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Chen Zhao, Dan Wang, Junxiao Zhang, Shaowen Ge, Zhaojun Zhan, Li Xu, Shengkai Liao Department of Stomatology, First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, People’s Republic of ChinaCorrespondence: Li Xu; Shengkai Liao, Department of Stomatology, First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, People’s Republic of China, Email kqxuli@163.com; lsk3166@163.comBackground and Purpose: Periodontitis is the leading cause of tooth loss in adults worldwide. The functional loss, nutritional deficiencies, and psychological barriers it causes, as well as its impact on overall health and quality of life, are all significant. The prevalence of periodontal disease is high in China. Our study aimed to determine the intricate relationship between periodontal disease status, dental anxiety, self-rated oral health (SROH), self-efficacy for oral care, perceived social support, socioeconomic status (SES), and the oral health-related quality of life (OHRQoL) among periodontitis patients.Methods: This cross-sectional study used purposive sampling to identify 247 patients with periodontitis who entered the First Affiliated Hospital of Bengbu Medical University between October 2022 and October 2023. 247 participants underwent a periodontal clinical examination combined with imaging, adhering to the “ 2018 world new classification of periodontal and peri⁃implant diseases and conditions”. Participants also completed a detailed questionnaire in paper format, which included OHRQoL, sociodemographic details, dental anxiety, SROH, self-efficacy in oral care, perceived social support, and subjective SES.Results: Dental anxiety, self-efficacy for oral care, and SROH all had a direct and significant effect on OHRQoL. OHRQoL was indirectly related to SROH mediated by dental anxiety and subjective SES, perceived social support and self-efficacy for oral care, respectively. SROH was directly related to subjective SES, and at the same time, they had a direct effect on dental anxiety. Furthermore, patient’s age, gender, annual household income, and education level were significantly associated with the degree of periodontal disease.Conclusion: OHRQoL and periodontal status was influenced by socio-demographics characteristics, dental anxiety, SROH, self-efficacy for oral care, perceived social support, subjective SES in periodontitis patients. These insights underscore the importance of adopting a holistic approach in the management and treatment of periodontal diseases.Keywords: periodontitis, oral health-related quality of life, self-rated oral health, structural equation modeling

Mingyue Shang,* Zhehong Li,* Guangzhong Xu, Dongbo Lian, Zhaohui Liao, Dezhong Wang, Buhe Amin, Zheng Wang, Weijian Chen, Dexiao Du, Nengwei Zhang, Liang Wang Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, 100038, People’s Republic of China*These authors contributed equally to this workCorrespondence: Nengwei Zhang; Liang Wang, Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, No. 10, Tieyi Road, Yangfangdian, Haidian District, Beijing, 100038, People’s Republic of China, Tel +8613801068802 ; +8619800320171, Email zhangnw@ccmu.edu.cn; 1911110644@pku.edu.cnPurpose: Gastroesophageal reflux disease (GERD) is a common complication after laparoscopic sleeve gastrectomy (LSG); This study aimed to construct a model that can predict the incidence of GERD after LSG by exploring the correlation between the results of high-resolution esophageal manometry (HREM) and the incidence of GERD after LSG.Patients and Methods: We collected the clinical data of patients who had undergone HREM before bariatric surgery from September 2013 to September 2019 at the bariatric center of our hospital. The Gerd-Q scores during the postoperative follow-up were collected to determine the incidence of GERD. A logistic regression analysis was performed to explore the correlation of the HREM results and general clinical data with the incidence of GERD after LSG.Results: The percentage of synchronous contractions, lower esophageal sphincter (LES) resting pressure, and history of smoking were correlated with the development of GERD after LSG, with the history of smoking and percentage of synchronous contractions as risk factors and LES resting pressure as a protective factor. The training set showed an area under the ROC curve (AUC) of the nomogram model of 0.847. The validation set showed an AUC of 0.761. The decision and clinical impact curves showed a high clinical value for the prediction model.Conclusion: The HREM results correlated with the development of GERD after LSG, with the percentage of synchronous contractions and LES resting pressure showing predictive value. Combined with the history of smoking, the predictive model showed a high confidence and clinical value.Keywords: gastroesophageal reflux disease, laparoscopic sleeve gastrectomy, high-resolution esophageal manometry, complications

Dandan Wang,1– 3,* Jingguo Wang,3,* Zequn Yin,4 Ke Gong,3 Shuang Zhang,3 Zhengbao Zha,3 Yajun Duan4 1School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, 230011, People’s Republic of China; 2State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, People’s Republic of China; 3School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, 230601, People’s Republic of China; 4Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhengbao Zha, School of Food and Biological Engineering, Hefei University of Technology, No. 420 Feicui Road, Hefei, Anhui, 230601, People’s Republic of China, Email zbzha@hfut.edu.cn Yajun Duan, Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No. 96 Jinzhai Road, Hefei, Anhui, 230031, People’s Republic of China, Email yajunduan@ustc.edu.cnIntroduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver disorder, has garnered increasing attention globally owing to its associated health complications. However, the lack of available therapeutic medications and inadequate management of complications in metabolic dysfunction-associated steatohepatitis (MASH) present significant challenges. There are little studies evaluating the effectiveness of POM in treating MASLD. In this study, we synthesized polyoxometalates (POM) for potential treatment of MASLD.Methods: We induced liver disease in mice using two approaches: feeding a high-fat diet (HFD) to establish MASLD or feeding a methionine–choline deficient (MCD) diet to induce hepatic lipotoxicity and MASH. Various metabolic parameters were detected, and biochemical and histological evaluations were conducted on MASLD. Western blotting, qRT-PCR and immunofluorescence assays were used to elucidate the molecular mechanism of POM in the treatment of MASLD.Results: POM therapy resulted in significant improvements in weight gain, dyslipidemia, liver injury, and hepatic steatosis in mice fed a HFD. Notably, in a more severe dietary-induced MASH model with MCD diet, POM significantly attenuated hepatic lipid accumulation, inflammation, and fibrosis. POM treatment effectively attenuated palmitic acid and oleic acid-induced lipid accumulation in HepG2 and Huh7 cells by targeting the AMPK pathway to regulate lipid metabolism, which was confirmed by AMPK inhibitor. Additionally, the activation of AMPK signaling by POM suppressed the expression of lipid synthesis genes, including sterol regulatory element-binding protein 1c (SREBP1c) and SREBP2, while concurrently upregulating the expression of sirtuin 1 (SIRT1) to promote fatty acid oxidation.Conclusion: These findings suggest that POM is a promising therapeutic strategy with high efficacy in multiple MASLD models. Keywords: polyoxometalates, MASLD, MASH, AMPK, lipotoxicity

Runing Fu,1,* Wenping Lian,1,* Bohao Zhang,2,* Gang Liu,3 Xinyu Feng,1 Yingjie Zhu,1 Jiuan Zhou,1 Xinyu Zhang,4 Shukai Wang,1 Huijuan Huo,1 Daxin Wang,1 Cui Liu,1 Saisai Gao,1 Yajie Ma,4 Mengle Peng1,* 1Department of Clinical Laboratory, The Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China; 2Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, People’s Republic of China; 3The Center of Meige Syndrome, The Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China; 4Department of Medical Affair, the Third People’s Hospital of Henan Province, Zhengzhou, Henan, 450006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mengle Peng; Yajie Ma, Email pengmengle1990@126.com; szsyywk@sina.comPurpose: Inflammatory markers are known to be associated with many diseases, but their role in Meige syndrome (MS) remains unclear. This study aimed to develop and validate a nomogram for the risk prediction of MS based on inflammatory markers.Patient Data and Methods: Data from 448 consecutive patients with MS at the Third People’s Hospital of Henan Province between January 2022 and December 2023 were retrospectively reviewed. The MS cohort was randomly divided into separate training and validation sets. A nomogram was constructed using a multivariate logistic regression model based on data from the training set. The model’s performance was validated through cross-validation, receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA).Results: A total of five predictors, including red blood cell distribution width (RDW), hemoglobin (HGB), high-density lipoprotein cholesterol (HDL-C), the lymphocyte-to-monocyte ratio (LMR), and the systemic immune‐inflammation index (SII), were identified using multivariate logistic regression from a total of 11 variables. The cross-validation results indicated the stability of the model constructed with the above five predictors. The model showed moderate predictive ability, with an area under the ROC curve of 0.767 in the training set and 0.735 in the validation set. The calibration curve and DCA results indicate that the model has strong consistency and significant potential for clinical application.Conclusion: We constructed a nomogram based on five risk predictors, RDW, HGB, HDL-C, the LMR and the SII, to predict MS and enhance the predictive accuracy for identifying MS risk.Keywords: Meige syndrome, inflammatory marker, nomogram, LMR, SII

Hui Li,1 Dan Wang2 1Department of Rehabilitation, Chongqing Jiangbei Hospital of Traditional Chinese Medicine, Chongqing, People’s Republic of China; 2Traditional Chinese Medicine College, Hubei University of Chinese Medicine, Wuhan, People’s Republic of ChinaCorrespondence: Dan Wang, Traditional Chinese medicine college, Hubei University of Chinese Medicine, #16 huangjiahu West Road, Wuhan, People’s Republic of China, Tel +86-27-85332102, Email Wangdan_19950203@126.comAbstract: Insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) are representative metabolic diseases, and no pharmacological therapeutic strategies have been developed worldwide. In recent studies, acupuncture has increasingly been used as an integrative or complementary therapy for IR and NAFLD. In this review, we summarized 18 clinical trials and 25 animal studies to reveal the function and potential molecular mechanisms of acupuncture for IR and NAFLD treatment. We found that acupuncture can be a first-line treatment strategy for IR and has a positive therapeutic effect on NAFLD. Thus, this review provides clinicians with a deeper understanding of the scientific evidence for acupuncture treatment of IR and NAFLD. Finally, we highlighted three potential limitations of existing studies on acupuncture for the treatment of IR and NAFLD, including small sample sizes and inconsistent operating techniques.Keywords: Traditional Chinese Medicine, acupuncture, insulin resistance, non-alcoholic fatty liver disease, metabolic health, alternative therapy

Dan Wang,1,2,* Jing-Hui Hu,1,2,* Hai-Jing Shi,1,2,* Min-Yuan Zhuang,1,2 Wei Dou,1,2 Fu-Hai Ji,1,2 Ke Peng1,2 1Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Institute of Anesthesiology, Soochow University, Suzhou, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ke Peng, Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-512-67780055, Email pengke0422@163.comBackground: Emergence agitation (EA) is a state of psychomotor hyperactivity following general anesthesia and is associated with postoperative complications. Patients undergoing ear, nose, and throat (ENT) surgery are at a high risk for EA. We aim to assess whether preoperative dexmedetomidine nasal spray reduces the occurrence of EA for patients undergoing ENT surgery.Methods: This is a protocol for a randomized, double-blind, controlled trial that will include 160 adults scheduled for ENT surgery. Patients will be randomly assigned, in a 1:1 ratio, to receive dexmedetomidine nasal spray (100 μg) or a same volume of normal saline approximately 30 min before general anesthesia induction. The primary endpoint is the incidence of EA, defined as a Riker sedation agitation scale (RSAS) score ≥ 5 from discontinuation of sevoflurane until 5 min after tracheal extubation. Secondary endpoints include (1) the maximal RSAS score during emergence; (2) the incidence of agitation in the postoperative care unit (PACU); (3) pain at rest and while coughing in the PACU and at 24 h postoperatively; (4) postoperative sleep disturbance on the first night after surgery; (5) anxiety within 24 h postoperatively; and (6) postoperative delirium during the first 24 h after surgery. All analyses will be performed on a modified intention-to-treat basis. For the primary endpoint, subgroup analysis will be conducted on sex, age, and type of surgery.Discussion: We expect that preoperative dexmedetomidine nasal spray would reduce the incidence of EA after ENT surgery. Our results offer clinical evidence for improving anesthetic care for patients undergoing ENT surgery.Trial Registration: Chinese Clinical Trial Registry (Identifier: ChiCTR2400086731).Keywords: emergence agitation, dexmedetomidine, intranasal administration, ENT surgery

Xinyang Nie,1– 3,* Jian Liu,1,2,* Daohan Wang,1,2,* Chuan Li,1,2 Yuxin Teng,1,2 Zhufeng Li,1,2 Yangpu Jia,1,2 Peiyao Wang,1,2 Jingyu Deng,2,3 Weidong Li,1,2 Li Lu1,2 1Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Lu; Weidong Li, Department of General surgery, Tianjin Medical University General Hospital, 154, Anshan Road, Heping District, Tianjin, 300052, People’s Republic of China, Email luli_1989@126.com; tjmughgs_lwd@163.comBackground: Cisplatin (DDP) resistance in gastric cancer (GC) is likely to come from gastric cancer stem cells (GCSC). It is a new idea to study the mechanism of the DDP-resistance in GCSC from miRNA.Materials and Methods: CD44+ GCSCs and CD44- control cells were constructed based on the HGC27 gastric cancer cell line. DDP sensitivities in CD44+ and CD44- cells were detected via CCK-8 assay. The differential expression of miR-21-5p in these cell lines was detected by RT‒qPCR. The expression levels of downstream TGF-β 2, SMAD2 and SMAD3 were determined through RT‒PCR and Western blotting. A luciferase assay was used to detect the relationship between miR-21-5p and TGFB2, and the TCGA database, clinical data from our centre, and vivo experiment were used for validation. Finally, we knocked down miR-21-5p to detect changes in cisplatin resistance in GCSCs and to verify changes in the levels of downstream pathways in GCSCs.Results: CD44+ GCSCs induced cisplatin resistance compared with CD44- cells. miR-21-5p was highly expressed in GCSCs, and the TGF-β 2/SMAD pathway was also highly expressed. TGFB2 was proven to be a downstream target gene of miR-21-5p and had a positive relationship with it in phenotype. After knockdown of miR-21-5p, the TGF-β 2/SMAD pathway was also inhibited, and the resistance of GCSCs to cisplatin was specifically decreased.Conclusion: MiR-21-5p promotes cisplatin resistance in gastric cancer stem cells by regulating the TGF-β 2/SMAD signalling pathway.Keywords: miR-21-5p, cisplatin resistance, GCSCs, TGF-β 2 pathway

