a moderate-intensity exercise group (60– 69% HRmax), and a high-intensity exercise group (70– 79% HRmax). Working memory (N-back task), vigilance (Psychomotor Vigilance Task, PVT), and response inhibitory capacity (Go/NoGo task) were measured.Results: Regression analyses showed a quadratic trend between exercise intensity and working memory reaction time and accuracy (F =3.297– 5.769, p < 0.05, R2 =10.7– 18.9%). The effects of exercise were optimal at low-intensity. There was a significant quadratic trend between exercise intensity and PVT lapse (F =4.314, p =0.042, R² =7.2%). The effect of exercise increased with higher intensity. Prolonged observation found that the effect of low-intensity exercise on working memory was maintained for 2 hours.Conclusion: The effect of low-intensity exercise might be underestimated. Low-intensity exercise significantly improved working memory performance, and the effects could be maintained throughout the afternoon. In contrast, the effects of high-intensity exercise were unlikely to be maintained and might even have negative effects. Future researchers can broaden the categories of participants to enhance the external validity and collect diverse physiological indicators to explore related physiological mechanisms.Keywords: exercise intensity, executive function, habitual nappers, nap deprivation, working memory

Jia Wei,1,&ast; Mingfen Song,1,&ast; Hong Jing Mao,1 Ruobing Qi,1 Lili Yang,1 You Xu,1 Pan Yan,1 Linlin Hu2 1Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310013, People’s Republic of China; 2Sleep Medicine Center, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310013, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Jing Mao, Email maohongjing@hz7hospital.comBackground: The effectiveness of medication combined with smartphone-delivered cognitive behavioral therapy for insomnia (CBT-I) has been well verified, but there are few studies on the sequence of remission of insomnia symptoms. This study aims to understand the sequence of symptom improvement and the factors influencing the treatment effectiveness in patients with insomnia.Methods: Smartphone-delivered CBT, as a form of Online CBT, allows for training through mobile devices at any time and place. We utilized the Good Sleep 365 app to conduct a survey, involving 2820 patients who met the baseline inclusion criteria. These patients were assessed using a general demographic questionnaire and the Pittsburgh Sleep Quality Index (PSQI) to evaluate general demographic information and insomnia symptoms, and subsequently underwent CBT training using the Good Sleep 365 app. A total of 1179 patients completed follow-ups at 4 weeks, 8 weeks, 16 weeks, and 24 weeks.Results: At 4 weeks and 8 weeks, the descending order of the reduction rates of PSQI components (excluding component 6: use of sleeping medication) was: sleep latency, subjective sleep quality, sleep efficiency, sleep disturbance, sleep maintenance, and daytime dysfunction. At 16 weeks and 24 weeks, the descending order was subjective sleep quality, sleep latency, sleep efficiency, daytime dysfunction, sleep maintenance, and sleep disturbance. There were significant differences in the reduction rates of PSQI components (excluding component 6: use of sleeping medication) both at the same follow-up times and at different follow-up times (all P< 0.05). Multivariable logistic regression analysis showed that patients older than 30 years and those with a college degree or above had better treatment outcomes, whereas those with a disease duration of more than three years had worse outcomes.Conclusion: The sequence of symptom improvement in patients with insomnia changes over time, and age, educational level, and duration of disease are factors influencing treatment outcomes.Keywords: insomnia, CBT-I, PSQI, influencing factors

Xiaojuan Gao,&ast; Tiansheng Bu,&ast; Wenying Wang, Ying Xu Department of Traditional Chinese Medicine, The Third Affiliated Hospital of Gansu University of Chinese Medicine, Baiyin, Gansu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Xu, Department of Traditional Chinese Medicine Management, The Third Affiliated Hospital of Gansu University of Chinese Medicine, Baiyin, Gansu, People’s Republic of China, Email 18009432685@163.comAbstract: Breast cancer remains the most prevalent malignancy among women globally, presenting significant challenges in therapeutic strategies due to tumor heterogeneity, drug resistance, and adverse side effects. Recent advances in targeted therapies, particularly antibody-drug conjugates (ADCs), have shown promise in addressing these challenges by selectively targeting tumor cells while sparing normal tissues. This study provides a comprehensive analysis of two innovative ADCs targeting HER2 and Trop-2, which are critical markers in various breast cancer subtypes. These conjugates combine potent cytotoxic drugs with specific antibodies, leveraging the antigens’ differential expression to enhance therapeutic efficacy and reduce systemic toxicity. Our comparative analysis highlights the clinical applications, efficacy, and safety profiles of these ADCs, drawing on data from recent clinical trials. In addition, the paper discusses the potential of these ADCs in treating other types of cancers where HER2 and Trop-2 are expressed, as well as the toxicity risks associated with targeting these antigens in normal cells. Additionally, the paper discusses novel synthetic drugs that show potential in preclinical models, focusing on their mechanisms of action and therapeutic advantages over traditional chemotherapy. The findings underscore the transformative impact of targeted ADCs in breast cancer treatment, noting significant advancements in patient outcomes and management of side effects. However, ongoing issues such as resistance mechanisms and long-term safety remain challenges. The conclusion offers a forward-looking perspective on potential improvements and the future trajectory of ADC research. This study not only elucidates the current landscape of ADCs in breast cancer but also sets the stage for the next generation of oncological therapeutics. This study not only elucidates the current landscape of ADCs in breast cancer but also sets the stage for the next generation of oncological therapeutics, with particular attention to their broader applications and associated risks.Keywords: breast cancer, antibody drugs, HER2, Trop-2

Qiaolin Zhang,1,&ast; Zhu Mei,2,&ast; Lan Wei,1 Dong Liu,1 Chengbing Xie,1 Yongzhu Xu1 1Department of Clinical Laboratory, Chongqing Blood Center, Chongqing, People’s Republic of China; 2Department of Clinical Laboratory, The First People’s Hospital of Chongqing Liangjiang New Area, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongzhu Xu, Department of Clinical Laboratory, Chongqing Blood Center, Chongqing, People’s Republic of China, Email xucqbc123@126.comObjective: Hepatitis B virus (HBV) infection is a significant global public health concern, with variable prevalence rates across regions. The prevalence of transfusion-transmitted HBV infection (TT-HBV) via donated blood necessitates an evaluation of blood safety and potential risks to the population. This study assessed the prevalence of HBV infection among blood donors in Southwestern China over 6 years.Methods: We analyzed 903,023 blood donations from a central blood center in Southwestern China between January 2017 and December 2022. The prevalence of HBV in donations was determined for one-time and repeat donors, considering birth cohorts and covariates. Demographic characteristics, donation frequency, and anti-HBV antibody status were analyzed to estimate the incidence of TT-HBV.Results: One-time donors provided 47.78% of the samples, and 52.22% were from repeat donors. The HBV prevalence decreased from 1.0% in 2017 to 0.87% in 2022 in one-time donors and from 0.30% to 0.09%, respectively, in repeat donors. A significantly lower HBV prevalence was identified in the post-1992 birth cohort (0.33%) than in the pre-1992 birth cohort (1.67%). The estimated incidences of TT-HBV occurring from one-time donors, repeat donors, post-1992 birth cohort donors, and pre-1992 birth cohort donors were 20.76, 13.84, 0.82, and 20.98 per 104 person-years, respectively.Conclusion: Our findings indicate a decreasing trend in HBV prevalence among blood donors in Southwestern China over the 6-year study period. This decline may be attributed to the widespread administration of HBV vaccinations and stringent screening measures implemented by blood donation centers. Continuous monitoring for HBV among blood donors is necessary to evaluate the effectiveness of preventive measures and inform future strategies to reduce transmission.Keywords: hepatitis B virus, transfusion-transmitted infections, epidemiology, vaccination

