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Tongxin Zhang,1,2 Zilong He,1,2 Yankui Liu,3 Linfang Jin,4 Teng Wang1,2 1Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214122, People’s Republic of China; 2Wuxi Medical College, Jiangnan University, Wuxi, Jiangsu, 214122, People’s Republic of China; 3Department of Pathology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214122, People’s Republic of China; 4Department of Pathology, Wuxi No. 9 People’s Hospital, Wuxi, Jiangsu, 214062, People’s Republic of ChinaCorrespondence: Teng Wang, Department of Oncology, Affiliated Hospital of Jiangnan University, 1000 Hefeng Road, Binhu District, Wuxi, Jiangsu Province, 214000, People’s Republic of China, Tel +8618861530279, Email 9862016033@jiangnan.edu.cnBackground: Anti-claudin (CLDN) 18.2 therapy has been proven to be effective in treating advanced gastric cancer with negative human epidermal growth factor receptor 2 (HER-2). This study purposed to investigate the relationship of CLDN 18.2 expression with prognosis of HER-2-positive gastric cancer patients.Objective: To investigate the expression of claudin (CLDN) 18.2 in Human epidermal growth factor receptor 2 (HER-2) positive gastric cancer patients after radical resection and its relationship with gastric cancer prognosis.Methods: A total of 55 postoperative HER-2-positive gastric cancer patients were included in this study. CLDN 18.2 protein was detected by immunohistochemistry, and detailed clinical and pathological information was collected. Factors considered potentially important in the univariate analysis were included in the multivariate analysis, which involved COX regression to find the independent prognostic factors affecting disease-free survival (DFS).Results: Immunohistochemistry showed that different levels of CLDN 18.2 protein were expressed in HER-2 positive gastric cancer tissues, and the Chi-square analysis showed that the expression level of CLDN 18.2 was significantly correlated with the lymph node stage. Higher expression levels of CLDN 18.2 were found in patients with lymph node positivity and were associated with poor prognosis in HER-2-positive gastric cancer patients. Gastric cancer patients with low and high expressions of CLDN 18.2 had postoperative median DFS of 38.5 months (95% confidence interval (CI) 28.8– 48.2 months) and 12.1 months (95% CI, 11.7– 41.0 months), respectively.Conclusion: High expression of CLDN 18.2 in HER-2 positive gastric cancer is associated with poor prognosis, and the optimal treatment mode for this population is worth exploring after the approval of anti-CLDN 18.2 drugs.Keywords: gastric cancer, HER2, claudin 18.2, prognosis

Yinan Zhao,1 Yan Gu,2 Ying Liu,3 Zhongping Guo4 1Department of Radiology, The Affiliated Jinzhou Medical University, Jinzhou, People’s Republic of China; 2Department of Radiology, The Affiliated First People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China; 3Department of Radiology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, People’s Republic of China; 4Department of Radiology, The Affiliated Lianyungang Clinical College of Nanjing Medical University, Lianyungang, People’s Republic of ChinaCorrespondence: Yan Gu, Department of Radiology, Lianyungang First People’s Hospital, 1st Floor, Building 2, Gaoxin District, No. 6 East Zhenhua Road, Haizhou District, Lianyungang, Jiangsu Province, People’s Republic of China, Tel +86 18961327326, Email 13815617997@139.comPurpose: To analyze the relationship among distribution location, characteristics, and vulnerability of carotid plaque using CTA and provide more information on the risk factors of carotid atherosclerotic plaque.Patients and Methods: We retrospectively analyzed the CTA images of the head and neck of 93 patients with carotid atherosclerosis. Atherosclerosis was developed in 148 carotid arteries. The plaques were divided into a high-risk plaque group and a low-risk plaque group according to whether the plaques had high-risk characteristics. The maximum cross-sectional area of carotid artery bifurcation plaque on the axial image was selected, and the cross-sectional lumen was equally divided into four 90-degree sectors, ventral side wall, dorsal side wall, inner side wall, and outer side wall. The differences in the characteristics and distribution locations of the plaques in the two groups were analyzed. The characteristic parameters of the cross-sectional plaques at the bifurcation of the carotid artery. The logistic regression analysis was used to further analyze the risk factors associated with plaque vulnerability.Results: Among 148 carotid arteries,80 were classified as high-risk and 68 as low-risk groups. There were significant differences between the two groups concerning the thickness, length, maximum cross-sectional area, burden, and cross-sectional distribution of the plaques (P < 0.05). The plaque distribution on the dorsal side wall of the carotid bifurcation was higher in the high-risk group than that in the low-risk group (P < 0.05), dorsal side wall plaque-independent risk factors for the development of vulnerability of plaques in transient ischemic attack (TIA) patients (95% CI:1.522~6.991, P< 0.05).Conclusion: High-risk plaques tend to occur on the dorsal side wall of the carotid bifurcation, whereas low-risk plaques tend to occur on the outer side wall of the carotid bifurcation.Keywords: carotid artery, plaque morphology, plaque vulnerability, atherosclerosis, plaque distribution