Weibei Sheng,1 Yaohang Yue,1 Tiantian Qi,1 Haotian Qin,1 Peng Liu,1 Deli Wang,1 Hui Zeng,2 Fei Yu1 1Department of Bone & Joint Surgery, National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, 518036, People’s Republic of China; 2Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, People’s Republic of ChinaCorrespondence: Hui Zeng; Fei Yu, Email zenghui_36@163.com; oscarfyu@163.comAbstract: Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the degradation of joint cartilage, subchondral bone sclerosis, synovitis, and structural changes in the joint. Recent research has highlighted the role of various genes in the pathogenesis and progression of OA, with nuclear factor erythroid 2-related factor 2 (NRF2) emerging as a critical player. NRF2, a vital transcription factor, plays a key role in regulating the OA microenvironment and slowing the disease’s progression. It modulates the expression of several antioxidant enzymes, such as Heme oxygenase-1 (HO-1) and NAD(P)H oxidoreductase 1 (NQO1), among others, which help reduce oxidative stress. Furthermore, NRF2 inhibits the nuclear factor kappa-B (NF-κB) signaling pathway, thereby decreasing inflammation, joint pain, and the breakdown of cartilage extracellular matrix, while also mitigating cell aging and death. This review discusses NRF2’s impact on oxidative stress, inflammation, cell aging, and various cell death modes (such as apoptosis, necroptosis, and ferroptosis) in OA-affected chondrocytes. The role of NRF2 in OA macrophages, and synovial fibroblasts was also discussed. It also covers NRF2’s role in preserving the cartilage extracellular matrix and alleviating joint pain. The purpose of this review is to provide a comprehensive understanding of NRF2’s protective mechanisms in OA, highlighting its potential as a therapeutic target and underscoring its significance in the development of novel treatment strategies for OA.Keywords: nuclear factor erythroid 2-related factor 2, osteoarthritis, chondrocytes, inflammation, oxidative stress

Jia Zhang,1 Zhijian Wang,1 Yushan Jiang,1 Dan Zhang,2 Wanyan Den,3 Danni Wang,1 Jiayi Peng,1 Jiajun Li,4,* Wenxiang Huang1,* 1Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Emergency and Critical Care, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Pathogenic Biology, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 4Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenxiang Huang, Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China, Email wenxiang_huang@163.comAbstract: Streptococcus pyogenes, also known as Group A Streptococcus (GAS), can cause severe invasive diseases with high fatality rates. We report a case of necrotizing fasciitis and myositis complicated by Streptococcal Toxic Shock-Like Syndrome (STSS) caused by the invasive emm 22/ST46 strain of Streptococcus pyogenes in China. A previously healthy 57-year-old Chinese Canadian man presented with right calf pain and ulceration following a hike in the Gobi Desert, which progressed to unconsciousness and severe infection. Despite initial treatment, his condition deteriorated, leading to his transfer to our intensive care unit. Metagenomic Next-Generation Sequencing identified Streptococcus pyogenes, and antimicrobial susceptibility testing revealed resistance to erythromycin, tetracycline, and clindamycin. Despite broad-spectrum antimicrobial therapy, debridement, and supportive measures, the patient’s condition necessitated amputation of the right lower limb. He recovered and was discharged from the hospital on Day 43. Whole-genome sequencing of the isolate identified 15 multiple virulence factors. Phylogenetic analysis revealed that the closest relative of the isolate was a strain identified in China. This case underscores the importance of early recognition and treatment of invasive GAS infections to prevent severe outcomes, and we should pay attention to invasive emm 22/ST46 GAS infections in China.Keywords: group A Streptococcus, streptococcal toxic shock-like syndrome, amputation, superantigens, metagenomic next-generation sequencing

Lin-Zhu Zhang,* Rui-Jie Du,* Duo Wang,* Juan Qin, Chao Yu, Lei Zhang, Hai-Dong Zhu Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Zhang; Hai-Dong Zhu, Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, People’s Republic of China, Email zhang_lei@seu.edu.cn; zhuhaidong@seu.edu.cnAbstract: With the in-depth knowledge of the pathological and physiological characteristics of the intestinal barrier–portal vein/intestinal lymphatic vessels–systemic circulation axis, oral targeted drug delivery is frequently being renewed. With many advantages, such as high safety, convenient administration, and good patient compliance, many researchers have begun to explore targeted drug delivery from intravenous injections to oral administration. Over the past few decades, the fields of materials science and nanomedicine have produced various drug delivery platforms that hold great potential in overcoming the multiple barriers associated with oral drug delivery. However, the oral transport of particles into the systemic circulation is extremely difficult due to immune rejection and biochemical invasion in the intestine, which limits absorption and entry into the bloodstream. The feasibility of the oral delivery of targeted drugs to sites outside the gastrointestinal tract (GIT) is unknown. This article reviews the biological barriers to drug absorption, the in vivo fate and transport mechanisms of drug carriers, the theoretical basis for oral administration, and the impact of carrier structural evolution on oral administration to achieve this goal. Finally, this article reviews the characteristics of different nano-delivery systems that can enhance the bioavailability of oral therapeutics and highlights their applications in the efficient creation of oral anticancer nanomedicines. Keywords: oral nanomedicine, oral targeted drug delivery, nanoparticles, cancer treatment, biological barriers

Jiahuan Guo,1 Dandan Wang,1 Jiaokun Jia,1 Jia Zhang,1 Yanfang Liu,1 Jingjing Lu,1,2 Xingquan Zhao,1– 4,&ast; Jing Yan1,&ast; 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Center of Stroke, Beijing Institute for Brain Disorders, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingquan Zhao; Jing Yan, Email zxq@vip.163.com; joyce_yj@163.comPurpose: Inflammatory response plays essential roles in the pathophysiology of both ischemic stroke and atrial fibrillation (AF). We aimed to investigate whether composite inflammatory markers, including neutrophil to lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR), can serve as early predictors of short- and long-term outcomes in ischemic stroke patients with AF.Patients and Methods: Ischemic stroke patients with AF were enrolled in this cohort study. The primary outcome was 1-year functional dependence or death (modified Rankin scale (mRS) score 3– 6). Secondary outcomes included hemorrhagic transformation (HT) and early neurological deterioration (END, increase in the National Institutes of Health Stroke Scale (NIHSS) ≥ 4 within 7 days). Partial correlations were performed to assess the correlation between systemic inflammation markers and admission NIHSS scores. Univariate and multivariate logistic analyses were performed to investigate whether systemic inflammatory markers were independent predictors of adverse outcomes.Results: A total of 408 patients were included. Partial correlation analysis revealed statistically significant but weak correlations between the NLR (r = 0.287; P < 0.001), PLR (r = 0.158; P = 0.001) and admission NIHSS score. Compared with patients without HT or END, patients who developed HT or END had higher NLR and PLR, and lower LMR. Patients in the functional dependence or death group had significantly higher NLR and PLR, and lower LMR than those in the functional independence group (all P < 0.001). Multivariate logistic analysis indicated that NLR, LMR and PLR were independent predictors of HT (OR = 1.069, 0.814 and 1.003, respectively), END (OR = 1.100, 0.768 and 1.006, respectively) and adverse 1-year functional outcome (OR = 1.139, 0.760 and 1.005, respectively).Conclusion: NLR, LMR and PLR were independent predictors for in-hospital HT, END and long-term functional outcome in ischemic stroke patients with AF. Close monitoring of these inflammatory markers may help guide risk stratification and clinical treatment strategies.Keywords: inflammation, ischemic stroke, atrial fibrillation, hemorrhagic transformation, early neurological deterioration, functional outcome

Mingyue Shang,&ast; Zhehong Li,&ast; Dexiao Du,&ast; Guangzhong Xu, Dongbo Lian, Zhaohui Liao, Dezhong Wang, Buhe Amin, Zheng Wang, Weijian Chen, Nengwei Zhang, Liang Wang Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, 100038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nengwei Zhang; Liang Wang, Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, No. 10, Tieyi Road, Yangfangdian, Haidian District, Beijing, 100038, People’s Republic of China, Tel +8613801068802 ; +8619800320171, Email zhangnw@ccmu.edu.cn; 1911110644@pku.edu.cnPurpose: Obesity and related complications are managed by One Anastomosis Gastric Bypass (OAGB) and Single Anastomosis Duodeno-Jejunal Bypass with Sleeve Gastrectomy (SADJB-SG), both of which are adapted from traditional gastric bypass procedures. However, there are no current comparative studies on the safety and efficacy of these two surgical procedures.Patients and Methods: Preoperative baseline data of patients who had undergone OAGB and SADJB-SG surgeries from June 2019 to June 2021 were retrospectively analyzed at our bariatric facility. Postoperative data, including weight changes, improvement in type 2 diabetes (T2DM), and complication rates were collected over 2 years. This was followed by a comprehensive evaluation of the safety and efficacy of the two surgical procedures.Results: A total of 63 patients completed the follow-up in this study. At the 24-month follow-up, excess weight loss percentage (EWL%) for the OAGB and SADJB-SG was 73.970± 5.005 and 75.652± 7.953, respectively (P-value = 0.310); total weight loss percentage (TWL%) was 24.006± 8.231 and 23.171± 6.600, respectively (P-value = 0.665). The diabetes remission rates for the two groups were 71.429% and 69.048%, respectively (P-value = 0.846). The cost for OAGB was 55088.208± 1508.220 yuan, which was significantly lower than the 57538.195± 1374.994 yuan for SADJB-SG (P-value< 0.001).Conclusion: The two surgical procedures are reliable in terms of safety and efficacy, and each has distinct advantages. While OAGB has reduced operational expenses, SADJB-SG offers a broader range of applicability.Keywords: one anastomosis gastric bypass, single anastomosis duodeno-jejunal bypass with sleeve gastrectomy, safety, efficacy

Jun Zhan,1,2 Dingding Wang,1,2 Chuanxiang Luo,3 Haiyan Bi4 1Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, People’s Republic of China; 3Department of Clinical Medicine, Medical College, Qingdao University, Qingdao, People’s Republic of China; 4Office for Medical and Health Service, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Haiyan Bi, Office for Medical and Health Service, West China Second University Hospital, Sichuan University, Email 649927649@qq.comAbstract: Umbilical vascular thromboembolism is a rare condition that can lead to serious consequences such as fetal hypoxia, fetal growth restriction, and even stillbirth. However, there is currently a lack of research on the pathology, pathogenesis, clinical management, and prognosis of this condition. Therefore, the purpose of this article is to analyze this condition’s high-risk factors, clinical characteristics, pregnancy management, and discuss its corresponding pregnancy outcomes. Databases such as PubMed are searched using the relevant keywords of umbilical vascular thromboembolism in worldwide. And related information is analyzed such as maternal risk factors, fetal risk factors, umbilical cord and placental risk factors, and pregnancy outcomes. The literature search yields 113 articles, 64 of which meet the inclusion criteria for umbilical vascular thromboembolism. There are 4 retrospective cohort studies and 8 case series, the rest are all case reports. A total of 262 cases of umbilical vascular thromboembolism are found. The most common maternal complications and fetal related risk factors are diabetes (25 cases, 9.5%) and stillbirths (106 cases, 40.5%), respectively. Among these 262 cases, 98 (37.4%) cases are found by prenatal ultrasound to have umbilical vascular thromboembolism and the fetus is in a viable state with complete clinical information. In addition, considering the effectiveness and safety of low molecular weight heparin in thromboembolic conditions, twenty-four patients of umbilical artery thromboembolism attempted to use low molecular weight heparin during observation. Maternal diabetes was the highest risk factor for this condition. When umbilical artery thromboembolism occurs, the incidence of stillbirth increases. Premature patients with this condition can continue their pregnancy under close external monitoring. However, due to the small sample size, further research is needed.Keywords: umbilical vascular thromboembolism, umbilical vein thromboembolism, umbilical artery thromboembolism, fetal growth restriction, umbilical vein varix, low molecular weight heparin