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

Mei Liu,1,&ast; Sili Guo,1,&ast; Xiaohan Li,1,&ast; Yang Tian,1 Yanjie Yu,2 Lili Tang,1 Qimei Sun,1 Ting Zhang,1 Mingwei Fan,3 Lili Zhang,1 Yingjiang Xu,4 Jiajia An,5 Xiangqian Gao,6 Lei Han,7 Lei Zhang1 1Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 2Department of Ultrasound Medicine, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 3Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 4Department of Interventional Vascular Surgery, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 5Department of Clinical Laboratory, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 6Department of Pathology, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 7Department of Reproductive Medicine, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Zhang, Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China, Email binzhouzhanglei@outlook.comBackground: GLP-1 receptor agonists (GLP-1 RA) have been proven to treat several metabolic diseases; however, the effects of GLP-1 RA on polycystic ovary syndrome (PCOS) remain unclear. Here, we aimed to investigate whether semaglutide, a novel GLP-1 RA, could alleviate ovarian inflammation in PCOS mice.Methods: Female C57BL/6J mice were subcutaneously injected with dehydroepiandrosterone for 21 days to establish the PCOS model. Then the mice were randomly divided into three groups: PCOS group (n = 6), S-0.42 group (semaglutide 0.42 mg/kg/w, n = 6), and S-0.84 group (semaglutide 0.84 mg/kg/w, n = 6). The remaining six mice were used as controls (NC). After 28 days of intervention, serum sex hormones and inflammatory cytokine levels were measured. Hematoxylin and eosin staining was used to observe the ovarian morphology. Immunohistochemical staining was used to detect the relative expression of CYP19A1, TNF-α, IL-6, IL-1β, and NF-κB in ovaries. CYP17A1 and StAR were detected using immunofluorescence staining. Finally, the relative expressions of AMPK, pAMPK, SIRT1, NF-κB, IκBα, pIκBα, TNF-α, IL-6, and IL-1β were measured using Western blotting.Results: First, after intervention with semaglutide, the weight of the mice decreased, insulin resistance improved, and the estrous cycle returned to normal. Serum testosterone and IL-1β levels decreased significantly, whereas estradiol and progestin levels increased significantly. Follicular cystic dilation significantly improved. The expression of TNF-α, IL-6, IL-1β, NF-κB, CYP17A1, and StAR in the ovary was significantly downregulated, whereas CYP19A1 expression was upregulated after the intervention. Finally, we confirmed that semaglutide alleviates ovarian tissue inflammation and improves PCOS through the AMPK/SIRT1/NF-κB signaling pathway.Conclusion: Semaglutide alleviates ovarian inflammation via the AMPK/SIRT1/NF‑κB signaling pathway in PCOS mice.Keywords: GLP-1 receptor agonist, polycystic ovary syndrome, semaglutide, inflammation

Rongrong Zhang,1,&ast; Wenjun Xu,1,&ast; Hongquan Wei,1,&ast; Boshi Li,1 Yaoxing Wang,1 Xueqing He,1 Jun Cao,1 Xinyu He,1 Mingxiang Xu,1,2 Wenjie Lu,1 Youzhi Xu1 1College of Basic Medicine, Anhui Medical University, Hefei, 230032, People’s Republic of China; 2Center for Scientific Research, Anhui Medical University, Hefei, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youzhi Xu; Wenjie Lu, Email xuyouzhi@ahmu.edu.cn; wenjie63136@163.comPurpose: Currently, there is still no clear treatment for polycystic ovary syndrome (PCOS). YJKL has better therapeutic effects and lower toxic side effects for PCOS type infertility. This study aims to clarify the potential mechanism of YJKL Decoction in the treatment of PCOS based on network pharmacology and experiments verification.Patients and Methods: Network pharmacology and experimental validation approach were used to investigate the bioactive ingredients, critical targets and potential mechanisms of YJKL Decoction against PCOS. Firstly, we use network pharmacology methods to collect core targets, and then validate their effects on diseases through experiments.Results: Five core targets were screened, Threonine kinase 1 (AKT1), Cellular tumor antigen p53 (TP53), Tumor necrosis factor (TNF), Albumin (ALB) and Vascular endothelial growthfactor A (VEGFA). KEGG analysis showed that YJKL treatment for PCOS mainly include AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway and HIF-1 signaling pathway. The molecular docking results showed that compounds have higher affinity with targets. Finally, experimental results had shown that YJKL Decoction had an better therapeutic effects in the treatment of PCOS.Conclusion: Based on a systematic network pharmacology approach and experimental verification, our results comprehensively illustrated the active ingredients, potential targets, and molecular mechanism of YJKL for application to PCOS and helps to illustrate mechanism of action on a comprehensive level.Keywords: traditional Chinese Medicine, YJKL, polycystic ovary syndrome, PCOS, molecular docking, experimental validation

Yapu Liu, Yuanyuan Su, Zhonghao Luan, Xiuwei Hou, Guangliang Wu, Yonghui Xu, Songmao Wang, Lifeng Gao, Xiaochen Zheng Department of Spinal Surgery, Second Affiliated Hospital of Luohe Medical College, Luohe, People’s Republic of ChinaCorrespondence: Yapu Liu, Department of Spinal Surgery, Second Affiliated Hospital of Luohe Medical College, 463 Haihe Avenue, Luohe, 462300, People’s Republic of China, Tel/Fax +86-0395-6162312, Email 460547380@qq.comPurpose: To introduce the surgical methods and clinical results of percutaneous vertebroplasty (PVP) combined with hollow screw placement as a treatment for patients with Kummell’s disease and pedicle rupture.Methods: From January 2020 to January 2023, a total of 10 patients with Kummell’s disease and pedicle rupture confirmed via imaging underwent three-column intensive therapy using hollow screws combined with PVP. There were two males and eight females with an average age 75.7± 6.11 years old. The time of operation, bone cement injection amount, bone cement leakage during operation were recorded. X-ray and CT were reexamined after operation. The improvement in quality of life was assessed using the Oswestry Disability Index (ODI), and the improvement in low back pain was assessed using the visual analogue scale (VAS).Results: Hollow screw placement combined with PVP was successfully performed in all patients. The average operation time was 39.2± 5.1 min, and the average volume of bone cement injected was 5.85± 0.83mL. No leakage of bone cement into spinal canal occurred.The mean preoperative ODI score was 75.70± 4.39, but this decreased significantly postoperatively(P< 0.05), being 37.70± 6.95 at 1 day and 26.40± 4.90, 23.70± 4.87, 21.70± 5.46, and 20.50± 4.21 at 1, 3, 6, and 12 months after the operation, respectively. The mean VAS pain score before the operation was 8.35± 0.63, but the symptoms of back pain were significantly relieved after operation(P< 0.05). The mean VAS scores 1 day and 1, 3, 6, and 12 months after the operation were 3.45± 0.47, 2.55± 0.60, 1.89± 0.48, 1.50± 0.27, and 1.12± 0.20, respectively.Conclusion: Hollow screw placement combined with percutaneous vertebroplasty serves as a valuable three-column intensive treatment for patients with Kummell’s disease and pedicle rupture. This procedure has the advantages of minimal trauma, less pain and quick recovery. The strong anchoring of bone cement and hollow screws provides stable and firm healing conditions for vertebral and pedicle fractures.Keywords: three-column enhancement, PVP, hollow screw, Kummell’s disease, pedicle rupture

Lei Gao,1,2,&ast; Yidi Xu,1,2,&ast; Xixue Zhang,1,2 Zhaoshun Jiang,1,2 Jiajun Wu,1,2 Yanjun Dong,1,2 Ming Li,3 Liang Jin,3 Jianjian Qiu,4 Lijue You,5 Chunhui Qin,6 Weidong Gu1,2 1Department of Anaesthesiology, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 3Department of Radiology, Huadong Hospital affiliated to Fudan University, Shanghai, People’s Republic of China; 4Department of Radiation Oncology, Huadong Hospital affiliated to Fudan University, Shanghai, People’s Republic of China; 5Department of Computer Center, Huadong Hospital affiliated to Fudan University, Shanghai, People’s Republic of China; 6Department of Pain Management, Yueyang Integrated Traditional Chinese Medicine and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weidong Gu, Email hdmz0800@163.comBackground: Performing spinal anaesthesia in elderly patients with ligament calcification or hyperostosis is challenging for novice practitioners. This pilot study aimed to compare the effectiveness of mixed reality-assisted spinal puncture (MRasp) with that of landmark-guided spinal puncture (LGsp) by novice practitioners in elderly patients.Methods: In this pilot study, 36 patients (aged ≥ 65 years) scheduled for elective surgery under spinal anaesthesia by anaesthesiology residents were included. Patients were randomly assigned to the MRasp group (n = 18) or the LGsp group (n = 18). The outcomes included the number of needle insertion attempts, redirection attempts, passes, the rate of successful first-attempt needle insertion, the rate of successful first needle pass, the spinal puncture time, the total procedure time, and the incidence of perioperative complications.Results: The median number of needle insertion attempts was significantly fewer in the MRasp group than in the LGsp group (1.0 vs 2.0, P = 0.023). The proportion of patients with successful first-attempt needle insertion was 72.2% in the MRasp group and 44.4% in the LGsp group (P = 0.176). The incidence of perioperative complications did not significantly differ between the two groups.Conclusion: This pilot study found that novice practitioners made significantly fewer needle insertion attempts in the MRasp group compared to the LGsp group when performing spinal anaesthesia on elderly patients. A future randomized controlled trial (RCT) is warranted to validate its effectiveness.Trial Registration: This trial was registered at https://www.chictr.org.cn/showproj.html?proj=178960 (ChiCTR-IPR-2300068520). Public title: Mixed reality-assisted versus landmark-guided spinal puncture in elderly patients: a randomized controlled pilot study. Principal investigator: Lei Gao. The registration date was February 22, 2023. The date of the first participant enrolment was February 27, 2023.Plain Language Summary: We developed virtual spine-presenting technology and patented optimal trajectory design technology to assist in spinal puncture and reported that the median number of needle insertion attempts was significantly fewer in the mixed reality-assisted spinal puncture group than in the landmark-guided spinal puncture group.Keywords: augmented reality, computer simulation, mixed reality, spinal puncture