Lina Guo,1 Jaclene A Zauszniewski,2 Gege Zhang,1 Xiaoyu Lei,1 Mengyu Zhang,1 Miao Wei,1 Keke Ma,1 Caixia Yang,1 Yanjin Liu,3 Yuanli Guo1 1Department of Neurology, National Advanced Stroke Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, USA; 3Department of Nursing, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Yuanli Guo, Email gylzd@163.comObjective: To explore distinct longitudinal trajectories of resourcefulness among initial ischemic stroke patients from diagnosis to 12 months, and to identify whether sociodemographic factors, disease-related factors, self-efficacy, family function, and social support can predict patterns in the trajectories of resourcefulness.Methods: A prospective longitudinal study was conducted. Initial ischemic stroke patients who met inclusion and exclusion criteria were followed up when still in hospital (Preparing for discharge, Baseline, T1), at 1 month (T2), at 3 months (T3), at 6 months (T4), at 9 months (T5) and 12 months (T6) (± 1 week) after discharge. General information, National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), General Self-Efficacy Scale (GSES), General Family Functioning Subscale (FAD-GF), and Social Support Rate Scale (SSRS) were used in T1. The Resourcefulness Scale© was evaluated at 6 time points. Growth mixture modeling was used to identify trajectory patterns of resourcefulness. Logistic regression was used to identify predictors of resourcefulness trajectories.Results: Three longitudinal trajectories of resourcefulness were identified and named as the high-stable class (38.9%, n=71), fluctuation class (41.2%, n=75), and low-stable class (19.9%, n=36), respectively. Dwelling areas (x2= 6.805, P= 0.009), education (x2= 44.865, P= 0.000), monthly income (x2= 13.063, P= 0.001), NIHSS scores (x2= 44.730, P= 0.000), mRS scores (x2= 51.788, P= 0.000), Hcy (x2= 9.345, P= 0.002), GSES (x2= 56.933, P= 0.000), FAD-GF (x2= 41.305, P= 0.000) and SSRS (x2=52.373, P= 0.000) were found to be statistically significant for distinguishing between different resourcefulness trajectory patterns. Lower education (OR=0.404), higher NIHSS(OR=6.672) scores, and higher mRS(OR=21.418) scores were found to be risk factors for lower resourcefulness, whereas higher education(OR=0.404), GSES(OR=0.276), FAD-GF(OR=0.344), and SSRS(OR=0.358) scores were identified as protective factors enhancing resourcefulness.Conclusion: This study obtained three patterns of trajectories and identified their predictive factors in initial ischemic stroke. The findings will assist health care professionals in identifying subgroups of patients and when they may be at risk of low resourcefulness and provide timely targeted intervention to promote resourcefulness.Keywords: initial ischemic stroke, resourcefulness, longitudinal study, social ecology theory, predictive factors, nursing care

Yanping Guo,1 Zhangbin Yu,2 Huiying Tu,2 Biying Zheng,1 Jiamin Li,1 Ying Liu1 1Department of Pediatrics, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Department of Neonatology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Yanping Guo; Ying Liu, Tel +86-15919990131 ; +86-13902992158, Email guoyanping1223@163.com; 13902992158@139.comBackground and Objectives: To examine the correlation between the concentration of vitamin D (VD) in venous blood at approximately 4 weeks of age (± 4 weeks of age) and neonatal outcomes in preterm infants (birth weight < 1500 g or gestational age < 32 weeks) in two neonatal intensive care units (NICUs) located in Shenzhen, China.Methods and Study Design: Preterm infants were split into two groups based on their VD concentration at ± 4 weeks of age: VD insufficiency (VDI) group (≤ 20 ng/mL) and VD sufficient (VDS) group (> 20 ng/mL). Binary logistic regression analysis was used to examine relationships between outcomes and VDI.Results: Of 230 infants in total, 119 (51.7%) were assigned to the VDI group and 111 to the VDS group (48.3%). No correlation was found between serum VD at ± 4 weeks of age and gestational age (p> 0.05). The starting point of the two groups for oral VD intake did not differ significantly (p> 0.05). At ± 4 weeks of age, oral VD dose (P< 0.05) was greater in the VDS group. Gestational diabetes mellitus was associated with VDI (OR=1.94, 95% CI 1.01– 3.75, p=0.047) after controlling for this risk. Following correction for gestational age and oral VD dosage at ± 4 weeks old, VDI was also linked to a significant risk of retinopathy of prematurity (OR=2.00, 95% CI 1.08– 3.68, p< 0.027).Conclusion: Preterm newborns (gestational age < 32 weeks or birth age < 1500 g) in NICUs in Shenzhen, China continue to have significantly high VDI. Higher VDI is associated with gestational diabetes mellitus and retinopathy of prematurity.Keywords: very preterm birth, very low birth weight infant, vitamin D, 4 weeks of age, outcome