Dong Wang,&ast; Xinsheng Yan,&ast; Luo Yang, Litao Zhang Department of Clinical Laboratory, Wuhan Asia General Hospital, Wuhan Asia General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, 430056, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong Wang; Litao Zhang, Email wangdongwuhan001@163.com; whyxzyyzlt@163.comPurpose: Human papillomavirus (HPV) infection is a prevalent sexually transmitted infection worldwide, with its persistence being a significant factor in the development of cervical cancer and precancerous lesions. Understanding the prevalence and genotypes distribution of HPV can aid in the implementation of more focused strategies for cervical cancer prevention and treatment. This study aimed to investigate the prevalence and genotype distribution of HPV infection among outpatient-based populations in Wuhan, China.Methods: Our study retrospectively analyzed the results of cervical HPV screening in 14,492 outpatient women. The cervicovaginal infection of 18 high-risk genotypes and 10 low-risk genotypes were analyzed by PCR and reverse dot hybridization techniques.Results: The overall prevalence of HPV infection in the outpatient female population was 15.33%, with a predominance of single infection and a predominance of dual infection among multiple infections. The top five genotypes in terms of prevalence of HR-HPV and LR-HPV were HPV-52 (3.77%), 53 (1.46%), 16 (1.31%), 58 (1.19%), 39 (1.18%) for HR-HPV, and HPV-54 (1.23%), 61 (1.08%), 81 (1.04%), 42 (0.87%), 44 (0.70%) for LR-HPV. Two peaks of HPV infection prevalence were observed among women under 25 years (22.88%) and over 56 years (24.26%). The prevalence and genotype distribution of HPV infection varied among different outpatient populations, with higher rates of HPV single infection, multiple infections, and infection across all ages observed in the gynecology outpatient population compared to the health check-up population.Conclusion: This study revealed the HPV prevalence and genotype distribution among different outpatient populations in Wuhan city, which may provide guidance for HPV vaccination and cervical cancer prevention strategies in the region.Keywords: human papillomavirus, prevalence, genotype, high-risk HPV, low-risk HPV, cervical cancer

Mengcao Weng,1,&ast; Dongdong Wang,2,&ast; Jia Zhong,2 Minyue Qian,1 Kai Zhang,2 Yue Jin1 1Department of Anesthesiology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Anesthesiology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Jin, Department of Anesthesiology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, 3333 Binsheng Rd, Hangzhou, Zhejiang, 310052, People’s Republic of China, Tel +8613456912018, Email yue_jin@zju.edu.cn Kai Zhang, Department of Anesthesiology, the First Affiliated Hospital, Zhejiang University School of Medicine, Wenyixi Road 1367, Hangzhou, 311121, People’s Republic of China, Tel +8615858281107, Email comezk@zju.edu.cnPurpose: This study aimed to establish the 95% effective dose (ED95) of esketamine in combination with propofol for hysteroscopy and then to evaluate its efficacy and safety profile.Patients and Methods: This prospective, double-blind, randomized controlled trial consisted of two cohorts. In cohort 1, 45 women aged 18– 65 years undergoing hysteroscopy were randomly assigned to either group E (esketamine + propofol) or group A (alfentanil + propofol). Dixon’s up-and-down method was used to determine the ED95 of esketamine and alfentanil. In cohort 2, 86 patients were randomized to group E and group A, with the calculated ED95 dose of the study drugs used for induction. The success rate of anesthesia using the ED95% dose, along with parameters related to anesthesia induction, recovery, and adverse events were also recorded.Results: The ED95 of esketamine was 0.254 mg/kg (95% CI: 0.214– 1.004), while that of alfentanil was 9.121 μg/kg (95% CI: 8.479– 13.364). The anesthesia success rate was 93.0% in group E and 95.2% in group A (p = 0.664). After resuscitation, both groups achieved a 100% success rate. The induction time was significantly shorter in group E (60.0 [55.0– 70.0] s) compared to group A (67.0 [61.0– 79.3] s) (p = 0.006). Group E had lower rates of respiratory depression (p < 0.001), hypoxia (p = 0.006), minimum perioperative SpO2 (p = 0.010), and hypotension (p = 0.001). Esketamine had less effect on respiratory rate, heart rate, mean blood pressure, and end-tidal carbon dioxide compared to alfentanil (all p < 0.001). There were no significant differences in postoperative pain between the two groups.Conclusion: This study determined the ED 95 dose of esketamine for intravenous general anesthesia during hysteroscopy. Esketamine showed less respiratory and hemodynamic depression, as well as fewer adverse effects compared to alfentanil. Esketamine is an ideal anesthetic agent compared to alfentanil for hysteroscopic anesthesia.Trial Registration: www.chictr.org.cn, (ChiCTR2300077283); registered November 3, 2023.Keywords: esketamine, 95% effective dose, hysteroscopy, propofol

PingPing Jiang,1,&ast; JingTao Tang,2,&ast; Min Zhang,3 Dan Wang1 1Department of Anesthesia, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 2Department of Anesthesia, The Second People’s hospital of Neijiang, Neijiang, Sichuan, People’s Republic of China; 3Department of Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: PingPing Jiang, Department of Anesthesia, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China, Tel +86 15881496034, Email 307174907@qq.comPurpose: This study aimed to observe the effect of bilateral transverse abdominis plane (TAP) block on the MACBAR of sevoflurane in gynecological patients with laparoscopic pneumoperitoneal stimulation.Patients and Methods: Fifty patients who underwent laparoscopic surgery were randomly assigned to either the control group (n= 25) or the TAP block group (n= 25). Patients in the TAP block group were subjected to a bilateral transversal abdominal muscle plane block with 0.33% ropivacaine (20 mL on each side) guided by ultrasound. The control group received an equal volume of normal saline. The MACBAR of sevoflurane in each group was determined using a sequential allocation technique.Results: The MACBAR of sevoflurane in the TAP block group was significantly lower than that in the control group (4.20% [95% confidence interval {CI}, 4.02%– 4.38%] vs 5.03% [95% CI, 4.89%– 5.18%]).Conclusion: Bilateral TAP block can reduce the MACBAR of sevoflurane in gynecological patients with pneumoperitoneum stimulation.Trial Registration Number: ChiCTR2100046517. The trial is publicly available and registered at www.chictr.org.cn on May 18, 2021.Keywords: Transverse abdominis plane block, Adrenergic response, Minimum alveolar concentration, Pneumoperitoneum stimulation, Sevoflurane

Fulin Tao,1,&ast; Lin Li,2,3,&ast; Dawei Wang,1,2 Jinlei Dong,1 Dongsheng Zhou,1,2 Wenhao Song1,2,4 1Department of Orthopedic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 2Department of Orthopedic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 3Department of Orthopedic Surgery, Tengzhou Central People’s Hospital Affiliated to Jining Medical University, Tengzhou, Shandong, People’s Republic of China; 4Shandong Yuhuang Chemical Co., Ltd, Heze, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenhao Song, Department of Orthopedic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China, Email songwenhao0308@163.comIntroduction: This study aimed to compare the efficacy of three methods for isolated greater tuberosity fractures of the humerus.Methods: A retrospective review of patients with isolated humeral greater tuberosity fractures between January 2013 and June 2021 in our institution. We recorded data on patient demographics, injury characteristics, preoperative and postoperative imaging findings, length of incision, operative time, and intraoperative blood loss.Results: A total of 107 patients met the inclusion criteria and were divided into three groups. 50 patients in group A were administered a proximal humeral internal locking system (PHILOS) plate fixed using the deltopectoral approach, 26 patients in group B were administered a PHILOS plate fixed using the deltoid-splitting approach, and 31 patients in group C were administered a novel anatomical plate fixed using the deltoid-splitting approach. No significant differences were identified in sex, age, injury mechanism, type of fracture, dominant side limb, or shoulder anterior joint dislocation. However, the operative time, blood loss, and the length of incision was shorter than in Group C. Moreover, pain was evaluated on the third and fifth days after surgery; pain was lower in Group C, and pain at the last follow-up was not different between the groups. No significant differences were identified in the Constant score, DASH score, and ROM at the last follow-up. 2 patients were diagnosed with subacromial impingement, 1 in Group A one in Group B, and 1 patient in Group B experienced axillary nerve injury after surgery.Conclusion: The novel anatomical plate fixed using the deltoid-splitting approach can achieve good results in the treatment of isolated humeral greater tubercle fractures with less blood loss, shorter operative time, and shorter surgical incisions, and can relieve pain in the early postoperative period.Keywords: PHILOS plate, a novel anatomical plate, deltopectoral approach, deltoid-splitting approach, greater tuberosity fracture of humerus

Zijuan Ma,1,&ast; Yunge Fan,1,&ast; Zhijun Yu,1 Wenxuan Wu,1 Xiangting Zhang,1 Huolian Li,1 Shaochen Zhao,2 Yang Li,3 Yuanyuan Li,4 Dongfang Wang,1 Fang Fan1 1Center for Studies of Psychological Application, School of Psychology, and Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, People’s Republic of China; 2Research Center for Guangdong-Hong Kong-Macao Policing Model Innovation, China People’s Police University, Guangzhou, People’s Republic of China; 3Department of Educational Psychology, Faculty of Education, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 4Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongfang Wang; Fang Fan, School of Psychology, South China Normal University, Shipai Road, Guangzhou, 510631, People’s Republic of China, Email wdfpsyc@126.com; fangfan@scnu.edu.cnPurpose: Although experimental psychopathology using PET, EEG, and fMRI is at the forefront of understanding the underlying mechanisms of sleep inertia, many questions concerning causality remain unanswerable due to ethical constraints and the use of small and heterogeneous samples in experimental methods. There is a pressing need for a novel perspective in a large and relatively homogeneous population to fully capture and elucidate longitudinal processes and dynamic causality that culminate in episodes of sleep inertia over time. Therefore, this study aimed to reveal the causal relationships between symptoms of sleep inertia across its distinct patterns.Patients and Methods: A total of 1636 intern nurses participated in the first survey (94.1% validity rate), then 1277 intern nurses were followed up (82.9% tracing rate). Symptoms of sleep inertia were self-reported using the Sleep Inertia Questionnaire. The cross-lagged panel network models were used to examine unique longitudinal relationships between symptoms of sleep inertia across distinct trajectories.Results: Four distinct trajectories of sleep inertia were established. Additionally, we found differences in those symptoms with the highest influence on other symptoms at the subsequent point across the networks of four trajectories, particularly, “Difficulty in concentrating” in the persistent-high group and “Feeling tense” in the deteriorating groups.Conclusion: The current study highlights changes in sleep inertia based on the long-term course over time. Notably, symptoms of “Difficulty in concentrating” and “Feeling tense” are imperative to address these specific symptoms within subpopulations.Keywords: sleep inertia, change patterns, network structures, intern nurse, shift work

Yantao Yu,1– 3,&ast; Chenkai Zhang,2,3,&ast; Qiannan Sun,2– 4 Shantanu Baral,2,3 Jianyue Ding,2,3 Fanyu Zhao,2,3 Qing Yao,2,3 Shuyang Gao,2,3 Bin Liu,2– 4 Daorong Wang1– 4 1The Yangzhou School of Clinical Medicine of Dalian Medical University, Yangzhou, 225001, People’s Republic of China; 2General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou, 225001, People’s Republic of China; 3Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou, 225001, People’s Republic of China; 4Northern Jiangsu People’s Hospital, Yangzhou, 225001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daorong Wang; Bin Liu, Email 18051062590@yzu.edu.cn; liubin2006cool@126.comBackground: Gastric cancer (GC) is a highly phenotypically heterogeneous disease and is caused by a combination of factors. Retinol binding protein 4 (RBP4) is a member of a family of lipid transport proteins that are involved in the transport of substances between cells and play a crucial role in a variety of cancers. However, the expression and role of RBP4 in GC remain unknown.Methods: In this study, we explored the expression, prognostic significance, immune microenvironment, drug responsiveness and function of associated signaling pathways of RBP4 in GC using web-based bioinformatics tools. Immunohistochemistry and real-time quantitative PCR were utilized to analyze the tissue and cell expression levels of RBP4. CCK-8, colony formation, EDU incorporation, wound healing and transwell assays were applied to demonstrate the effect of RBP4 on GC cell function. Flow cytometric detection of apoptosis after RBP4 knockdown. Nude mice xenograft model elucidates the role of RBP4 for GC in vivo. Related proteins of the RAS signaling pathway were analyzed by employing Western blot assays.Results: RBP4 is highly expressed in GC. RBP4 is closely associated with patient survival and sensitivity to a wide range of antitumor agents. Knockdown of RBP4 promoted apoptosis and inhibited cell proliferation, invasion and migration. RBP4 promotes GC tumorigenesis in vivo. Finally, RBP4 modulates the RAS/RAF/ERK axis.Conclusion: RBP4 may promote gastric carcinogenesis and development through the RAS/RAF/ERK axis and is expected to be a novel target for GC treatment.Keywords: RBP4, gastric cancer, invasion, migration, RAS/RAF/ERK axis