Yidan Xu,1,&ast; Lu Zhang,1,&ast; Zhiyang Chen,1 Xiaonan Sun,1 Mengdan Zhao,1 Qirui Wu,2 Jiqing Hao1 1Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiqing Hao, Department of Oncology, The First Affiliated Hospital of Anhui Medical University, 81 Meishan Road, Hefei, Anhui, People’s Republic of China, Tel +86-13965029739, Email haojiqing@ahmu.edu.cnPurpose: This study aims to explore the association of inflammatory markers such as the Systemic Immune-Inflammatory Index (SII) and LANR with the comorbidity of Chronic Obstructive Pulmonary Disease (COPD) and lung cancer.Patients and Methods: A cross-sectional analysis was conducted on the clinical data of 309 patients with COPD only and 193 patients with COPD and lung cancer who attended the First Affiliated Hospital of Anhui Medical University. Additionally, we examined autonomous risk factors that contribute to the simultaneous development of COPD and lung cancer through univariate and multivariate logistic regression analyses. This analysis resulted in the development of a nomogram model for visual representation. The effectiveness of the model was assessed using a receiver operating characteristic (ROC) curve, calibration curve, and clinical decision analysis (DCA) curve, with internal validation conducted via repeated sampling methods.Results: Multivariate analysis of clinical characteristics and inflammatory markers showed that smoking history of > 60 pack-years, hemoptysis, emphysema, WBC count > 5.53 (× 10^9/L), SII > 629.285, and LANR < 11.39 were significantly associated with the comorbidity of COPD and lung cancer. These factors were subsequently integrated into the nomogram model. The AUC of the model stood at 0.849 (95% CI: 0.815– 0.882), demonstrating a notable improvement over the COPD-LUCSS scoring system (AUC: 0.716, 95% CI: 0.671– 0.761). The DCA curve indicated a notable clinical advantage provided by the model. Additionally, patients with stage IV tumors exhibited elevated SII levels and reduced LANR levels compared to earlier stages, indicating potential prognostic significance for both markers.Conclusion: Increased levels of the inflammatory markers SII and LANR are associated with the risk of comorbidity of COPD and lung cancer.Keywords: lung cancer, inflammation, systemic immune-inflammation index, nomogram, LANR, chronic obstructive pulmonary disease

Zhiying Yang,1,&ast; Shun Yao,1,2,&ast; Yichong Xu,1 Xiaoqing Zhang,1,2 Yuan Shi,1,2 Lijun Wang,1,2 Donghong Cui1,2 1Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Psychotic Disorders, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Donghong Cui, Email manyucc@126.comBackground: Schizophrenia is a devastating mental disease with high heritability. A growing number of susceptibility genes associated with schizophrenia, as well as their corresponding SNPs loci, have been revealed by genome-wide association studies. However, using SNPs as predictors of disease and diagnosis remains difficult. Here, we aimed to uncover susceptibility SNPs in a Chinese population and to construct a prediction model for schizophrenia.Methods: A total of 210 participants, including 70 patients with schizophrenia, 70 patients with bipolar disorder, and 70 healthy controls, were enrolled in this study. We estimated 14 SNPs using published risk loci of schizophrenia, and used these SNPs to build a model for predicting schizophrenia via comparison of genotype frequencies and regression. We evaluated the efficacy of the diagnostic model in schizophrenia and control patients using ROC curves and then used the 70 patients with bipolar disorder to evaluate the model’s differential diagnostic efficacy.Results: 5 SNPs were selected to construct the model: rs148415900, rs71428218, rs4666990, rs112222723 and rs1716180. Correlation analysis results suggested that, compared with the risk SNP of 0, the risk SNP of 3 was associated with an increased risk of schizophrenia (OR = 13.00, 95% CI: 2.35– 71.84, p = 0.003). The ROC-AUC of this prediction model for schizophrenia was 0.719 (95% CI: 0.634– 0.804), with the greatest sensitivity and specificity being 60% and 80%, respectively. The ROC-AUC of the model in distinguishing between schizophrenia and bipolar disorder was 0.591 (95% CI: 0.497– 0.686), with the greatest sensitivity and specificity being 60% and 55.7%, respectively.Conclusion: The SNP risk score prediction model had good performance in predicting schizophrenia. To the best of our knowledge, previous studies have not applied SNP-based models to differentiate between cases of schizophrenia and other mental illnesses. It could have several potential clinical applications, including shaping disease diagnosis, treatment, and outcomes.Keywords: schizophrenia, SNP, diagnostic model, bipolar disorder, differential diagnosis

Hui Huang,1– 3,&ast; Qing Ye,1– 4,&ast; Yulan Xu,1– 3,&ast; Baoming Tao,1– 3 Junlan Liu,1– 3 Tian Xie,1– 3 Lingfeng Zha1– 3 1Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4School of Nursing, Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tian Xie; Lingfeng Zha, Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People’s Republic of China, Tel +86-15972150162 ; +86-15827177185, Email xietian@hust.edu.cn; zhalf@hust.edu.cnPurpose: We investigated the risk factors and characteristic clinical features of peripartum cardiomyopathy (PPCM) to lay the groundwork for early identification, screening, diagnosis, and intervention in high-risk pregnant women.Patients and methods: A retrospective case-control study was conducted to analyze data from 44 patients with PPCM and 226 normal pregnant women from a Chinese population.Results: Significant differences were found between the groups in terms of various factors such as age, body mass index (BMI), heart rate, and medical history. Logistic regression models identified abnormal electrocardiography (OR=18.852), upper respiratory tract infection (OR=41.822), gestational hypertension (OR=18.188), and cesarean section (OR=8.394) as risk factors for PPCM. Common clinical features observed in patients with PPCM included cough, wheezing, and chest tightness (68.18%), left heart enlargement (56.82%) and valvular insufficiency (81.82%). Additionally, cardiotropic virus was detected in a subset of patients (43.18%) and NT-proBNP was elevated ≥ 400 pg/mL (81.82%).Conclusion: In the Chinese population, the presence of abnormal electrocardiograms during pregnancy, history of upper respiratory tract infection, gestational hypertension, and maternal choice of cesarean section suggest the possibility of PPCM development. Factors such as advanced age, family history of cardiovascular disease, gestational diabetes mellitus, eclampsia, anemia, and hypoproteinemia should be considered. Clinically, patients present with cough, wheezing, chest tightness, enlarged left heart, valvular insufficiency and NT-proBNP elevated ≥ 400 pg/mL. This study could serve as a valuable reference for medical practitioners for the early identification and screening of patients with PPCM.Keywords: peripartum cardiomyopathy, risk factors, clinical features, early identification

Yue Xu,1,&ast; Shuhong Zhang,1,&ast; Ping Wang,1,&ast; Yuanyuan Chen,1 Yazhan Mao,2 Xina Yuan,3 Yinyi Li,4 Mingming Li,1 Li Sheng,1 Xiaoqian Li,1 Na Gao1 1Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Respiratory, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China; 3College of Pulmonary and Critical Care Medicine, The Eighth Medical Center, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China; 4Department of Outpatient, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Na Gao; Xiaoqian Li, Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, 100853, People’s Republic of China, Tel +86 18515165409, Email gaona301s@163.com; 41705763@qq.comObjective: This study aims to explore the correlates of frailty in hospitalized elderly hypertensive patients and its impact on clinical prognosis, and to construct a predictive model for the occurrence of frailty in this population.Methods: A cross-sectional and prospective observational cohort study was conducted, involving 312 elderly hypertensive patients diagnosed at the institution from January to June 2022. Frailty was diagnosed using the Fried Frailty Phenotype (FP), while the Charlson Comorbidities Index (CCI) assessed the presence of chronic conditions. Data analysis was performed using SPSS 22.0. Binary logistic regression analysis was conducted with frailty as the dependent variable to identify risk factors. Patients were followed for one year to monitor readmission rates and all-cause mortality.Results: Multivariate logistic regression identified CCI grade (P=0.030), gender (OR=21.618, 95% CI: 4.062– 115.061, P < 0.001), age (OR=1.147, 95% CI: 1.086– 1.211, P < 0.001), bedridden state (OR=11.620, 95% CI: 3.282– 41.140, P < 0.001), arrhythmia (OR=14.414, 95% CI: 4.558– 45.585, P < 0.001), heart failure (OR=5.439, 95% CI: 1.029– 28.740, P < 0.05), along with several biochemical markers, as independent predictors of frailty. A predictive model was developed, demonstrating a robust discriminative ability with an area under the receiver operating characteristic curve (AUC) of 0.915. Statistically significant differences in readmission rates and all-cause mortality were observed among the frail, pre-frail, and non-frail groups (P< 0.001), with the frail group exhibiting the highest incidence of these adverse outcomes. Notably, frailty emerged as a significant predictor of readmission (P< 0.05) but not of all-cause mortality in this cohort.Conclusion: This study establishes a robust frailty prediction model for elderly hypertensive patients, highlighting the influence of CCI grade, gender, age, and other clinical and biochemical factors on frailty. The model offers a valuable tool for healthcare providers to identify at-risk elderly individuals, facilitating targeted intervention strategies for cardiovascular disease management.Keywords: frailty, hypertension, older people, observational study, prediction model