Yuanyuan Zhao,1 Yang Liu,1 Cheng Lu,1 Daokuan Sun,2 Shiqi Kang,1 Xin Wang,2,&ast; Laijin Lu1,&ast; 1Department of Hand and Podiatric Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2School of Materials Science and Engineering, Jilin University, Changchun, Jilin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Laijin Lu, Department of Hand and Podiatric Surgery, Orthopedics Center, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China, Tel +86-13756661203, Fax +86 431 84808391, Email ljlu@jlu.edu.cn Xin Wang, School of Materials Science and Engineering, Jilin University, Changchun, Jilin, People’s Republic of China, Tel +86-18 626 655 395, Fax +86 431 84 808 391, Email wang_xin@jlu.edu.cnBackground: The treatment of long-gap peripheral nerve injury (PNI) is still a substantial clinical problem. Graphene-based scaffolds possess extracellular matrix (ECM) characteristic and can conduct electrical signals, therefore have been investigated for repairing PNI. Combined with electrical stimulation (ES), a well performance should be expected. We aimed to determine the effects of reduced graphene oxide fibers (rGOFs) combined with ES on PNI repair in vivo.Methods: rGOFs were prepared by one-step dimensionally confined hydrothermal strategy (DCH). Surface characteristics, chemical compositions, electrical and mechanical properties of the samples were characterized. The biocompatibility of the rGOFs were systematically explored both in vitro and in vivo. Total of 54 Sprague-Dawley (SD) rats were randomized into 6 experimental groups: a silicone conduit (S), S+ES, S+rGOFs-filled conduit (SGC), SGC+ES, nerve autograft, and sham groups for a 10-mm sciatic defect. Functional and histological recovery of the regenerated sciatic nerve at 12 weeks after surgery in each group of SD rats were evaluated.Results: rGOFs exhibited aligned micro- and nano-channels with excellent mechanical and electrical properties. They are biocompatible in vitro and in vivo. All 6 groups exhibited PNI repair outcomes in view of neurological and morphological recovery. The SGC+ES group achieved similar therapeutic effects as nerve autograft group (P > 0.05), significantly outperformed other treatment groups. Immunohistochemical analysis showed that the expression of proteins related to axonal regeneration and angiogenesis were relatively higher in the SGC+ES.Conclusion: The rGOFs had good biocompatibility combined with excellent electrical and mechanical properties. Combined with ES, the rGOFs provided superior motor nerve recovery for a 10-mm nerve gap in a murine acute transection injury model, indicating its excellent repairing ability. That the similar therapeutic effects as autologous nerve transplantation make us believe this method is a promising way to treat peripheral nerve defects, which is expected to guide clinical practice in the future.Keywords: peripheral nerve defects, sciatic nerve injury, functional recovery, tissue engineering, conductive materials

Ke Ma,1,&ast; Zhixiang Cheng,2,&ast; Hao Jiang,3,&ast; Zhangya Lin,4,&ast; Chuansheng Liu,5,&ast; Xianguo Liu,6,&ast; Lijuan Lu,7,&ast; Yan Lu,8,&ast; Wei Tao,9,&ast; Suoliang Wang,10,&ast; Xiaoqiu Yang,11,&ast; Qishan Yi,12,&ast; Xiaomei Zhang,13,&ast; Ying Zhang,14,&ast; Yanqing Liu15,&ast; 1Department of Algology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Algology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Algology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 5Department of Algology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 6Pain Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 7Department of Pain Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 8Department of Algology, Xijing Hospital, The Fourth Military Medical University, Xian, People’s Republic of China; 9Department of Neurosurgery, Shenzhen University General Hospital, Shenzhen, People’s Republic of China; 10Department of Algology, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 11Department of Algology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 12Department of Algology, The Yibin First People’s Hospital Affiliated Chongqing Medical University, Yibin, People’s Republic of China; 13Department of Algology, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 14Department of Algology. Hospital (T.C.M) Affiliated to Southwest Medical University, Luzhou, People’s Republic of China; 15Department of Algology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Ma, Department of Algology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University school of medicine, Shanghai, 200092, People’s Republic of China, Tel +86133618792160, Email marke72@163.com Yanqing Liu, Department of Algology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China, Tel +8618601203409, Email lyqttyy@126.comAbstract: Ion channel drugs have been increasing used for chronic pain management with progress in the development of selective calcium channel modulators. Although ion channel drugs have been proven safe and effective in clinical practice, uncertainty remains regarding its use to treat chronic pain. To standardize the clinical practice of ion channel drug for the treatment of chronic pain, the National Health Commission Capacity Building and Continuing Education Center for Pain Diagnosis and Treatment Special Ability Training Project established an expert group to form an expert consensus on the use of ion channel drugs for the treatment of chronic pain after repeated discussions on existing medical evidence combined with the well clinical experience of experts. The consensus provided information on the mechanism of action of ion channel drugs and their recommendations, caution use, contraindications, and precautions for their use in special populations to support doctors in their clinical decision-making.Keywords: chronic pain, ion channel drugs, voltage-gated calcium channels, voltage-gated sodium channel