Siyang Cao,1– 3,&ast; Yihao Wei,1– 3,&ast; Yaohang Yue,1– 3,&ast; Deli Wang,1– 3 Ao Xiong,1– 3 Hui Zeng1– 3 1National & Local Joint Engineering Research Centre of Orthopaedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Shenzhen Key Laboratory of Orthopaedic Diseases and Biomaterials Research, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China; 3Department of Bone & Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ao Xiong; Hui Zeng, Email xiongao@189.cn; zenghui@pkuszh.comPurpose: Over the past 24 years, significant advancements have been made in applying artificial intelligence (AI) to musculoskeletal (MSK) diseases. However, there is a lack of analytical and descriptive investigations on the trajectory, essential research directions, current research scenario, pivotal focuses, and future perspectives. This research aims to provide a thorough update on the progress in AI for MSK diseases over the last 24 years.Methods: Data from the Web of Science database, covering January 1, 2000, to March 1, 2024, was analyzed. Using advanced analytical tools, we conducted comprehensive scientometric and visual analyses.Results: The findings highlight the predominant influence of the USA, which accounts for 28.53% of the total publications and plays a key role in shaping research in this field. Notable productivity was seen at institutions such as the University of California, San Francisco, Harvard Medical School, and Seoul National University. Valentina Pedoia is identified as the most prolific contributor. Scientific Reports had the highest number of publications in this area. The five most significant diseases are joint diseases, bone fractures, bone tumors, cartilage diseases, and spondylitis.Conclusion: This comprehensive scientometric assessment benefits both experienced researchers and newcomers, providing quick access to essential information and fostering the development of innovative concepts in this field. Keywords: artificial intelligence, musculoskeletal diseases, scientometrics, data visualization, global scientific frontiers

Di Wang,1,2 Qiqi Li,1,2 Chunsheng Xiao,2 Hao Wang,2 Shujun Dong1 1The First Outpatient Department, Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, 130021, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of ChinaCorrespondence: Hao Wang, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Chaoyang District, Changchun, 130022, People’s Republic of China, Tel +86-431-85262110, Email wangh@ciac.ac.cn Shujun Dong, The First Outpatient Department, Hospital of Stomatology, Jilin University, Room 101, Building G5, Phase 3, China Resources Ziyun Mansion, the Intersection of Jinhu Road and Nanhu Middle Street, Nanguan District, Changchun, 130021, People’s Republic of China, Tel +86-431-80621155, Email dsj@jlu.edu.cnAbstract: Periodontitis is a disease of inflammation that affects the tissues supporting the periodontium. It is triggered by an immunological reaction of the gums to plaque, which leads to the destruction of periodontal attachment structures. Periodontitis is one of the most commonly recognized dental disorders in the world and a major factor in the loss of adult teeth. Scaling and root planing remain crucial for managing patients with persistent periodontitis. Nevertheless, exclusive reliance on mechanical interventions like periodontal surgery, extractions, and root planning is insufficient to halt the progression of periodontitis. In response to the problem of bacterial resistance, some researchers are committed to finding alternative therapies to antibiotics. In addition, some scholars focus on finding new materials to provide a powerful microenvironment for periodontal tissue regeneration and promote osteogenic repair. Nanoparticles possess distinct therapeutic qualities, including exceptional antibacterial, anti-inflammatory, and antioxidant properties, immunomodulatory capacities, and the promotion of bone regeneration ability, which made them can be used for the treatment of periodontitis. However, there are many problems that limit the clinical translation of nanoparticles, such as toxic accumulation in cells, poor correlation between in vitro and in vivo, and poor animal-to-human transmissibility. In this paper, we review the present researches on nanoparticles in periodontitis treatment from the perspective of three main categories: inorganic nanoparticles, organic nanoparticles, and nanocomposites (including nanofibers, hydrogels, and membranes). The aim of this review is to provide a comprehensive and recent update on nanoparticles-based therapies for periodontitis. The conclusion section summarizes the opportunities and challenges in the design and clinical translation of nanoparticles for the treatment of periodontitis. Keywords: anti-inflammatory, antibacterial, guided tissue regeneration, nanofibers, hydrogel, films

Yuting Xiang,1,2,&ast; Li Tang,1,&ast; Hua Pang,3 Han Xu,1,2 Yiman He,1,2 Yuyue Feng,3 Linjun Ju,3 Liang Zhang,1 Dong Wang1 1Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Nuclear Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Zhang; Dong Wang, Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400042, People’s Republic of China, Email zhangliang338@cqmu.edu.cn; wang57554@163.comBackground: The inadequate perfusion, frequently resulting from abnormal vascular configuration, gives rise to tumor hypoxia. The presence of this condition hinders the effective delivery of therapeutic drugs and the infiltration of immune cells into the tumor, thereby compromising the efficacy of treatments against tumors. The objective of this study is to exploit the thermal effect of ultrasound (US) in order to induce localized temperature elevation within the tumor, thereby facilitating vasodilation, augmenting drug delivery, and enhancing immune cell infiltration.Methods: The selection of US parameters was based on intratumor temperature elevation and their impact on cell viability. Vasodilation and hypoxia improvement were investigated using enzyme-linked immunosorbent assay (ELISA) and immunofluorescence examination. The distribution and accumulation of commercial pegylated liposomal doxorubicin (PLD) and PD-L1 antibody (anti-PD-L1) in the tumor were analyzed through frozen section analysis, ELISA, and in vivo fluorescence imaging. The evaluation of tumor immune microenvironment was conducted using flow cytometry (FCM). The efficacy of US-enhanced chemotherapy in combination with immunotherapy was investigated by monitoring tumor growth and survival rate after various treatments.Results: The US irradiation condition of 0.8 W/cm2 for 10 min effectively elevated the tumor temperature to approximately 40 °C without causing any cellular or tissue damage, and sufficiently induced vasodilation, thereby enhancing the distribution and delivery of PLD and anti-PD-L1 in US-treated tumors. Moreover, it effectively mitigated tumor hypoxia while significantly increasing M1-phenotype tumor-associated macrophages (TAMs) and CD8+ T cells, as well as decreasing M2-phenotype TAMs. By incorporating US irradiation, the therapeutic efficacy of PLD and anti-PD-L1 was substantially boosted, leading to effective suppression of tumor growth and prolonged survival in mice.Conclusion: The application of US (0.8 W/cm2 for 10 min) can effectively induce vasodilation and enhance the delivery of PLD and anti-PD-L1 into tumors, thereby reshaping the immunosuppressive tumor microenvironment and optimizing therapeutic outcomes.Keywords: ultrasound, thermal effect, vasodilatation, drug delivery, tumor microenvironment

Yanxia Guo,&ast; Zhihua Yao,&ast; Yan Feng, Dan Wang, Yizheng Wang, Jingyan Lin Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingyan Lin, Email linjingyan@nsmc.edu.cnBackground: The novel short-acting benzodiazepine drug, remimazolam tosilate, has been employed for sedation during endoscopic procedures. The optimal loading dosage of remimazolam tosilate in gastroscopy for elderly patients when co-administered with fentanyl remains unclear. Therefore, the primary objective of our research was to ascertain the median effective dose (ED50) and the 95% effective dose (ED95) of remimazolam tosilate in combination with various fentanyl dosages for elderly patients undergoing painless gastroscopy.Methods: Seventy-five patients aged ≥ 65 years and American Society of Anesthesiologists (ASA) class I–III were recruited to undergo elective painless gastroscopy. All patients were randomized assigned to group F1, group F2, and group F3, and were injected intravenously with different doses of fentanyl (0.5 ug/kg, 1 ug/kg, and 1.5 ug/kg) 3 minutes prior to the administration of remimazolam tosilate, respectively. The initial preset dose of remimazolam tosilate was 0.3 mg/kg in group F1, 0.2 mg/kg in group F2, 0.15 mg/kg in group F3. The dose gradient was 0.02 mg/kg per group according to the up-and-down sequential method. Probibt regression model was employed to determine the ED50 and ED95 of remimazolam tosilate.Results: The ED50 of remimazolam tosilate in group F3 was lower than that in group F1 and F2 (0.095 [0.088– 0.108] mg/kg vs 0.162 [0.153– 0.171] mg/kg; 0.258 [0.249– 0.266] mg/kg, p < 0.05). The ED95 of remimazolam tosilate was 0.272 mg/kg (95% CI: 0.264– 0.295 mg/kg) in group F1, 0.175 mg/kg (95% CI: 0.167– 0.200 mg/kg) in group F2 and 0.109 mg/kg (95% CI: 0.101– 0.135 mg/kg) in group F3. The total dosage of remimazolam tosilate decreased gradually with the increasing of fentanyl (p < 0.001). The frequency of injection pain was higher in group F1 compared to groups F2 and F3 (p < 0.05). The patients in group F3 had a lower incidence of hypotension than in groups F1 and F2 (p < 0.05). There was no respiratory depression, intraoperative consciousness, dizziness or delirium in the three groups.Conclusion: The concurrent use of fentanyl reduces the dosage of remimazolam tosilate required for sedative gastroscopy in elderly patients in a dose-dependent manner. Moreover, 1.5 ug/kg fentanyl combined with remimazolam tosilate may reduce the incidence of hypotension and injection pain. These findings should be confirmed in a large-scale study.Keywords: painless gastroscopy, elderly patients, median effective dose, fentanyl, remimazolam tosilate

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

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

Liang Ruan,1,2 Shuailei Xu,1,2 Yuhan Qin,2 Huihong Tang,1,2 Xudong Li,1,2 Gaoliang Yan,2 Dong Wang,2 Chengchun Tang,2 Yong Qiao2 1School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Chengchun Tang; Yong Qiao, Department of Cardiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, People’s Republic of China, Email tangchengchun@hotmail.com; jinyong8866@163.comPurpose: Red blood cell distribution width to albumin ratio (RAR) is a novel inflammatory biomarker that independently predicts adverse cardiovascular events and acute kidney injury. This study aimed to assess the predictive value of RAR for cardio-renal syndrome type I (CRS-I) risk in acute myocardial infarction (AMI) patients.Patients and methods: This study retrospectively enrolled 551 patients who were definitively diagnosed as AMI between October 2021 and October 2022 at the Affiliated Zhongda Hospital of Southeast University. Participants were divided into two and four groups based on the occurrence of CRS-I and the quartiles of RAR, respectively. Demographic data, laboratory findings, coronary angiography data, and drug utilization were compared among the groups. Logistic regression and receiver operating characteristic curve (ROC) analysis were performed to identify independent risk factors for CRS-I and evaluated the predictive value of RAR for CRS-I.Results: Among the cohort of 551 patients, 103 (18.7%) developed CRS-I. Patients with CRS-I exhibited significantly elevated RAR levels compared to those without the condition, and the incidence of CRS-I correlated with escalating RAR. Univariate and multivariate logistic regression analyses identified RAR as an independent risk factor for CRS-I. ROC curves analysis demonstrated that RAR alone predicted CRS-I with an area under the curve (AUC) of 0.683 (95% CI=0.642– 0.741), which was superior to the traditional inflammatory marker C-reactive protein (CRP). Adding the variable RAR to the model for predicting the risk of CRS-I further improved the predictive value of the model from 0.808 (95% CI=0.781– 0.834) to 0.825 (95% CI=0.799– 0.850).Conclusion: RAR is an independent risk factor for CRS-I, and high levels of RAR are associated with an increased incidence of CRS-I in patients with AMI. RAR emerges as a valuable and readily accessible inflammatory biomarker that may play a pivotal role in risk stratification in clinical practice.Keywords: acute myocardial infarction, cardio-renal syndrome type I, red blood cell distribution width to albumin ratio, inflammatory

Donghao Wang,1,&ast; Yuting Zhang,1,&ast; Qiming Gan,1,&ast; Xiaofen Su,1,&ast; Haojie Zhang,1,2,&ast; Yanyan Zhou,1 Zhiyang Zhuang,1 Jingcun Wang,1 Yutong Ding,1 Dongxing Zhao,1 Nuofu Zhang1 1State Key Laboratory of Respiratory Disease, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, National Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2The Clinical Medicine Department, Henan University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nuofu Zhang; Dongxing Zhao, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, National Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Tel +86-13600460056 ; +86-13650901411, Email nfzhanggird@163.com; rieast@163.comObjective: Compared to low arousal threshold (AT), high AT is an easily overlooked characteristic for obstructive sleep apnea (OSA) severity estimation. This study aims to evaluate the relationship between high AT, hypertension and diabetes in OSA, compared to those with apnea–hypopnea index (AHI).Methods: A total of 3400 adults diagnosed with OSA were retrospectively recruited. Propensity score matching (PSM) was conducted to further categorize these patients into the low and high AT groups based on the strategy established by previous literature. The different degrees of AHI and quantified AT (AT score) were subsequently measured. The correlation of AT and AHI with the occurrence of various comorbidities in OSA was estimated by logistic regression analysis with odds ratio (OR).Results: After PSM, 938 pairs of patients arose. The median AT score of high and low AT group was 21.7 and 12.2 scores, and the adjusted OR of high AT for hypertension and diabetes was 1.31 (95% CI = 1.07– 1.62, P < 0.01) and 1.45 (95% CI = 1.01– 2.08, P < 0.05), respectively. Compared to low AT score group, the OR significantly increased in patients with very high AT score (30 ≤ AT score), especially for diabetes (OR = 1.79, 95% CI = 1.02– 3.13, P < 0.05). The significant association was not observed in AHI with increasing prevalent diabetes.Conclusion: Higher AT is significantly associated with increased prevalence of hypertension and diabetes in patients with OSA. Compared with AHI, AT score is a potentially comprehensive indicator for better evaluating the relationship between OSA and related comorbidities.Keywords: obstructive sleep apnea, arousal threshold, apnea–hypopnea index, hypertension, diabetes