Longyi Zheng,1,&ast; Chengjing Zhang,2,&ast; Shichang Bu,1,&ast; Wencheng Guo,3,&ast; Tongtong Li,4 Ying Xu,5 Yunan Liu,4 Caimei Yuan,4 Chengwu Feng,4 Geng Zong,4 Jingwen Zhu,4 Maoying Xing,5 Xin Geng5 1Department of Endocrinology, Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Nutrition, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, People’s Republic of China; 3Department of General Surgery and Vascular Surgery, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 4CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China; 5National Center for Liver Cancer, Naval Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Maoying Xing; Xin Geng, Email xmyxing@sina.com; gxouc@hotmail.comBackground: Neuregulin 4 (NRG4) was known to be associated with serum lipid levels and atherosclerosis. However, it is unknown whether the role of NRG4 in lipid homeostasis is causal to atherosclerosis and whether the effect is beneficial across different atherosclerosis subtypes.Methods: We investigated the causal role of the levels of serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides regulated by NRG4 in subtypes of atherosclerosis through two sample Mendelian randomization. Aggregated genome-wide association study (GWAS) summary data for serum lipid level of 1.32 million individuals with European ancestry were obtained from the Global Lipids Genetics Consortium. GWAS summary data for four atherosclerosis subtypes (peripheral, coronary, cerebral and the other atherosclerosis) were obtained from FinnGen Consortium. Generalized inverse-variance–weighted Mendelian randomization and several sensitivity analyses were used to obtain the causal estimates.Results: A 1-SD genetically elevated LDL-C level mediated by NRG4 was validated to be nominally associated with the risk of peripheral atherosclerosis (log (odds ratio)= 4.14, 95% confidence interval 0.11 to 8.17, P = 0.04), and the other associations were not significant or could not be validated by sensitivity analyses.Conclusion: LDL-C lowering mediated by NRG4 is likely to prevent peripheral atherosclerosis.Keywords: Mendelian randomization analysis, NRG4, atherosclerosis, lipid

Wei Tang,1,2,&ast; Ying Liu,3,&ast; Xin Li,2 Guiyun Leng,2 Ju Gao,2 Yawu Wang,2 Jie Yao,2 Zhou Liu,2 Qiang Zhou,2 Yuanhong Xu1 1Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2Department of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of China; 3High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhong Xu, Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei, Anhui, 230022, People’s Republic of China, Tel +86 135 0569 4447, Fax +86 551 6292 2125, Email xyhong1964@ahmu.edu.cnPurpose: This study aimed to investigate the microbiological characteristics of clinically isolated Staphylococcus aureus with different hemolytic phenotypes in China.Materials and Methods: Using the three-point inoculation method, the hemolytic phenotypes of 1295 clinically isolated S. aureus strains were detected and categorized. Antimicrobial susceptibility testing of all strains was performed using a VITEK 2 Compact System. After sample size matching, plasma coagulase activity, catalase activity, mRNA expression of hemolysin genes (hla, hlb, hlc, and hld), biofilm formation, growth kinetics, inflammatory response of macrophages and cytotoxicity of S. aureus with different hemolytic phenotypes using the rabbit plasma kit, the catalase test on slides, qRT-PCR, crystal violet staining, the microcultivation assay, the ELISA kits, and the CCK-8 assay, respectively.Results: Seven categories of hemolytic phenotypes were identified. Accordingly, strains were categorized into seven different groups, including S. aureus with complete hemolytic phenotype (SCHP), S. aureus with weak hemolytic phenotype (SWHP), S. aureus with incomplete hemolytic phenotype 1 (SIHP-1), SIHP-2, SIHP-3, SIHP-4 and SIHP-5, the last three of which were reported for the first time. Except for the hemolytic phenotype, all seven groups differed in clinical isolation rates, antibiotic resistance profile, plasma coagulase activity, mRNA expression of hemolysin genes, biofilm formation, growth kinetics, inflammatory response of macrophages, and cytotoxicity.Conclusion: S. aureus with different hemolytic phenotypes have distinctive microbiological characteristics. Clinical microbiologists need to be vigilant about the hemolytic phenotypes when culturing S. aureus strains, and actively enhance communication with clinicians to optimize the treatment of infection.Keywords: Staphylococcus aureus, hemolytic phenotype, hemolysin, microbiological characteristics, antibiotic resistance

Qing Zhang, Yao Xu, Hao Wang, Xuelian Pang, Qingfeng Meng Department of Cardiology, Qilu Hospital of Shandong University, Qingdao, People’s Republic of ChinaCorrespondence: Xuelian Pang; Qingfeng Meng, Email pxl18561810097@163.com; mengfeng0912@163.comAbstract: Transcatheter aortic valve replacement (TAVR) has been recently indicated for the treatment of patients with severe aortic stenosis in all risk profiles. At present, TAVR has become mature at home and abroad, but the relevant experience is deficient in the treatment of aortic valve stenosis with outflow tract stenosis. One case of a high-risk surgical patient was included in this paper who suffered from severe aortic valve stenosis with left ventricular outflow tract (LVOT) stenosis. In this case, TAVR was performed with deep implantation of a new valve and both aortic valve stenosis and LVOT stenosis were treated through a single TAVR procedure. This case highlights the vital role of such treatment in dealing with both aortic valve stenosis and LVOT stenosis through a single TAVR procedure, thus providing valuable information for similar cases.Keywords: severe aortic valve stenosis, left ventricular outflow tract, LVOT, stenosis, transcatheter aortic valve replacement, TAVR

Mingming Chen,1 Shuting Chang,1 Yunpeng Xu,1 Hong Guo,2 Jian Liu1,3 1The First Clinical Medical College of Lanzhou University, Lanzhou City, Gansu Province, People’s Republic of China; 2Department of Critical Care Medicine, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou City, Gansu Province, People’s Republic of China; 3Gansu Provincial Maternity and Child-Care Hospital (Gansu Provincial Center Hospital), Lanzhou City, Gansu Province, People’s Republic of ChinaCorrespondence: Jian Liu, Department of Clinical Medicine, The First Clinical Medical College of Lanzhou University, No. 1, Donggang West Road, Chengguan District, Lanzhou City, Gansu Province, People’s Republic of China, Tel +86 136 0935 4197, Email medecinliujian@163.comAbstract: Chronic Obstructive Pulmonary Disease (COPD) exerts a severe toll on human health and the economy, with high prevalence and mortality rates. The search for bioactive components effective in the treatment of COPD has become a focal point of research. Beetroot juice, readily accessible and cost-effective, is noted for its ability to enhance athletic performance and for its preventive and therapeutic impact on hypertension. Beetroot juice is a rich source of dietary nitrates and modulates physiological processes via the nitrate-nitrite- nitric oxide pathway, exerting multiple beneficial effects such as antihypertensive, bronchodilatory, anti-inflammatory, antioxidant, hypoglycemic, and lipid-lowering actions. This paper provides a review of the existing research on the effects of beetroot juice on COPD, summarizing its potential in enhancing exercise capacity, lowering blood pressure, improving vascular function, and ameliorating sleep quality among patients with COPD. The review serves as a reference for the prospective use of beetroot juice in the symptomatic improvement of COPD, as well as in the prevention of exacerbations and associated comorbidities.Keywords: chronic obstructive pulmonary disease, beetroot, nitrates, nitric oxide, exercise, vascular function