Rongge Jiang,1 Haibai Liu,2 Xue Jiang,2 Ding Wang,2 Xiaoyu Li,2 Yi Shang3 1Neurosurgery Department 1, Baoding No.1 Central Hospital, Baoding, 071000, People’s Republic of China; 2Department of Nursing, Shijiazhuang Medical College, Shijiazhuang, 050599, People’s Republic of China; 3Department of Mammary, Shijiazhuang Fourth Hospital, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Xiaoyu Li, Shijiazhuang Medical College, No. 1 Tongxin Road, Lingshou County, Shijiazhuang, Hebei, 050599, People’s Republic of China, Tel + 8613603117321, Email lixiaoyu_li03@126.comObjective: This study explores the impact of a nursing intervention grounded in empowerment theory, focusing on behavioral change, on brain metastasis patients post-breast cancer surgery.Methods: Between June 2021 and June 2023, 102 patients diagnosed with brain metastasis after breast cancer surgery at Bao Ding No.1 Central Hospital were randomized into two groups. The control group (51 patients) received standard nursing care, while the observation group (51 patients) participated in a behavioral change nursing intervention influenced by empowerment theory. The evaluation metrics included measures of negative emotions, compliance with treatment protocols, overall quality of life, and nursing satisfaction, assessed at multiple time points during the study period.Results: The intervention led to significant reductions in negative emotions for all patients when compared to their pre-intervention statuses, with the observation group exhibiting notably lower depression and anxiety scores at one and three months post-intervention (P < 0.05). Additionally, this group achieved higher compliance scores and demonstrated greater improvements in quality of life than the control group (P < 0.05). Nursing satisfaction was also significantly higher in the observation group, with 96.08% reporting high satisfaction compared to 80.39% in the control group (P < 0.05).Conclusion: Implementing a nursing intervention that emphasizes behavioral changes and leverages empowerment theory significantly enhances the quality of life, reduces negative emotions, boosts compliance with treatment, and increases nursing satisfaction among patients with brain metastasis following breast cancer surgery. This suggests that such interventions could be a valuable component of postoperative care for this patient population.Keywords: behavioral change, empowerment theory, negative emotions, nursing intervention, brain metastasis, breast cancer, quality of life

Wenxue Liu,1 Yapeng Wang,2 Yi Jiang,2 Shan Lu,1 Jiawei Zhu,3 Yuhuan Tian,2 Jun Pan,1 Zhenjun Xu,1 Dongjin Wang1 1Institute of Cardiothoracic Vascular Disease, Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 2Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, People’s Republic of China; 3Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Dongjin Wang; Zhenjun Xu, Institute of Cardiothoracic Vascular Disease, Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China, Email wangdongjin@njglyy.com; xzj881225@163.comBackground: Postoperative delirium (POD) significantly impacts patient outcomes after acute type A aortic dissection (ATAAD) surgeries. This study investigates the role of Neuronal Pentraxin 2 (NPTX2) as a potential biomarker for POD in ATAAD patients.Methods: This secondary analysis involved ATAAD patients from a prospective observational study. Serum NPTX2 levels were measured preoperatively and immediately postoperatively using Enzyme-Linked Immunosorbent Assay (ELISA). Delirium was assessed using the Confusion Assessment Method (CAM) or CAM for the ICU (CAM-ICU). Statistical analyses included the Pearson Correlation Coefficient and multivariate logistic regression to evaluate the association between NPTX2 levels and POD.Results: Among the 62 patients included, 46.77% developed POD. Patients with POD had significantly lower preoperative and postoperative serum NPTX2 levels. The Receiver Operating Characteristic (ROC) curve analysis showed that postoperative NPTX2 had a strong predictive capability for POD (AUC = 0.895). The optimal cutoff for postoperative NPTX2 in predicting POD was less than 421.4 pg/mL. Preoperative NPTX2 also demonstrated predictive value, albeit weaker (AUC = 0.683).Conclusion: Serum NPTX2 levels, both preoperatively and postoperatively, are promising biomarkers for predicting POD in ATAAD patients. These findings suggest that NPTX2 could be instrumental in early POD detection and intervention strategies.Keywords: acute type a aortic dissection, postoperative delirium, NPTX2, biomarker

Zhenhu Zhang,1,&ast; Bin Shang,1,&ast; Xinyu Mao,1 Yamin Shi,2 Guodong Zhang,1 Dong Wang1 1Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China; 2School of Foreign Languages, Shandong University of Finance and Economics, Jinan, 250014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong Wang, Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jing Wu Road, Jinan, Shandong, 250021, People’s Republic of China, Tel +8615168863605, Email sdphwd@163.comBackground: Esophageal squamous cell carcinoma (ESCC) is an aggressive and fatal malignancy that leads to epithelial cancer. The association between epithelial cell heterogeneity, prognosis, and immune response in this cancer remains uncertain. This study aimed to investigate epithelial cell heterogeneity in ESCC and develop a predictive risk model using the identified cell types.Methods: Single-cell RNA sequencing (scRNA-seq) and differential ESCC gene data were accessed from the Gene Expression Omnibus. Functional enrichment analysis, inferCNV, cell development trajectories, and intercellular communication were analyzed following epithelial cell characterization. Differentially expressed ESCC (n = 773) and epithelial cell marker genes (n = 3407) were intersected to obtain core genes, and epithelial cell-related prognostic genes were identified. LASSO regression analysis was used to construct a prognostic model. The external dataset GSE53624 was used to further validate the stability of the model. Drug sensitivity predictions, and immune cell infiltration were analyzed. Molecular docking clarified the possible therapeutic role of β-sitosterol in ESCC. Finally, wound healing assay, cell colony, and transwell assay were constructed to detect the effects of the core gene PDLIM2 on ESCC cell proliferation, invasion, and migration.Results: Eight cell clusters were identified, and epithelial cells were categorized into tumor and paratumor groups. The tumor group possessed more chromosomal variants than the paratumor group. Epithelial cells were associated with multiple cell types and significantly correlated with the Wnt, transforming growth factor, and epidermal growth factor signaling pathways. From 231 intersected genes, five core genes were screened for use in the risk model: CTSL, LAPTM4B, MYO10, NCF2, and PDLIM2. These genes may contribute to the cancerous transformation of normal esophageal epithelial cells and thereby act as biomarkers and potential therapeutic targets in patients with ESCC. β-Sitosterol furthermore displayed excellent docking potential with these genes. Meanwhile, further experiments demonstrated that the gene PDLIM2 plays a major role in the progression of oesophageal squamous carcinoma.Conclusion: We successfully developed a risk model for the prognosis of ESCC based on epithelial cells that addresses the response of ESCC to immunotherapy and offers novel cancer treatment options.Keywords: ESCC, epithelial cells, risk signature, β-sitosterol, TME

Chao Hong,1,2,&ast; Anni Wang,1,&ast; Jiaxuan Xia,1 Jianming Liang,1,3 Ying Zhu,1 Dan Wang,1,4 Huaxing Zhan,4 Chunbo Feng,5 Xinnan Jiang,5 Junjie Pan,6 Jianxin Wang1,7 1Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, 201203, People’s Republic of China; 2School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 4Xiamen Ginposome Pharmaceutical Co., Ltd, Xiamen, 361026, People’s Republic of China; 5R&D Center, Shanghai Jahwa United Co., Ltd, Shanghai, 200082, People’s Republic of China; 6Department of Cardiology, Huashan Hospital, Fudan University, Shanghai, 200040, People’s Republic of China; 7Institute of Integrated Chinese and Western Medicine, Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junjie Pan; Jianxin Wang, Email junjie112@163.com; jxwang@shmu.edu.cnBackground: Most solid tumors are not diagnosed and treated until the advanced stage, in which tumors have shaped mature self-protective power, leading to off-target drugs and nanomedicines. In the present studies, we established a more realistic large tumor model to test the antitumor activity of a multifunctional ginsenoside Rh2-based liposome system (Rh2-lipo) on advanced breast cancer.Methods: Both cholesterol and PEG were substituted by Rh2 to prepare the Rh2-lipo using ethanol-water system and characterized. The effects of Rh2-lipo on cell uptake, penetration of the tumor spheroid, cytotoxicity assay was investigated with 4T1 breast cancer cells and L929 fibroblast cells. The 4T1 orthotopic-bearing large tumor model was established to study the targeting effect of Rh2-lipo and inhibitory effect of paclitaxel loaded Rh2-lipo (PTX-Rh2-lipo) on advanced breast tumors.Results: Rh2-lipo exhibit many advantages that address the limitations of current liposome formulations against large tumors, such as enhanced uptake in TAFs and tumor cells, high targeting and penetration capacity, cytotoxicity against TAFs, normalization of the vessel network, and depletion of stromal collagen. In in vivo study, PTX-Rh2-lipo effectively inhibiting the growth of advanced breast tumors and outperformed most reported PTX formulations, including Lipusu® and Abraxane®.Conclusion: Rh2-lipo have improved drug delivery efficiency and antitumor efficacy in advanced breast cancer, which offers a novel promising platform for advanced tumor therapy. Keywords: nanomedicine, tumor microenvironment, chemotherapy, tumor-associated fibroblast

Ziwen Wang,1,2 Jiaxuan Fang,1,2 Shigao Zu,1,2 Qianru Sun,1,2 Zixin Song,1,2 Jiman Geng,1,2 Dongdong Wang,1,2 Meng Li,1,2 Changtao Wang1,2 1Beijing Key Laboratory of Plant Resource Research and Development, Beijing Technology and Business University, Beijing, 100048, People’s Republic of China; 2School of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing, 100048, People’s Republic of ChinaCorrespondence: Dongdong Wang; Changtao Wang, Beijing Technology and Business University, Beijing, 100048, People’s Republic of China, Tel/Fax +86 158 1135 7756, Email wdd@btbu.edu.cn; wangct@th.btbu.edu.cnPurpose: To produce Panax notoginseng extract as a cosmetic ingredient through Saccharomyces cerevisiae fermentation.Methods: We first compared the total sugar content, polysaccharide content, reducing sugar content, total phenolic content, total saponin content, DPPH free radical, ABTS free radical, hydroxyl free radical scavenging ability and ferric reducing antioxidant power (FRAP) of Panax notoginseng fermented extract (pnFE) and unfermented extract (pnWE). Their potential correlations were analyzed by Pearson’s correlation analysis. Then, the oxidative stress model of H2O2-induced MSFs was used to evaluate the effects of different pnFE on MSF viability, reactive oxygen species (ROS), malondialdehyde (MDA), and the activities of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) to explore their protective effects on MSFs subjected to H2O2-induced cellular oxidative damage. Finally, their safety and stability were evaluated by using the red blood cell (RBC) test and hen’s egg test-chorioallantoic membrane (HET-CAM) assay, and changes in pH and content of soluble solids, respectively.Results: Compared with pnWE, pnFE has more active substances and stronger antioxidant capacity. In addition, pnFE has a protective effect on H2O2-induced oxidative stress in MSFs with appropriate safety and stability.Conclusion: PnFE has broad application prospects in the field of cosmetics.Keywords: Panax notoginseng, Saccharomyces cerevisiae, fermentation, oxidative stress, fibroblast cells, cosmetic ingredients

Mi Zhou,1 Jieyun Li,1 Xinang Xiao,1 Jiekee Lim,1 Zhikui Tian,2 Dongjun Wang,3 Naijin Zhang,4 Zhaoxia Xu1,5 1College of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2College of Rehabilitation Medicine, Qilu Medical University, Zibo, 255000, People’s Republic of China; 3College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan, 063210, People’s Republic of China; 4College of Public Health and Health Sciences, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of China; 5Shanghai Key Laboratory of Health Identification and Assessment, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Zhaoxia Xu, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New Area, Shanghai, 201203, People’s Republic of China, Email zhaoxia7001@shutcm.edu.cnAim of the Study: This study analyzes research on TCM formulae in CHD over the past 30 years, using VOSviewer and CiteSpace. It aims to highlight key trends and hotspots in the field.Materials and Methods: The core database of Web of Science was collected, and the search time range was from the establishment of the database to the present (August 2023) for the literature related to the study of TCM prescriptions in CHD, and the information on the number of literature, countries, journals, authors, institutions, keywords were summarized by applying the software VOSviewer and CiteSpace.Results: A total of 135 kinds of literature were included. The number of published journal papers on research on TCM therapeutic formulae for CHD showed an upward trend; China was the most prolific country in this field; the largest number of papers were published in Evid Based Complement Alternat Med, MEDICINE; the average number of citations for authors and institutional analysis revealed that Xu Hao of China Academy of Traditional Chinese Medicine, Mao Jingyuan of Tianjin University of Traditional Chinese Medicine, and Shang Hongcai of Beijing University of Traditional Chinese Medicine constituted the core team of researchers studying the study of TCM formulae for CHD; the keyword analysis suggests that there are mainly 42 specifically named TCM formulae for the treatment of CHD, which are classified into a total of 7 major categories, and the research direction is mainly in the clinical efficacy study of different TCM therapeutic formulae and other aspects.Conclusion: This study shows that there are more types of TCM therapeutic formulae for CHD, and the related research has a good prospect. It is foreseeable that more relevant research results will rely on the study of network pharmacology, signalling pathways, and action targets of TCM therapeutic formulae. Keywords: coronary heart disease, Traditional Chinese Medicine, therapeutic formulae, scientometrics

Lili Wang,1,2,&ast; Lu Nie,3,&ast; Yue Liu,4,&ast; Liang Hu,2 Aiping Zhou,2 Dongjiang Wang,2 Xuebin Xu,4 Jian Guo2 1Department of Laboratory Medicine, Zhoushan Women and Children Hospital, Zhoushan, People’s Republic of China; 2Department of Laboratory Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, People’s Republic of China; 3Department of Laboratory Medicine, The First People’s Hospital of Foshan, Foshan, Guangdong, People’s Republic of China; 4Shanghai Municipal Center for Disease Control and Prevention, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Guo; Xuebin Xu, Email guojian1110@126.com; xxb72@sina.comBackground: This study aimed to provide epidemiological features of Salmonella enterica serovar Rissen, determine antimicrobial susceptibility, virulence gene profiles, and describe the potential association of S. Rissen from different sources in China.Methods: During 2008– 2019, a total of non-repetitive 228 S. Rissen isolates were collected from human, animals and environment in China. The antimicrobial susceptibility test, screening of antimicrobial and virulence genes by PCR, and pulsed-field gel electrophoresis (PFGE) were performed.Results: Among the 154 isolates from human, the majority of the cases (80.5%) occurred in summer, and S. Rissen was mainly detected in people aged 21– 40 (37.7%) and 41– 60 (28.6%) years old, and 74 non-human source S. Rissen strains were identified, with pork being the most common source. About 93.4% isolates were resistant to at least one of the 12 tested antimicrobial agents, and high frequencies of resistance were observed for tetracyclines (91.2%), trimethoprim-sulfamethoxazole (74.1%) and ampicillin (67.5%). A total of 171 (75%) isolates were resistant to at least three categories of antimicrobials, and the most common resistance profile was Tetracycline(s)-β-Lactams-Sulfonamides. The resistance rates to chloramphenicol, quinolones and sulfafurazole were significantly higher in strains isolated from human compared to non-human source strains. Among these isolates, the β-Lactams resistance was mainly associated with gene blaTEM (54.7%), sulfonamide resistance with sul2 (45.7%) and sul3 (54.3%), tetracycline resistance with tetA (81.3%). All the isolates harbored virulence genes hilA, sopB, sciN, stn and ssrB, and most of them harbored ssaQ (98.7%), mgtC (98.7%) and invA (98.2%). The majority (91.7%) of S. Rissen isolates showed high similarity (> 80%) with each other in PFGE patterns and came from human, animals and environment.Conclusion: The high frequencies of multidrug resistance and probable clonal dissemination in this serovar call for the necessity of systematic surveillance on S. Rissen in China.Keywords: Salmonella Rissen, antimicrobial susceptibility test, resistance genes, virulence genes, pulsed-field gel electrophoresis

Dongfang Wang,1,2 Andrew Scherffius,3 Xuan Ouyang,1 Qijian Deng1 1Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2School of Psychology, Centre for Studies of Psychological Applications, Guangdong Key Laboratory of Mental Health and Cognitive Science, Ministry of Education Key Laboratory of Brain Cognition and Educational Science, South China Normal University, Guangzhou, People’s Republic of China; 3Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USACorrespondence: Qijian Deng, Mental Health Institute, The Second Xiangya Hospital of Central South University, Changsha, 410011, People’s Republic of China, Email dengqijian@csu.edu.cnBackground: Depressive symptoms are common among HIV-positive men who have sex with men (MSM). This study aims to explore (1) the relationship between family functioning and depressive symptoms and (2) the mediating roles of stigma and resilience in the relationship among HIV-positive MSM.Methods: We used data from a cross-sectional study of a convenience sample in Hunan Province, China, conducted in 2019. The data analysis included 191 HIV-positive MSM with an average age of 26.98 years. All participants completed self-report questionnaires on demographic variables, family functioning, stigma, resilience, and depressive symptoms.Results: Better family functioning was significantly associated with lower depressive symptoms. Both stigma (Indirect effect = − 0.04, 95% CI, − 0.10 ~ − 0.001) and resilience (Indirect effect = − 0.06, 95% CI, − 0.12 ~ − 0.01) were significant partial mediators in the relationship between family functioning and depressive symptoms. A parallel and chain mediating role of stigma and resilience in the relationship between family functioning and depressive symptoms was also supported (Indirect effect = − 0.03, 95% CI, − 0.08 ~ − 0.01).Conclusion: Improving family functioning is crucial for alleviating depressive symptoms among HIV-positive MSM in China. Depression assessment and reduction should be an integral part of prevention and treatment programs targeting stigma and resilience.Keywords: HIV, men who have sex with men, family functioning, stigma, resilience, depressive symptoms

Bingna Xu,1 Chunping Chen,1 Dongfang Wang2,3 1Institute of Education, Xiamen University, Xiamen, People’s Republic of China; 2School of Psychology, South China Normal University, Guangzhou, People’s Republic of China; 3Centre for Studies of Psychological Applications, Guangdong Key Laboratory of Mental Health and Cognitive Science, Ministry of Education Key Laboratory of Brain Cognition and Educational Science, South China Normal University, Guangzhou, People’s Republic of ChinaCorrespondence: Chunping Chen, Institute of Education, Xiamen University, Siming Road, Xiamen, 361005, People’s Republic of China, Email 894906014@qq.com Dongfang Wang, School of Psychology, South China Normal University, Shipai Road, Guangzhou, 510631, People’s Republic of China, Email wdfpsyc@126.com; wangdf@m.scnu.edu.cnBackground: Current psychotic-like experiences (PLEs) are prevalent among adolescents. However, epidemiological data on the prevalence rate of current PLEs among college students and its clinical correlates are scarce and limited. To address this study gap, this study aimed to investigate the prevalence and correlates of current PLEs among Chinese college students.Methods: A cross-sectional study was designed with a sample of 18,578 college students in China. Each participant completed a survey on social-demographic characteristics variables, PLEs, sleep disturbance, depression, anxiety, and suicidal ideation. Logistic regression analyses were conducted to explore the influential factors for PLEs among all participants and suicidal ideation among those with PLEs.Results: Among Chinese college students, 40.3% of the participants reported having at least one PLE in the past month, while 7.5% had frequent PLEs. Males, age, residence location in town, left-behind experiences, poor family economic status, chronic physical illness, family history of mental disorder, BMI ≥ 28 [obesity], sleep disturbance, depression, anxiety, and suicidal ideation were independent correlates for frequent PLEs. Furthermore, the prevalence of suicidal ideation among participants with frequent PLEs was 32.1%. Lower grades, sleep disturbance, depression, and anxiety were independent predictors of suicidal ideation among college students who experience PLEs frequently.Conclusion: Current PLEs are widespread among Chinese college students. Suicidal ideation is largely prevalent among individuals who suffer frequent PLEs, suggesting that special measures and attention should be provided to these students based on relevant factors to prevent their suicidal ideation and behavior.Keywords: psychotic-like experiences, suicidal ideation, correlates, college students

Dawei Wang,&ast; Mengmeng Zhou,&ast; Yixin Hu School of Psychology, Shandong Normal University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yixin Hu, School of Psychology, Shandong Normal University, No. 88, East Wenhua Road, Jinan, Shandong Province, People’s Republic of China, Email huyixin2005@163.comPurpose: With the increasing prevalence of smart phones, adolescent smartphone addiction has garnered significant attention from researchers. Previous studies have revealed that smartphone addiction is associated with various internalization and externalization problems. Therefore, this present study aims to investigate the risk factors contributing to adolescent smartphone addiction.Methods: Study 1 recruited a sample of 540, 690, and 470 Chinese students aged between 10– 17 years for exploratory factor analysis, confirmatory factor analysis, and predictive validity analysis of the social pain scale. Study 2 utilized data from a sample of 718 Chinese students aged between 10– 17 years to examine the measurement model used revised social pain scale, smartphone addiction scale, harsh parenting scale, and depression sub-scale.Results: The present study revealed that (1)The Social Pain Scale had good applicability in Chinese adolescents; (2) There were significant, positive correlations among harsh parenting, smartphone addiction, depression and social pain; (3) Social pain and depression played a partially serial mediating role in the relationship between harsh parenting and smartphone addiction, and similarly the relationship between paternal harsh parenting and smartphone addiction, while a completely serial mediating role in the relationship between maternal harsh parenting and smartphone addiction.Conclusion: This study provides a direct path (improving parenting style) and an indirect path (reducing social pain to reduce depression) regarding interventions for adolescents with smartphone addiction, and establishes a basis for improving the situation of adolescent smartphone addiction.Keywords: harsh parenting, smartphone addiction, adolescents, multiple mediation model

Yixue Hu,1 Dongna Wang,2 Tianyu Zhang,2 Meng Lei,3 Yingnan Luo,2 Zhimeng Chen,3 Yuting Li,2 Dandan Duan,2 Liefeng Zhang,1 Yongqiang Zhu1,2 1College of Life Science, Nanjing Normal University, Nanjing, People’s Republic of China; 2School of Food and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, People’s Republic of China; 3College of Science, Nanjing Forestry University, Nanjing, People’s Republic of ChinaCorrespondence: Liefeng Zhang; Yongqiang Zhu, College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Qixia District, Nanjing, 210023, People’s Republic of China, Tel/Fax +86-25-85898184; +86-25-85891591, Email lfzhang@njnu.edu.cn; zhyqscu@hotmail.comIntroduction: Tumor hypoxia and invasion present significant challenges for the efficacy of photodynamic therapy (PDT) in triple-negative breast cancer (TNBC). This study developed a mitochondrial targeting strategy that combined PDT and gene therapy to promote each other and address the challenges.Methods: The positively charged amphiphilic material triphenylphosphine-tocopherol polyethylene glycol succinate (TPP-TPGS, TPS) and the photosensitizer chloride e6 (Ce6) formed TPS@Ce6 nanoparticles (NPs) by hydrophobic interaction. They electrostatically condensed microRNA-34a (miR-34a) to form stable TPS@Ce6/miRNA NPs.Results: Firstly, Ce6 disrupted the lysosomal membrane, followed by successful delivery of miR-34a by TPS@Ce6/miRNA NPs. Meanwhile, miR-34a reduced ROS depletion and further enhanced the effectiveness of PDT. Consequently, the mutual promotion between PDT and gene therapy led to enhanced anti-tumor effects. Furthermore, the TPS@Ce6/miRNA NPs promoted apoptosis by down-regulating Caspase-3 and inhibited tumor cell migration and invasion by down-regulating N-Cadherin. In addition, in vitro and in vivo experiments demonstrated that the TPS@Ce6/miRNA NPs achieved excellent anti-tumor effects. These findings highlighted the enhanced anticancer effects and reduced migration of tumor cells through the synergistic effects of PDT and gene therapy.Conclusion: Taken together, the targeted co-delivery of Ce6 and miR-34a will facilitate the application of photodynamic and genic nanomedicine in the treatment of aggressive tumors, particularly TNBC. Keywords: photodynamic therapy, gene therapy, hypoxia, invasion, mitochondrial target, triple-negative breast cancer

Donghao Wang,1,&ast; Yating Chen,1,&ast; Yutong Ding,1,&ast; Yongkang Tang,1,&ast; Xiaofen Su,1,&ast; Shiwei Li,1 Haojie Zhang,1,2 Yanyan Zhou,1 Zhiyang Zhuang,1 Qiming Gan,1 Jingcun Wang,1 Yuting Zhang,1 Dongxing Zhao,1 Nuofu Zhang1 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510160, People’s Republic of China; 2The Clinical Medicine Department, Henan University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nuofu Zhang, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510160, People’s Republic of China, Tel +86-13600460056, Email nfzhanggird@163.comBackground: Obstructive sleep apnea (OSA) is a common chronic disease with various comorbidities. The cardiometabolic index (CMI) reflects visceral fat tissue distribution and function, assessing the risk of obesity-related conditions such as metabolic syndrome (MetS) and stroke, which are strongly connected to OSA. The relationship between CMI with OSA and OSA combined with MetS (OMS) remains unclear. This study aims to evaluate the screening value of CMI for OSA and OMS, compared to the lipid accumulation product (LAP).Methods: A total of 280 participants who underwent polysomnography were finally included, with the measurements of metabolic-related laboratory test results such as total cholesterol and triglyceride. Receiver operating curve (ROC) analysis and calculation of the area under the curve (AUC) were conducted to assess the screening potential of CMI, LAP, and the logistic regression models established based on them for OSA and OMS. The Youden index, sensitivity, and specificity were used to determine the optimal cutoff points.Results: ROC curve analysis revealed that the AUCs for CMI in screening OSA and OMS were 0.808 and 0.797, and the optimal cutoff values were 0.71 (sensitivity 0.797, specificity 0.776) and 0.89 (sensitivity 0.830, specificity 0.662), respectively, showing higher Youden index than LAP. The AUCs of screening models based on CMI for OSA and OMS were 0.887 and 0.824, respectively.Conclusion: CMI and LAP can effectively screen for OSA and OMS, while CMI has more practical cutoff values for identifying the diseased states. Screening models based on CMI demonstrate a high discriminatory ability for OSA and OMS, which needs verification in a large-scale population.Keywords: obstructive sleep apnea, metabolic syndrome, cardiometabolic index, lipid accumulation products, screening model