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

Ruijie Zhang,1,&ast; Xinran Dong,2,&ast; Lu Zhang,1,&ast; Xinao Lin,1 Xuefeng Wang,1 Yan Xu,3 Chuyan Wu,4 Feng Jiang,1 Jimei Wang1 1Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of China; 2Center for Molecular Medicine, Children’s Hospital of Fudan University, Shanghai, People’s Republic of China; 3Department of Neurology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, People’s Republic of China; 4Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jimei Wang; Feng Jiang, Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of China, Email wjm821920@163.com; dxyjiang@163.comBackground: Neonatal sleep is pivotal for their growth and development, yet manual interpretation of raw images is time-consuming and labor-intensive. Quantitative Electroencephalography (QEEG) presents significant advantages in terms of objectivity and convenience for investigating neonatal sleep patterns. However, research on the sleep patterns of healthy neonates remains scarce. This study aims to identify QEEG markers that distinguish between different neonatal sleep cycles and analyze QEEG alterations across various sleep stages in relation to postmenstrual age.Methods: From September 2023 to February 2024, full-term neonates admitted to the neonatology department at the Obstetrics and Gynecology Hospital of Fudan University were enrolled in this study. Electroencephalographic (EEG) recordings were obtained from neonates aged 37– 42 weeks, within 1– 7 days post-birth. The ROC curve was employed to evaluate QEEG features related to amplitude, range EEG (rEEG), spectral density, and connectivity across different sleep stages. Furthermore, regression analyses were performed to investigate the association between these QEEG characteristics and postmenstrual age.Results: The alpha frequency band’s spectral_diff_F3 emerged as the most potent discriminator between active sleep (AS) and quiet sleep (QS). In distinguishing AS from wakefulness (W), the theta frequency’s spectral_diff_C4 was the most effective, whereas the delta frequency’s spectral_diff_P4 excelled in differentiating QS from W. During AS and QS phases, there was a notable increase in entropy within the delta frequency band across all monitored brain regions and in the spectral relative power within the theta frequency band, correlating with postmenstrual age (PMA).Conclusion: Spectral difference showcases the highest discriminative capability across awake and various sleep states. The observed patterns of neonatal QEEG alterations in relation to PMA are consistent with the maturation of neonatal sleep, offering insights into the prediction and evaluation of brain development outcomes.Keywords: quantitative EEG, neonates, sleep, postmenstrual age

Wei Xiang, Zhen Guo, Yiming Zhang, Yuanzhi Xu Department of Stomatology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of ChinaCorrespondence: Yuanzhi Xu; Yiming Zhang, Email amyxyz01@Hotmail.com; 1701086@tongji.edu.cnBackground: Hypertrophic scars (HS) are dermal diseases characterized by excessive fibroblast proliferation and collagen deposition following burns or trauma. While Tenascin-C (TNC)’s role in promoting visceral fibrosis has been established, its impact on skin tissue fibrosis remains unclear. This study aims to investigate the effects of TNC on HS.Methods: RNA sequence and IHC techniques were used to examine the upregulation of TNC gene in human hypertrophic scar tissue compared to normal tissues. Knockdown of TNC in Human skin fibroblasts (HFF-1) cells was achieved, and expression of Col1 and Col3 was evaluated using qPCR. Sirius red collagen staining assessed impact on total collagen content and ECM deposition. Effects on cell proliferation and migration were investigated through cck-8 and cell scratch experiments. Lentivirus infection was used to knock out TNC, and resulting samples were injected into ear wound of rabbits. Effects of TNC knockout on ear scar formation were measured using digital morphology, ultrasound, SEI, H&E, and Masson trichrome methods.Results: Cell experiments: downregulation of TNC decreased Col1 and Col3 expression, leading to reduced collagen production and extracellular matrix deposition. It did not affect HFF-1 cell proliferation and migration. Animal experiments: TNC knockdown promoted wound healing and reduced collagen deposition in rabbit ears.Conclusion: This study suggests that knocking down TNC inhibits collagen formation and extracellular matrix deposition, thereby inhibiting hypertrophic scar formation. Therefore, TNC can be considered a potential biomarker for HS formation and may offer promising treatment strategies for clinical management of hypertrophic scars.Keywords: Tenascin-C, hypertrophic scars, rabbit ear scar model, HFF-1

Xingyuan Li,1,2,&ast; Fenghao Yang,3,&ast; Nan Li,4,&ast; Yong Xu,5 Fang Liu1,2 1Department of Nephrology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Laboratory of Diabetic Kidney Disease, Kidney Research Institute, Department of Nephrology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Department of Psychiatry, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Liu, West China Hospital, Sichuan University, &num;37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-18980601214, Fax +86-28-85422335, Email liufangfh@163.comBackground: Diabetic kidney disease (DKD) patients require comprehensive disease education and mutual support to cope with various challenges. Social media platforms provide opportunities for DKD patients to access information and interact with peers. However, qualitative analysis of DKD patients’ real-world concerns and needs on social media is lacking.Methods: A qualitative study was conducted to analyze DKD patients’ posts on Facebook and Baidu DKD-specific forums from June 2013 to June 2023. Posts were retrieved, and the forum with the most DKD-related posts from each platform was selected using stratified random sampling. Thematic analysis was performed to identify common themes, which were categorized and quantified.Results: In total, 746 DKD-related posts were analyzed, generating 203 keyword categories with 954 tags. Three main themes emerged: Diagnosis and Comorbidities (50.2%), Treatment and Prevention (29.7%), and Lifestyle and Psychology (20.1%). Patients were most concerned about DKD diagnosis, staging, comorbidities, and interpreting diagnostic indicators. They also sought information on treatment advancements, medications, renal replacement therapies, and traditional Chinese medicine. Diet, exercise, work-life balance, family planning, and mental well-being were key lifestyle and psychological concerns.Conclusion: This study reveals DKD patients’ primary needs and concerns on social media, which can guide healthcare professionals in providing targeted education and support. Meeting patients’ needs through comprehensive education and counseling can improve treatment adherence and prognosis, though challenges remain in addressing all issues in real-world practice.Keywords: diabetic kidney disease, qualitative research, patient education, social media

Yuan Gao,1– 3,&ast; Ce Zong,1,&ast; Ying Yao,4 Haixu Zhao,5 Yuan Song,4 Ke Zhang,1 Hongxun Yang,1 Hongbing Liu,1 Yunchao Wang,1 Yusheng Li,1– 3 Jing Yang,1– 3 Bo Song,1– 3 Yuming Xu1– 3 1Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, People’s Republic of China; 3Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou, Henan, People’s Republic of China; 4School of Health and Nursing, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 5School of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuming Xu, Department of Neurology, the First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Erqi District, Zhengzhou, Henan Province, People’s Republic of China, 450052, Tel/Fax +86 13903711125, Email xuyuming@zzu.edu.cnPurpose: We aimed to explore the association between fibrinogen-to-albumin ratio (FAR) and the risk of incident stroke (IS) in a cohort of cerebral small vessel disease (CSVD) patients.Patients and Methods: Participants were screened from a prospective CSVD database. Clinical data, hematologic measures and imaging findings were collected. The primary outcome was IS during follow-up, with a secondary outcome of composite vascular events (CVE) including IS, myocardial infarction (MI), and vascular deaths. Univariate and multivariate COX proportional risk models, along with competing risk models, were employed to identify factors associated with outcomes. Restricted cubic spline (RCS) and subgroup analyses were conducted to assess the association between FAR and the risk of IS and CVE in CSVD patients.Results: In the final analysis of 682 CSVD patients over a median observation period of 34.0 [24.0– 53.0] months, there were 33 cases of IS (4.84%, 1.55/100 person-years), 4 incidents of MI (0.59%, 0.19/100 person-years), 15 non-vascular deaths (2.20%, 0.70/100 person-years), and 37 occurrences of CVE (5.43%, 1.74/100 person-years). Multivariate Cox regression analysis revealed a significant positive correlation between elevated FAR and both IS (HR 1.146; 95% CI 1.043– 1.259; P=0.004) and CVE (HR 1.156; 95% CI 1.063– 1.257; P=0.001) in CSVD patients. Multivariate competing risk model showed the similar results (IS: HR 1.16; 95% CI 1.06– 1.27; P=0.001, CVE: HR 1.15; 95% CI 1.05– 1.26; P=0.003). RCS analysis indicated a linear relationship between FAR and the risks of both IS (P for non-linearity =0.7016) and CVE (P for non-linearity =0.6475), with an optimal cutoff value of 8.69, particularly in individuals over 60 years of age.Conclusion: Elevated FAR demonstrated an independent and linear association with IS and the development of CVE in CSVD patients.Keywords: cerebral small vessel disease, incident stroke, fibrinogen-to-albumin ratio, inflammation