Long Lv,1,&ast; Jinghu Du,1,&ast; Daorong Wang,2 Zeqiang Yan2 1Department of General Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, People’s Republic of China; 2Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Daorong Wang; Zeqiang Yan, Department of Gastroenterology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, 441021, People’s Republic of China, Tel +13581425716 ; +13597505970, Email 415004128@qq.com; yzqi48959@163.comBackground: Gastric cancer (GC) is a common fatal malignancy. The aim of this study was to explore and validate the tumor-suppressive role and mechanism of Radix Bupleuri in GC.Methods: The active constituents of Radix Bupleuri were screened using TCMSP database. SwissTargetPrediction database was used to predict potential target genes of the compounds. GeneCards, TTD, DisGeNET, OMIM, and PharmGKB databases were used to search for GC-related targets. STRING database and Cytoscape 3.10 software were used for protein–protein interaction network construction and screening of core targets. DAVID database was used for GO and KEGG analyses. Core targets were validated using molecular docking. Cell proliferation and apoptosis were detected using CCK-8 and flow cytometry after GC cells were treated with isorhamnetin. The mRNA and protein expression levels of genes were detected using qRT PCR and Western blot. The metastasis potential of GC cells was evaluated in a nude mouse model.Results: A total of 371 potential targets were retrieved by searching the intersection of Radix Bupleuri and GC targets. Petunidin, 3’,4’,5’,3,5,6,7-Heptamethoxyflavone, quercetin, kaempferol, and isorhamnetin were identified as the main bioactive compounds in Radix Bupleuri. SRC, HSP90AA1, AKT1, and EGFR, were core targets through which Radix Bupleuri suppressed GC. The tumor-suppressive effect of Radix Bupleuri on GC was mediated by multiple pathways, including PI3K-AKT, cAMP, and TNF signaling. The key compounds of Radix Bupleuri had good binding affinity with the core target. Isorhamnetin, a key component of Radix Bupleuri, could inhibit proliferation and metastasis, and induces apoptosis of GC cells. In addition, isorhamnetin could also reduce the mRNA expression of core targets, and the activation of PI3K/AKT pathway.Conclusion: This study identified potential targets and pathways of Radix Bupleuri against GC through network pharmacology and molecular docking, providing new insights into the pharmacological mechanisms of Radix Bupleuri in GC treatment. Keywords: gastric cancer, Radix Bupleuri, network pharmacology, molecular docking

Xingtao Long,1 Qingming Jiang,2 Rengui Li,1 Dong Wang,1 Dongling Zou1 1Department of Gynaecological Oncology, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China; 2Department of Pathology, Chongqing University Cancer Hospital, Chongqing, People’s Republic of ChinaCorrespondence: Dongling Zou, Department of Gynaecological Oncology, Chongqing University Cancer Hospital, 181 Hanyu Road, Shapingba District, Chongqing, 400000, People’s Republic of China, Tel +8613657690699, Fax +8602365075612, Email cqzl_zdl@163.comIntroduction: Alveolar soft part sarcoma (ASPS) is a rare and distinct subtype of soft tissue sarcoma. This study aims to describe the unique presentation of ASPS in the female genital tract.Methods: Prognostic factors for cancer-specific overall survival (CSS) were evaluated using multivariate analyses.Results: In our case series, we identified a novel TFE3-PRCC gene fusion in a 24-year-old unmarried patient with cervical ASPS who underwent fertility-sparing surgery and remained recurrence-free for 41 months. The other two patients underwent radical hysterectomy and bilateral salpingo-oophorectomy. At the time of writing, the two patients had been disease-free for 49 and 71 months, fluorescence in situ hybridization showed break-apart signals for the ASPL-TFE3 gene. Among the 55 cases with available information from the PubMed/Medline database, most presented with localized disease, and at the last follow-up, all patients were alive and 45 patients showed no evidence of disease. The 5-year CSS rate in the female genital tract cohort from SEER database was 86.2%. Multivariate analysis revealed that older age was associated with a 1.042-fold increased risk of cancer-specific mortality (HR=1.042, 95% CI 1.022– 1.063, P < 0.001), involvement of soft tissue including the heart was associated with a 4.786-fold higher risk (HR=4.7868, 95% CI 1.681– 13.623, P= 0.003), and regional infiltration and distant metastasis were associated with approximately 8.6-fold and 18-fold higher risk of cancer-specific mortality compared to local disease, respectively (HR=8.652, 95% CI 2.529– 29.63, P = 0.001; HR=18.366, 95% CI 6.153– 54.817, P< 0.001). Patients who underwent radical excision did not show reduced cancer-specific mortality compared to those who underwent local excision (HR=0.492, 95% CI 0.224– 1.081, P = 0.078).Discussion: Previously unrecognized genetic diversity exists in ASPS. Patients with ASPS in the female genital tract have the lowest likelihood of presenting with a distant disease and are associated with a more favorable survival outcome.Keywords: ASPSCR1, TFE3, alveolar soft part sarcoma, fusion

Zhao Guo,1,&ast; Haoyun Song,1,&ast; Yingxia Tian,2,&ast; Jie Xu,3 Guokun Zhang,1 Yanan Guo,1 Rong Shen,1 Degui Wang1 1Department of Anatomy and Histology, Lanzhou University School of Basic Medical Sciences, Lanzhou, 730000, People’s Republic of China; 2Department of Internal Medicine, Gansu Provincial Academic Institute for Medical Research, Lanzhou, 730050, People’s Republic of China; 3Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Degui Wang; Rong Shen, Department of Anatomy and Histology, Lanzhou University School of Basic Medical Sciences, Lanzhou, 730000, People’s Republic of China, Tel +86 13893609120 ; +86 13909483373, Fax +86 931 8915023, Email wangdegui@lzu.edu.cn; shenr@lzu.edu.cnBackground: The evident side effects and decreased drug sensitivity significantly restrict the use of chemotherapy. However, nanoparticles based on biomaterials are anticipated to address this challenge.Methods: Through bioinformatics analysis and colon cancer samples, we initially investigated the expression level of RNF8 in colon cancer. Next, we constructed nanocarrier for delivering siRNF8 based on DNA tetrahedron (si-Tet), and Doxorubicin (DOX) was further intercalated into the DNA structure (si-DOX-Tet) for combination therapy. Further, the effects and mechanism of RNF8 inhibition on the sensitivity of colon cancer cells to DOX chemotherapy have also been studied.Results: RNF8 expression was increased in colon cancer. Agarose gel electrophoresis, transmission electron microscopy, and size distribution and potential analysis confirmed the successful preparation of the two nanoparticles, with particle sizes of 10.29 and 37.29 nm, respectively. Fluorescence imaging reveals that the carriers can be internalized into colon cancer cells and escape from lysosomes after 12 hours of treatment, effectively delivering siRNF8 and DOX. Importantly, Western blot analysis verified treatment with 50nM si-Tet silenced RNF8 expression by approximately 50% in colon cancer cells, and combined treatment significantly inhibited cell proliferation. Furthermore, the CCK-8 assay demonstrated that si-Tet treatment enhanced the sensitivity of colon cancer cells to the three chemotherapeutic drugs. Significant more DNA damage was detected after treatment with both si-Tet or si-DOX-Tet. Further flow cytometry analysis revealed that si-DOX-Tet treatment led to significantly more apoptosis, approximately 1.6-fold higher than treatment with DOX alone. Mechanistically, inhibiting RNF8 led to decreased ABCG2 expression and DOX efflux, but increased DNA damage, thereby enhancing the chemotherapeutic effect of DOX.Conclusion: We have successfully constructed si-DOX-Tet. By inhibiting the expression of RNF8, it enhances the chemotherapy sensitivity of DOX. Therefore, this tetrahedral FNA nanocarrier offers a new approach for the combined treatment of colon cancer. Keywords: DNA framework nucleic acid, RNF8, chemosensitivity, RNAi, colorectal cancer

Jiajia Dong,1 Mengyu Liu,1 Yawei Bian,1,2 Wei Zhang,1 Chen Yuan,1 Dongyun Wang,1 Zihui Zhou,1 Yue Li,1 Yonghong Shi1,2 1Department of Pathology, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Hebei Key Laboratory of Kidney Disease, Shijiazhuang, People’s Republic of ChinaCorrespondence: Yonghong Shi, Department of Pathology, Hebei Medical University, No. 361 East Zhongshan Road, Shijiazhuang, Hebei, 050017, People’s Republic of China, Tel +86 311 86266647, Email yonghongshi@163.comBackground: Diabetic kidney disease (DKD) is characterized by renal fibrosis, and the pathogenesis of renal fibrosis is still not definitely confirmed. MiR-204-5p plays an important role in the regulation of fibrosis, autophagy and oxidative stress. In this study, we aimed to investigate the role of miR-204-5p on renal damage in diabetic kidneys and the underlying mechanisms involved.Methods: In vivo, AAV-Ksp-miR-204-5p mimics were injected into mice via tail vein. In vitro, high glucose-induced HK-2 cells were treated with miR-204-5p inhibitor, miR-204-5p mimics, ATG5 siRNA, tertiary butyl hydroquinone (TBHQ), ML385, or 3-Methyladenine (3-MA). FISH and qRT-PCR were used to detect miR-204-5p expression. The expressions of protein and mRNA were detected by Western blotting, immunofluorescence, immunohistochemistry and qRT-PCR. The concentration of fibronectin in HK-2 cells culture medium was detected by ELISA.Results: The expression of miR-204-5p in diabetic kidneys was significantly inhibited than that in control group. Delivering miR-204-5p mimics increased miR-204-5p expression, improved renal function, inhibited renal fibrosis and oxidative stress, and restored autophagy in db/db mice. In vitro, the expression of miR-204-5p was inhibited by HG treatment in HK-2 cells. MiR-204-5p mimics effectively increased miR-204-5p expression and reduced fibronectin and collagen I expression, restored autophagy dysfunction, and increased Nrf2 expression, whereas these alterations were abrogated by Nrf2 inhibitor ML385, autophagy inhibitor 3-methyladenine (3-MA, 5 mM) treatment or ATG5 siRNA transfection in HG-induced HK-2 cells. In addition, miR-204-5p inhibitor significantly inhibited miR-204-5p expression and aggravated HG-induced fibronectin and collagen I expression, autophagy dysfunction, and decreased Nrf2 expression, while these alterations were abolished by Nrf2 activator TBHQ. Furthermore, the binding of miR-204-5p with Keap1 was confirmed by luciferase reporter assay and miR-204-5p negatively regulated Keap1 expression, resulting in the activation of Nrf2 pathway.Conclusion: MicroRNA-204-5p protects against the progression of diabetic renal fibrosis by restoring autophagy via regulating Keap1/Nrf2 pathway. Keywords: diabetic kidney disease, fibrosis, miR-204-5p, Keap1, Nrf2, autophagy

Jia Zhang,1,&ast; Danni Wang,1,&ast; Mingjing Chen,1 Jiajun Li,2 Wenxiang Huang1 1Department of Geriatrics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Infectious Diseases, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenxiang Huang, Department of Geriatrics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China, Tel +86 13883533808, Email wenxiang_huang@163.comAbstract: Acute genital ulcers (AGU) have been associated with various pathogens, such as Epstein–Barr virus (EBV) and cytomegalovirus (CMV). However, cases of AGU associated with coronavirus disease 2019 (COVID-19) are rare, and this disease significantly impairs human quality of life. In this case, we report a 37-year-old woman who presented with a five-day history of a painful genital ulcer and fever. A month earlier, she had experienced a COVID-19 infection that resolved without medical therapy. Physical examination revealed that multiple asymmetric ulcers presented on labia minora covered with whitish exudates. The patient, without any high-risk sexual behavior, or a personal or family history of autoimmune disorders or inflammatory bowel disease, was diagnosed with COVID-19-related AGU after ruling out other infectious and immune diseases. Following a two-week treatment of oral prednisone, her vulvar edema, ulcers, and fever improved significantly. This case suggests that AGU may be triggered by a COVID-19 infection.Keywords: COVID-19, SARS-CoV-2, acute genital ulcers, fever

Dingyue Wang, Gaosen Zhang, Yana Yu, Zhen Zhang Department of Ultrasound, the First Affiliated Hospital China Medical University, Shenyang City, Liaoning Province, 110001, People’s Republic of ChinaCorrespondence: Zhen Zhang, Email zhangzhen@cmu.edu.cnAbstract: Sarcopenia is an age-related condition characterized by the loss of skeletal muscle mass, muscular strength, and muscle function. In older adults, type 2 diabetes mellitus (T2DM) constitutes a significant health burden. Skeletal muscle damage and deterioration have emerged as novel chronic complications in patients with diabetes, often linked to their increased longevity. Diabetic sarcopenia has been associated with increased rates of hospitalization, cardiovascular events, and mortality. Nevertheless, effectively managing metabolic disorders in patients with T2DM through appropriate therapeutic interventions could potentially mitigate the risk of sarcopenia. Utilizing imaging technologies holds substantial clinical significance in the early detection of skeletal muscle mass alterations associated with sarcopenia. Such detection is pivotal for arresting disease progression and preserving patients’ quality of life. These imaging modalities offer reproducible and consistent patterns over time, as they all provide varying degrees of quantitative data. This review primarily delves into the application of dual-energy X-ray absorptiometry, computed tomography, magnetic resonance imaging, and ultrasound for both qualitative and quantitative assessments of muscle mass in patients with T2DM. It also juxtaposes the merits and limitations of these four techniques. By understanding the nuances of each method, clinicians can discern how best to apply them in diverse clinical scenarios.Keywords: diagnostic imaging, older adults, sarcopenia, skeletal muscle mass, type 2 diabetes mellitus

Min Dong,1,&ast; Xiumin Ma,2,&ast; Donglian Wang,3,&ast; Xiaobo Ma,4 Jin Zhang,5 Lianhua Yu,5 Qing Yang,6 Dakang Hu,5,7 Dengyan Qiao8 1Department of Pulmonary Diseases (Department of Respiratory and Critical Care Medicine), Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, Gansu, People’s Republic of China; 2State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3Department of Laboratory Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, People’s Republic of China; 4Department of Clinical Laboratory, the First Affiliated Hospital of Xiamen University (Xiamen Key Laboratory of Genetic Testing), Xiamen, People’s Republic of China; 5Department of Laboratory Medicine, Taizhou Municipal Hospital, Taizhou, Zhejiang, People’s Republic of China; 6Department of Laboratory Medicine, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 7Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 8Department of Laboratory Medicine, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou, Gansu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dakang Hu; Dengyan Qiao, Email 18111220048@fudan.edu.cn; 2985998299@qq.comObjective: To explore why serotype K2 accounts for a stable share in Klebsiella pneumoniae from pyogenic liver abscess (PLA).Methods: Totally 15 K2 K. pneumoniae strains from PLA, 21 K2 from non-PLA, and 31 K1 from PLA were collected from China. Sequence typing, molecular serotyping, regular PCR, and Galleria mellonella lethality were performed. A total of 12 virulence genes were detected: peg-344, allS, p-rmpA, p-rmpA2, c-rmpA, fimH, mrkD, iucA, iroN, irp2, entB, and wzi. The differences between K2 K. pneumoniae strains from PLA and non-PLA were investigated along with K1 ones.Results: Significant differences were found between K2 strains from PLA and non-PLA for the rates of virulence genes peg-344 and iucA. The latter group also showed more diverse sequence types than the former. Significant differences were only found for virulence genes allS and irp2 between K1 and K2 strains from PLA. Based on the equal virulence factors backgrounds other than serotypes, K2 strain is more virulent than K1 as G. mellonella lethality confirmed. Gene p-rmpA only brings equal virulence to p-rmpA plus p-rmpA2 in K2 strain.Conclusion: Based on the same virulence factors backgrounds except serotypes, K2 K. pneumoniae is more virulent than K1 from PLA, which provides a survival advantage to maintain a stable share.Keywords: Klebsiella pneumoniae, pyogenic liver abscess, serotype, virulence, gene

Yiping Lu,1,&ast; Nan Mei,1,&ast; Yinwei Ying,1,&ast; Dongdong Wang,1 Xuanxuan Li,1 Yajing Zhao,1 Yuqi Zhu,1 Shun Shen,2,3 Bo Yin1 1Department of Radiology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Pharmacy Department, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of China; 3Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Yin; Shun Shen, Email yinbo@fudan.edu.cn; nanocarries@gmail.comAbstract: Surgical removal together with chemotherapy and radiotherapy has used to be the pillars of cancer treatment. Although these traditional methods are still considered as the first-line or standard treatments, non-operative situation, systemic toxicity or resistance severely weakened the therapeutic effect. More recently, synthetic biological nanocarriers elicited substantial interest and exhibited promising potential for combating cancer. In particular, bacteria and their derivatives are omnipotent to realize intrinsic tumor targeting and inhibit tumor growth with anti-cancer agents secreted and immune response. They are frequently employed in synergistic bacteria-mediated anticancer treatments to strengthen the effectiveness of anti-cancer treatment. In this review, we elaborate on the development, mechanism and advantage of bacterial therapy against cancer and then systematically introduce the bacteria-based nanoprobes against cancer and the recent achievements in synergistic treatment strategies and clinical trials. We also discuss the advantages as well as the limitations of these bacteria-based nanoprobes, especially the questions that hinder their application in human, exhibiting this novel anti-cancer endeavor comprehensively. Keywords: bacteria-based nanoprobe, bacteria-mediated synergistic cancer therapy, nanomedicine, tumor targeting, tumor immune microenvironment, clinical trial

Chen Duan,1 Xuemin Yu,2 Xin Feng,1 Li Shi,3 Deyun Wang4 1Department of Otorhinolaryngology, Qilu Hospital of Shandong University, National Health Commission (NHC) Key Laboratory of Otorhinolaryngology, Shandong University, Jinan, Shandong, 250000, People’s Republic of China; 2Department of Otorhinolaryngology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, NHC Key Laboratory of Otorhinolaryngology (Shandong University), Qingdao, Shandong, 250000, People’s Republic of China; 3Department of Otolaryngology, The Second Hospital of Shandong University, Jinan, Shandong, 250000, People’s Republic of China; 4Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeCorrespondence: Li Shi, Department of Otolaryngology, The Second Hospital of Shandong University, Jinan, Shandong, 250000, People’s Republic of China, Email shili126@sina.com Xin Feng, Department of Otorhinolaryngology, Qilu Hospital of Shandong University, National Health Commission (NHC) Key Laboratory of Otorhinolaryngology, Shandong University, Jinan, Shandong, 250000, People’s Republic of China, Email drfengxin@sdu.edu.cnPurpose: Nasal polyp (NP) is characterized by inflammation of the sinonasal mucosa with predominant inflammatory cell infiltration. Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) are recognized to play an important role in leukocyte migration in airway inflammation. Herein, efforts were made to confirm the expression levels of MMPs/TIMPs and study the relationship between the infiltration of inflammatory cells and local expression levels of MMPs/TIMPs in NPs.Patients and Methods: NP tissues were obtained from 42 Chinese patients with bilateral nasal polyps during the endoscopic sinus surgery. Inferior turbinate (IT) tissues from 19 patients with septal deviation were taken during the rhinoplasty surgery as controls. mRNA and protein levels of MMP1, MMP9, MMP10, MMP12, TIMP1 and TIMP3 were assessed by quantitative PCR and immunohistochemistry.Results: Eosinophilia (72%, 23/32 samples), neutrophilia (41%, 13/32 samples), and increase in macrophages (38%, 12/32 samples) were found in NP tissues. mRNA expression of MMP1 (10.9-fold), MMP9 (4.1-fold), MMP10 (6.7-fold) and MMP12 (3.5-fold) were significantly up-regulated, while TIMP1 (1.5-fold) and TIMP3 (6.0-fold) were significantly down-regulated in NPs (n=42) as compared to the controls (n=19). The immunostaining levels of all 4 MMPs and two TIMPs were higher in NPs than those in controls. The co-localization of MMP1/MMP10/MMP12 and macrophages were identified in NPs. MMP9 was mainly expressed in neutrophils, while TIMP1 or TIMP3 were mostly found in eosinophils in NPs.Conclusion: The results of our study indicate that tissue remodeling is significant in NPs, where MMPs/TIMPs play important roles in both tissue remodeling and inflammatory cells infiltration.Keywords: remodeling, inflammatory cells, extracellular matrix, matrix metalloproteinases

Qingcong Zheng,1,&ast; Du Wang,2,&ast; Rongjie Lin,3,&ast; Yuchao Chen,4 Zixing Xu,1 Weihong Xu1 1Department of Orthopedics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 2Arthritis Clinical and Research Center, Peking University People’s Hospital, Beijing, People’s Republic of China; 3Department of Orthopedic Surgery, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 4Department of Paediatrics, Fujian Provincial Hospital South Branch, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zixing Xu; Weihong Xu, Email xuzixing@fjmu.edu.cn; xuweihong815@126.comBackground: Rheumatoid arthritis (RA) is one of the most common chronic inflammatory autoimmune diseases. However, the underlying molecular mechanisms of its pathogenesis are unknown. This study aimed to identify the common biomarkers of ferroptosis and pyroptosis in RA and screen potential drugs.Methods: The RA-related differentially expressed genes (DEGs) in GSE55235 were screened by R software and intersected with ferroptosis and pyroptosis gene libraries to obtain differentially expressed ferroptosis-related genes (DEFRGs) and differentially expressed pyroptosis-related genes (DEPRGs). We performed Gene Ontology (GO), Kyoto Encyclopedia of the Genome (KEGG), ClueGO, and Protein-Protein Interaction (PPI) analysis for DEFRGs and DEPRGs and validated them by machine learning. The microRNA/transcription factor (TF)-hub genes regulatory network was further constructed. The key gene was validated using the GSE77298 validation set, cellular validation was performed in in vitro experiments, and immune infiltration analysis was performed using CIBERSORT. Network pharmacology was used to find key gene-targeting drugs, followed by molecular docking and molecular dynamics simulations to analyze the binding stability between small-molecule drugs and large-molecule proteins.Results: Three hub genes (CASP8, PTGS2, and JUN) were screened via bioinformatics, and the key gene (CASP8) was validated and obtained through the validation set, and the diagnostic efficacy was verified to be excellent through the receiver operating characteristic (ROC) curves. The ferroptosis and pyroptosis phenotypes were constructed by fibroblast-like synoviocytes (FLS), and caspase-8 was detected and validated as a common biomarker for ferroptosis and pyroptosis in RA, and quercetin can reduce caspase-8 levels. Quercetin was found to be a potential target drug for caspase-8 by network pharmacology, and the stability of their binding was further verified using molecular docking and molecular dynamics simulations.Conclusion: Caspase-8 is an important biomarker for ferroptosis and pyroptosis in RA, and quercetin is a potential therapy for RA via targeting caspase-8 through ferroptosis and pyroptosis.Keywords: rheumatoid arthritis, ferroptosis, pyroptosis, caspase-8, quercetin

Dakun Wang,1 Emery Haley,2 Natalie Luke,2 Mohit Mathur,3 Richard A Festa,3 Xinhua Zhao,4 Lori A Anderson,5 Jennifer L Allison,6 Kristen L Stebbins,6 Manuel Jose Diaz,6 David Baunoch7 1Department of Writing, Stat4Ward, Pittsburgh, PA, USA; 2Department of Clinical Research, Pathnostics, Irvine, CA, USA; 3Department of Medical Affairs, Pathnostics, Irvine, CA, USA; 4Department of Statistical Analysis, Stat4Ward, Pittsburgh, PA, USA; 5L. Anderson Diagnostic Market Access Consulting, San Diego, CA, USA; 6DispatchHealth, Denver, CO, USA; 7Pathnostics, Irvine, CA, 92618, USACorrespondence: David Baunoch, Pathnostics, 15545 Sand Canyon Suite 100, Irvine, CA, 92618, USA, Tel +1 714-966-1221, Fax +1 714-966-1231, Email dbaunoch@pathnostics.comIntroduction: This study compared microbial compositions of midstream and catheter urine specimens from patients with suspected complicated urinary tract infections to determine if emerging and fastidious uropathogens are infecting the bladder or are contaminants.Methods: Urine was collected by in-and-out catheter (n = 1000) or midstream voiding (n = 1000) from 2000 adult patients (≥ 60 years of age) at 17 DispatchHealth sites across 11 states. The two groups were matched by age (mean 81 years), sex (62.1% female, 37.9% male), and ICD-10-CM codes. Microbial detection was performed with multiplex polymerase chain reaction (M-PCR) with a threshold for “positive detection” ≥ 10,000 cells/mL for bacteria or any detection for yeast. Results were divided by sex.Results: In females, 28 of 30 microorganisms/groups were found by both collection methods, while in males 26 of 30 were found by both. There were significant overlaps in the detection and densities of classical uropathogens including Escherichia coli, Enterococcus faecalis, and Klebsiella pneumoniae, as well as emerging uropathogens including Actinotignum schaalii and Aerococcus urinae. In females, detection rates were slightly higher in midstream voided compared to catheter-collected (p = 0.0005) urine samples, while males showed the opposite trend (p < 0.0001). More polymicrobial infections were detected in midstream voided compared to catheter-collected samples (64.4% vs 45.7%, p < 0.0001) in females but the opposite in males (35.6% vs 47.0%, p = 0.002).Discussion: In-and-out catheter-collected and midstream voided urine specimens shared significant similarities in microbial detections by M-PCR, with some differences found for a small subset of organisms and between sexes.Conclusion: Non-invasive midstream voided collection of urine specimens for microbial detection and identification in cases of presumed UTI does not result in significantly more contamination compared to in-and-out catheter-collected specimens. Additionally, organisms long regarded as contaminants should be reconsidered as potential uropathogens.Keywords: urinary tract infection, standard urine culture, diagnostic testing, multiplex polymerase chain reaction, catheter, midstream voided