Ningning Wang, Yuanyuan Xu, Guangde Yang, He Chen, Xia Wang, Juanjuan Fu, Li Li, Xiucheng Pan Department of Infectious Disease, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Xiucheng Pan, Email xzpxc68@126.comPurpose: There is limited research on whether Proton Pump Inhibitors (PPIs) will affect the efficacy of immune checkpoint inhibitors (ICIs) in treating hepatocellular carcinoma (HCC).This study aimed to determine whether PPIs affect the survival outcomes of patients with HBV-associated advanced HCC receiving combination therapy based on ICIs.Methods: We retrospectively analyzed patients with hepatitis B virus (HBV)-associated advanced HCC who underwent ICIs combination therapy from January 1, 2020, to December 30, 2022. Patients were stratified into PPI and non-PPI groups based on whether they received PPI treatment within 30 days before or after ICIs therapy. Patients’ survival and the risk of PPI-associated mortality was assessed. Adverse events were also evaluated.Results: A total of 183 patients with HBV-associated HCC treated with ICI combination therapy were included. The median survival time (12.5 months vs 13.7 months, P = 0.285) and incidence of adverse events (P = 0.729) did not significantly differ between the PPI and non-PPI groups. Even after propensity score matching, the difference in median overall survival (OS) between the two groups was not significant (10.7 months vs 11.4 months; P = 0.596) and the patient’s OS is not significantly related to the dosage of PPI application (P > 0.05).However, according to our subgroup analysis, among HCC patients with a serum HBV DNA concentration ≥ 200 IU/mL, the use of PPIs significantly increased the risk of mortality in patients receiving ICI combination therapy (P = 0.024).Conclusion: PPIs do not notably influence the survival prognosis of patients receiving ICI combination therapy for HBV-associated advanced HCC. However, among patients with high levels of HBV DNA, PPIs increase the risk of mortality. Therefore, antiviral therapy should be intensified in the patients with HBVDNA > 200 IU/mL. Additionally, PPIs do not impact the incidence of adverse reactions in these patients.Keywords: hepatocellular carcinoma, immune checkpoint inhibitors, proton pump inhibitors, chronic hepatitis B virus infection

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

Geyi Wen,1,&ast; Jinliang Meng,1,&ast; Puxian Peng,2,&ast; Yanyan Xu,1 Ruiqi Wang,1 Wenlong Cui,2 Aihan Wen,2 Guohong Luo,2 Yunhui Zhang,1 Songyuan Tang2 1Department of Pulmonary and Critical Care Medicine, the First People’s Hospital of Yunnan Province, the Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China; 2Institute of Health Studies, School of Public Health, Kunming Medical University, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunhui Zhang, Department of Pulmonary and Critical Care Medicine, the First People’s Hospital of Yunnan Province, No. 157 Jinbi Road, Xishan District, Kunming, Yunnan, 650032, People’s Republic of China, Email yunhuizhang3188@126.com Songyuan Tang, Institute of Health Studies, School of Public Health, Kunming Medical University, 1168 West Chunrong Road, Yuhua Street, Chenggong District, Kunming, Yunnan, 650500, People’s Republic of China, Email tsythailand@hotmail.comPurpose: Chronic obstructive pulmonary disease (COPD) is a significant disease impacting health and quality of life. Yunnan Province, a major tobacco producer, lacks comprehensive COPD studies. The purpose of this study is to describe the epidemic situation of COPD in Yunnan province and explore its influencing factors.Methods: This study is a cross-sectional research conducted in a representative sample of adults aged 20 and older from 13 prefectures and cities in Yunnan Province, China. COPD was diagnosed using post-bronchodilator pulmonary function tests. Demographics were analyzed with descriptive statistics. The influencing factors of COPD were examined by using the multivariate logistic regression models.Results: Our study found that high-risk individuals for COPD accounted for 20.30% of the screened population aged 20 and above, with a COPD prevalence of 27.18% among this high-risk group. Male had a higher prevalence (33.01%) than did female (16.35%; p< 0.001 for sex difference). Additionally, the proportion of severe and extremely severe COPD cases in Yunnan Province was higher than the national average and other provinces. After considering the potential confounding variables, male (OR=2.291, 95% CI: 1.584– 3.313), age (OR=1.501, 95% CI: 1.338– 1.685), underweight (OR=1.747, 95% CI: 1.225– 2.491), previous smoking (OR=1.712, 95% CI: 1.182– 2.478), passive smoking (OR=1.444, 95% CI: 1.159– 1.800), and a history of respiratory system diseases in childhood (OR=2.010, 95% CI: 1.346– 3.001) were significantly associated with an increased risk of COPD. Conversely, being overweight (OR=0.636, 95% CI: 0.489– 0.828), and residing in high-altitude counties (OR=0.445, 95% CI: 0.263– 0.754) were negatively correlated with the risk of COPD.Conclusion: There is significant prevalence of COPD (27.18%) among high-risk population aged 20 and above in Yunnan Province, China. Apart from male, smoking, BMI and other known risk factors for COPD. We found that high-altitude residence had a lower prevalence of COPD. There is no significant difference in COPD prevalence between Han and ethnic minority populations.Keywords: chronic obstructive pulmonary disease, epidemiological characteristics, influencing factors, high-risk population, China

Yuan Xu,1 Jie Song,1 Jie Gao,1 Hongjing Zhang2 1Department of Gastroenterology, Dongying People’s Hospital(Dongying Hospital of Shandong Provincial Hospital Group), Dongying, Shandong, People’s Republic of China; 2Community Health Service Center in Hekou District, Dongying, Shandong, People’s Republic of ChinaCorrespondence: Yuan Xu, Department of Gastroenterology, Dongying People’s Hospital (Dongying Hospital of Shandong Provincial Hospital Group), No. 317 Nanyi Road, Dongying, Shandong, 257091, People’s Republic of China, Email jry0919@sina.comPurpose: Oxidative stress promotes disease progression by stimulating the humoral and cellular immune responses. However, the molecular mechanisms underlying oxidative stress and immune responses in acute pancreatitis (AP) have not been extensively studied.Patients and Methods: We analyzed the GSE194331 dataset and oxidative stress-related genes (OSRGs). We identified differentially expressed immune cell-associated OSRGs (DE-ICA-OSRGs) by overlapping key module genes from weighted gene co-expression network analysis, OSRGs, and DEGs between AP and normal samples. Functional enrichment analysis was performed to investigate the functions of DE-ICA-OSRGs. We then filtered diagnostic genes using receiver operating characteristic curves and investigated their molecular mechanisms using single-gene set enrichment analysis (GSEA). We also explored the correlation between diagnostic genes and differential immune cells. Finally, we constructed a transcription factor-microRNA-messenger RNA (TF-miRNA-mRNA) network of biomarkers.Results: In this study, three DE-ICA-OSRGs (ARG1, NME8 and VNN1) were filtered by overlapping key module genes, OSRGs and DEGs. Functional enrichment results revealed that DE-ICA-OSRGs were involved in the cellular response to reactive oxygen species and arginine biosynthesis. Latterly, a total of two diagnostic genes (ARG1 and VNN1) were derived and their expression was higher in the AP group than in the normal group. The single-gene GSEA enrichment results revealed that diagnostic genes were mainly enriched in macroautophagy and Toll-like receptor signaling pathways. Correlation analysis revealed that CD8 T cells, resting memory T CD4 cells, and resting NK cells were negatively correlated with ARG1, and neutrophils were positively correlated with ARG1, which was consistent with that of VNN1. The TF-miRNA-mRNA regulatory network included 11 miRNAs, 2 mRNAs, 10 transcription factors (TFs), and 26 pairs of regulatory relationships, like NFKB1-has-miR-2909-VNN1.Conclusion: In this study, two immune cell oxidative stress-related AP diagnostic genes (ARG1 and VNN1) were screened to offer a new reference for the diagnosis of patients with AP. Keywords: acute pancreatitis, oxidative stress, diagnosis, immunity

Shiyu Wang,1– 4 Wei Qin,1– 4 Tingting Cheng,1– 4 Cong Zeng,1– 4 Xu Chen,1– 4 Yajing Xu1– 4 1Department of Hematology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Changsha, Hunan, People’s Republic of China; 3Hunan Hematologic Neoplasms Clinical Medical Research Center, Changsha, Hunan, People’s Republic of China; 4National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Soochow, Jiangsu, People’s Republic of ChinaCorrespondence: Yajing Xu, Department of Hematology, Xiangya Hospital, Central South University, &num;87 Xiangya Road, Changsha, Hunan, People’s Republic of China, Email xyyajingxu@csu.edu.cnPurpose: Acute graft-versus-host disease (aGVHD) poses a significant impediment to achieving a more favourable therapeutic outcome in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The tumour suppressor p53 plays a pivotal role in preventing aGVHD development. However, whether P53 pathway which contains p53 family members and other related genes participates in aGVHD development remains an unsolved question.Patients and Methods: Transcriptomic data was obtained from Gene Expression Omnibus (GEO) database. Gene set enrichment analysis was applied to determine the enrichment degree of signaling pathways. CIBERSORT and ssGSVA were used to evaluate immune cell compositions. Univariate and multivariate logistic regression analysis were performed to examine the independent diagnostic variables. qRT-PCR was utilized to validate the genes expression levels in our cohort.Results: A total number of 102 patients (42 aGVHD patients vs 60 non-aGVHD patients) were obtained after integrating two datasets in GEO database (GSE73809 and GSE4624). P53 pathway was remarkably suppressed in T cells from aGVHD patients and negatively associated with activated T cells as well as T cells activation related signaling pathways, including T-cell receptor (TCR), mTORC1, MYC and E2F target pathways. A risk model for aGVHD built by four genes (DDIT3, FBXW7, TPRKB and TOB1) in P53 pathway, exhibiting high differentiate and predictive value. DDIT3 and FBXW7 mRNA expression levels significantly decreased in peripheral blood mononuclear cells (PBMCs) from aGVHD patients compared with non-aGVHD group in our patient cohort, consisting with bioinformatics analysis.Conclusion: P53 pathway plays a potential role in impeding T cell activation through suppressing its related signaling pathways, thereby preventing aGVHD development. P53 pathway may emerge as a promising therapeutic target in aGVHD treatment.Keywords: allogeneic hematopoietic stem cell transplantation, aGVHD, P53 pathway, T cells, activation

Yuan Xu, Jing-Yan Wang, Yang Zou, Xue-Wei Ma, Tian Meng College of Health Industry, Sichuan Tourism University, Chengdu, Sichuan, 610100, People’s Republic of ChinaCorrespondence: Yuan Xu, Email 230973159@qq.comAbstract: Inflammatory cytokines, interleukin-36 (IL-36), IL-37, IL-38 belong to IL-1 family. The IL-36 subfamily obtains pro- and anti-inflammatory effects on various immune responses. Cytokine IL-37, has anti-inflammatory functions in immunity, and the recently identified IL-38 negatively associated with disease pathogenesis. To date, expression of IL-36, IL-37, IL-38 is reported dysregulated in osteoarthritis (OA) and rheumatoid arthritis (RA), and may be disease markers for arthritis-related diseases. Interestingly, expression of IL-38 was different either in OA patients or animal models, and expression of IL-36Ra in synovium was different in OA and RA patients. Moreover, functional studies have demonstrated significant role of these cytokines in OA and RA progress. These processes were related to immune cells and non-immune cells, where the cytokines IL-36, IL-37, IL-38 may regulate downstream signalings in the cells, and then involve in OA, RA development. In this review, we comprehensively discuss recent advancements in cytokines and the development of OA, RA. We hope that targeting these cytokines will become a potential treatment option for OA and RA in the future.Keywords: IL-36, IL-37, IL-38, osteoarthritis, rheumatoid arthritis

Tong Zhang,1– 3,&ast; Han Wu,1,2,&ast; Chenling Qiu,1,2 Mingxin Wang,1,2 Haiting Wang,1,2 Shunhua Zhu,1,4 Yinhai Xu,2 Qingli Huang,1,4 Shibao Li1,2 1Medical Technology School of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China; 2Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China; 3Chuzhou Center for Disease Control and Prevention, Chuzhou City, Anhui, 239000, People’s Republic of China; 4Public Experimental Research Center of Xuzhou Medical University, Xuzhou City, Jiangsu, 221004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingli Huang; Shibao Li, Email qlhuang@xzhmu.edu.cn; sdjnshlb@xzhmu.edu.cnIntroduction: Insulin and C-peptide played crucial roles as clinical indicators for diabetes and certain liver diseases. However, there has been limited research on the simultaneous detection of insulin and C-peptide in trace serum. It is necessary to develop a novel method with high sensitivity and specificity for detecting insulin and C-peptide simultaneously.Methods: A core-shell-satellites hierarchical structured nanocomposite was fabricated as SERS biosensor using a simple wet-chemical method, employing 4-MBA and DTNB for recognition and antibodies for specific capture. Gold nanorods (Au NRs) were modified with Raman reporter molecules and silver nanoparticles (Ag NPs), creating SERS tags with high sensitivity for detecting insulin and C-peptide. Antibody-modified commercial carboxylated magnetic bead@antibody served as the capture probes. Target materials were captured by probes and combined with SERS tags, forming a “sandwich” composite structure for subsequent detection.Results: Under optimized conditions, the nanocomposite fabricated could be used to detect simultaneously for insulin and C-peptide with the detection limit of 4.29 × 10− 5 pM and 1.76 × 10− 10 nM in serum. The insulin concentration (4.29 × 10− 5– 4.29 pM) showed a strong linear correlation with the SERS intensity at 1075 cm− 1, with high recoveries (96.4– 105.3%) and low RSD (0.8%– 10.0%) in detecting human serum samples. Meanwhile, the C-peptide concentration (1.76 × 10− 10– 1.76 × 10− 3 nM) also showed a specific linear correlation with the SERS intensity at 1333 cm− 1, with recoveries 85.4%– 105.0% and RSD 1.7%– 10.8%.Conclusion: This breakthrough provided a novel, sensitive, convenient and stable approach for clinical diagnosis of diabetes and certain liver diseases. Overall, our findings presented a significant contribution to the field of biomedical research, opening up new possibilities for improved diagnosis and monitoring of diabetes and liver diseases.Keywords: surface-enhanced Raman scattering, SERS, nanocomposites, insulin, C-peptide

Jing Wang,1 Wenyue Gao,1 Hongbo Yu,1 Yuting Xu,1 Changchuan Bai,2 Qingwei Cong,1 Ying Zhu1 1Infectious Department, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116000, People’s Republic of China; 2Internal Department of Chinese Medicine, Dalian Hospital of Traditional Chinese Medicine, Dalian, Liaoning, 116013, People’s Republic of ChinaCorrespondence: Ying Zhu, Email zhuyingsh52@126.comAbstract: Hepatocellular carcinoma (HCC) stands as the prevailing form of primary liver cancer, characterized by a poor prognosis and high mortality rate. A pivotal factor in HCC tumorigenesis is epigenetics, specifically the regulation of gene expression through methylation. This process relies significantly on the action of proteins that modify methylation, including methyltransferases, their associated binding proteins, and demethylases. These proteins are crucial regulators, orchestrating the methylation process by regulating enzymes and their corresponding binding proteins. This orchestration facilitates the reading, binding, detection, and catalysis of gene methylation sites. Methylation ences the development, prolisignificantly influferation, invasion, and prognosis of HCC. Furthermore, methylation modification and its regulatory mechanisms activate distinct biological characteristics in HCC cancer stem cells, such as inducing cancer-like differentiation of stem cells. They also influence the tumor microenvironment (TME) in HCC, modulate immune responses, affect chemotherapy resistance in HCC patients, and contribute to HCC progression through signaling pathway feedback. Given the essential role of methylation in genetic information, it holds promise as a potential tool for the early detection of HCC and as a target to improve drug resistance and promote apoptosis in HCC cells.Keywords: methylation modifying proteins, biomarkers, methyltransferases, HCC tumorigenesis

Jiawen Zhang,1,&ast; Duoduo Gu,2,&ast; Yang Yan,3,&ast; Ruoxin Pan,2 Hui Zhong,4,5 Chengfeng Zhang,1 Yang Xu2 1Department of Dermatology, Huashan Hospital of Fudan University, Shanghai, People’s Republic of China; 2Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Cardiology, Ren Ji Hospital of Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, People’s Republic of China; 5School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengfeng Zhang; Yang Xu, Email e3dangdang@hotmail.com; yangxu@njmu.edu.cnAbstract: Rosacea is a chronic inflammatory skin disease that affects a patient’s appearance and quality of life. It mainly affects the midface region and presents as erythema, flushing, telangiectasia, papules, pustules, and rhinophyma. Despite its prevalence, the precise pathophysiology of rosacea remains unknown, and novel pharmacological therapies are currently under investigation. Tranexamic acid (TA) is a synthetic, lysine-like compound that competitively inhibits fibrinogen production by synthesizing fibrinolytic enzymes. In addition to its popular application in hemorrhage treatment, TA has been used to manage a number of skin conditions, including melasma, chronic urticaria, and angioedema. TA is a better option for melasma treatment. However, the role of TA in treating rosacea has not yet been systematically elucidated. In this study, we reviewed all available literature on the use of TA for rosacea treatment. The included articles examined the therapeutic effects of TA in patients with rosacea, including traditional methods such as oral and topical administration and more novel approaches such as intradermal injections, microneedling, and laser-assisted delivery. Several recent clinical studies demonstrated that TA alleviates rosacea symptoms by restoring the permeability barrier, ameliorating the immune reaction, and inhibiting angiogenesis. In this review, we summarized the function and potential application of TA in rosacea treatment, aiming to facilitate the implementation of clinical applications.Keywords: rosacea, tranexamic acid, topical, oral, microinjection

Li Zhang,1,&ast; Menglan Zhou,2,3,&ast; Ziran Wang,2,3,&ast; Hongqiong Zhu,4 Jing Lin,1,5 Minya Lu,2,3 Ying Ge,1 Yingchun Xu,2,3 Taisheng Li,1 Zhengyin Liu1 1Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 4Department of Infectious Disease, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 5Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengyin Liu, Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Number 1, Shuaifuyuan Road, Dongcheng District, Beijing, People’s Republic of China, Email zhengyinl@hotmail.comBackground: In China, due to the large population, infections caused by Nocardia may not be as rare. Unfortunately, there is still inadequate knowledge of the clinical impact caused by Nocardia. This study aimed to compare the clinical characteristics and treatment of localized and disseminated nocardiosis.Methods: The clinical and microbiological data of patients diagnosed with nocardiosis in a tertiary hospital in Beijing from July 2011 to July 2021 were collected and retrospectively analyzed.Results: Among the 54 nocardiosis cases, 34 cases were in the localized infection group, while 20 cases in the disseminated infection group. The proportion of patients with chronic structural lung disease was higher in the localized group (P=0.010). In contrast, patients with disseminated infections were more prone to receive long-term glucocorticoids and/or immunosuppressants (P=0.027). Pulmonary nodules were prominent features of imaging changes in patients with disseminated infections (P=0.027) whereas bronchial dilatation was more common in patients with localized infections (P=0.025). In addition, the disseminated group had longer average hospitalization days relative to the localized group (P=0.016), but there was no significant difference in mortality between them (P=0.942).Conclusion: There were differences in the clinical profiles between patients with localized and disseminated nocardiosis in terms of clinical presentation, infection site, radiological features, treatment, and prognosis. These findings may provide references for the management and treatment of patients with nocardiosis.Keywords: Nocardia, disseminated nocardiosis, immunosuppressive population

Ying Wang,1,&ast; Yiyan Xu,2,&ast; Jiayu Song,1 Xueting Liu,1 Sijia Liu,1 Nan Yang,1 Le Wang,1 Yujie Liu,1 Yiwei Zhao,1 Wenhu Zhou,3,4 Yunyan Zhang1 1Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Department of Vascular Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, People’s Republic of China; 3Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 4Hunan Key Laboratory of The Research and Development of Novel Pharmaceutical Preparations, School of Pharmaceutical Science, Changsha Medical University, Changsha, 410219, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunyan Zhang, Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang Province, 150081, People’s Republic of China, Tel +86 13604843878, Fax +86 451 85718392, Email zhangyunyan@hrbmu.edu.cn Wenhu Zhou, Xiangya School of Pharmaceutical Sciences, Central South University, 172 Tongzipo Road, Changsha, Hunan, 410013, People’s Republic of China, Tel +86 15111469284, Fax +86 731 88710591, Email zhouwenhuyaoji@163.comPurpose: Phototherapy, known for its high selectivity, few side effects, strong controllability, and synergistic enhancement of combined treatments, is widely used in treating diseases like cervical cancer.Methods: In this study, hollow mesoporous manganese dioxide was used as a carrier to construct positively charged, poly(allylamine hydrochloride)–modified nanoparticles (NPs). The NP was efficiently loaded with the photosensitizer indocyanine green (ICG) via the addition of hydrogen phosphate ions to produce a counterion aggregation effect. HeLa cell membrane encapsulation was performed to achieve the final M-HMnO2@ICG NP. In this structure, the HMnO2 carrier responsively degrades to release ICG in the tumor microenvironment, self-generates O2 for sensitization to ICG-mediated photodynamic therapy (PDT), and consumes GSH to expand the oxidative stress therapeutic effect [chemodynamic therapy (CDT) + PDT]. The ICG accumulated in tumor tissues exerts a synergistic PDT/photothermal therapy (PTT) effect through single laser irradiation, improving efficiency and reducing side effects. The cell membrane encapsulation increases nanomedicine accumulation in tumor tissues and confers an immune evasion ability. In addition, high local temperatures induced by PTT can enhance CDT. These properties of the NP enable full achievement of PTT/PDT/CDT and targeted effects.Results: Mn2+ can serve as a magnetic resonance imaging agent to guide therapy, and ICG can be used for photothermal and fluorescence imaging. After its intravenous injection, M-HMnO2@ICG accumulated effectively at mouse tumor sites; the optimal timing of in-vivo laser treatment could be verified by near-infrared fluorescence, magnetic resonance, and photothermal imaging. The M-HMnO2@ICG NPs had the best antitumor effects among treatment groups under near-infrared light conditions, and showed good biocompatibility.Conclusion: In this study, we designed a nano-biomimetic delivery system that improves hypoxia, responds to the tumor microenvironment, and efficiently loads ICG. It provides a new economical and convenient strategy for synergistic phototherapy and CDT for cervical cancer.Keywords: phototherapy, reactive oxygen species, hypoxia relief, collaborative therapy

Yongzhi Xu,1,2,&ast; Yuanping Hao,2,&ast; Muhammad Arif,3 Xiaodong Xing,4 Xuyang Deng,1 Danyang Wang,1 Yang Meng,2 Shuai Wang,1 Mohamed Sayed Hasanin,5 Wanchun Wang,2 Qihui Zhou3,6 1School of Stomatology, Qingdao University, Qingdao, People’s Republic of China; 2Department of Stomatology, Qingdao Stomatological Hospital Affiliated to Qingdao University, Qingdao, People’s Republic of China; 3Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, People’s Republic of China; 4School of Chemical Engineering, Nanjing University of Science and Technology, Nanjing, People’s Republic of China; 5Cellulose and Paper Department, National Research Centre, Dokki, Cairo, Egypt; 6Hubei Key Laboratory of Biomass Fibers and Eco-Dyeing & Finishing, Wuhan Textile University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wanchun Wang; Qihui Zhou, Email kqwwch@126.com; qihuizhou@uor.edu.cnIntroduction: Persistent endodontic infections (PEIs) mediated by bacterial biofilm mainly cause persistent periapical inflammation, resulting in recurrent periapical abscesses and progressive bone destruction. However, conventional root canal disinfectants are highly damaging to the tooth and periodontal tissue and ineffective in treating persistent root canal infections. Antimicrobial materials that are biocompatible with apical tissues and can eliminate PEIs-associated bacteria are urgently needed.Methods: Here, &epsiv;-poly (L-lysine) derived carbon quantum dots (PL-CQDs) are fabricated using pyrolysis to remove PEIs-associated bacterial biofilms.Results: Due to their ultra-small size, high positive charge, and active reactive oxygen species (ROS) generation capacity, PL-CQDs exhibit highly effective antibacterial activity against Enterococcus faecalis (E. faecalis), which is greatly dependent on PL-CQDs concentrations. 100 μg/mL PL-CQDs could kill E. faecalis in 5 min. Importantly, PL-CQDs effectively achieved a reduction of biofilms in the isolated teeth model, disrupting the dense structure of biofilms. PL-CQDs have acceptable cytocompatibility and hemocompatibility in vitro and good biosafety in vivo.Discussion: Thus, PL-CQDs provide a new strategy for treating E. faecalis-associated PEIs. Keywords: carbon quantum dots, Enterococcus faecalis, bacterial biofilm, persistent endodontic infections

Pan Gao,1,&ast; Xinyu Li,1,&ast; Ziqiu He,1 Yifan Xu,2 Zhi Zhang1 1Department of Urology, Second People’s Hospital of Yichang, Second People’s Hospital of China Three Gorges University, Yichang, Hubei Province, People’s Republic of China; 2Department of Pathology, Second People’s Hospital of Yichang, Second People’s Hospital of China Three Gorges University, Yichang, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi Zhang, Department of Urology, Second People’s Hospital of Yichang, Second People’s Hospital of China Three Gorges University, 21 Xiling One Road, Yichang, Hubei Province, 443000, People’s Republic of China, Email 702032715@qq.comAbstract: Primary bladder large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive neoplasm with high recurrence rates and poor prognosis. Traditional management has heavily relied on radical cystectomy, which, despite its aggressiveness, often results in unsatisfactory outcomes. Emerging evidence suggests the potential for less invasive, bladder-sparing approaches, yet detailed reports and long-term outcomes remain scarce. We report a groundbreaking case of a 59-year-old male diagnosed with primary bladder LCNEC, managed through a pioneering bladder-sparing multimodal treatment. This novel strategy included transurethral resection followed by a tailored chemoradiation protocol, resulting in exceptional disease control and preservation of bladder function over a 20-month follow-up period, without evidence of recurrence. This case underscores the viability of bladder conservation strategies as a legitimate alternative to radical cystectomy for managing LCNEC, presenting a beacon of hope for patients wishing to preserve bladder functionality. It prompts a reevaluation of traditional treatment paradigms and advocates for further research into multimodal, organ-sparing approaches for this challenging malignancy.Keywords: LCNEC, bladder conservation, TURBT, secondary transurethral resection, EP regimen, radiotherapy