Taotao Sun,1 Yipiao Liu,2 Penghui Yuan,1 Zhankui Jia,1 Jinjian Yang1 1Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China; 2Department of Hepatopancreatobiliary Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Taotao Sun; Jinjian Yang, Department of Urology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China, Email suntt94@163.com; yangjinjian2011@126.comPurpose: As a common male disease, erectile dysfunction (ED) seriously affects the physical and mental health of patients. In recent years, studies have continued to point out the great potential of stem cell therapy (SCT) in the treatment of ED. The purpose of this study is to comprehensively analyze the research of SCT for ED and understand the development trends and research frontiers in this field.Methods: Publications regarding SCT and ED were retrieved and collected from the Web of Science Core Collection. CiteSpace and VOSviewer software were then utilized for bibliometric and visualization analysis.Results: A total of 524 publications were eventually included in this study. The annual number of publications in this field was increasing year by year. China and the USA were the two most productive countries. Lin GT, Lue TF and Lin CS, and the University of California San Francisco where they worked were the most productive research group and institution, respectively. The journal with the largest number of publications was The Journal of Sexual Medicine, and the following were mostly professional journals of urology and andrology. Diabetes mellitus-induced ED and cavernous nerve injury-related ED were the two most commonly constructed models of ED in studies. Concerning the types of stem cells, mesenchymal stem cells derived from adipose and bone marrow were most frequently used. Moreover, future research would mainly focus on exosomes, tissue engineering technology, extracorporeal shockwave therapy, and clinical translation.Conclusion: The research of SCT for ED will receive increasing global attention in the future. Our study provided bibliometric and visualization analysis of published literature, helping researchers understand the global landscape and frontiers in this field. More preclinical and clinical studies should be conducted to more deeply explore the underlying mechanisms of treatment and promote clinical translation.Keywords: erectile dysfunction, stem cells, bibliometric analysis, visualization, VOSviewer, citespace

Xinting Wang,1,&ast; Jiahui Yang,1,&ast; Cheng Lu,2 Yinqin Hu,1 Zhaohui Xu,1 Qiqi Wan,1 Meng Zhang,1 Tianyun Shi,1 Zhirui Liu,1 Yongming Liu1 1Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, People’s Republic of China; 2Department of Cardiology, Seventh People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200137, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongming Liu, Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No. 185, Pu’an Road, Huangpu District, Shanghai, 200021, People’s Republic of China, Email liuyongming@foxmail.comPurpose: This study aimed to elucidate the protective mechanism of Traditional Chinese Medicine (TCM) Qifu Yixin formula (QFYXF) to improve heart failure (HF) by promoting β-arrestin2 (β-arr2)-mediated SERCA2a SUMOylation.Materials and Methods: The transverse aortic constriction (TAC)-induced HF mice were treated with QFYXF or carvedilol for 8 weeks. β-arr2-KO mice and their littermate wild-type (WT) mice were used as controls. Neonatal rat cardiomyocytes (NRCMs) were used in vitro. Cardiac function was evaluated by echocardiography and serum NT-proBNP. Myocardial hypertrophy and myocardial fibrosis were assessed by histological staining. β-arr2, SERCA2a, SUMO1, PLB and p-PLB expressions were detected by Western blotting, immunofluorescence and immunohistochemistry. SERCA2a SUMOylation was detected by Co-IP. The molecular docking method was used to predict the binding ability of the main active components of QFYXF to β-arr2, SERCA2a, and SUMO1, and the binding degree of SERCA2a to SUMO1 protein.Results: The HF model was constructed 8 weeks after TAC. QFYXF ameliorated cardiac function, inhibiting myocardial hypertrophy and fibrosis. QFYXF promoted SERCA2a expression and SERCA2a SUMOylation. Further investigation showed that QFYXF promoted β-arr2 expression, whereas Barbadin (β-arr2 inhibitor) or β-arr2-KO reduced SERCA2a SUMOylation and attenuated the protective effect of QFYXF improved HF. Molecular docking showed that the main active components of QFYXF had good binding activities with β-arr2, SERCA2a, and SUMO1, and SERCA2a had a high binding degree with SUMO1 protein.Conclusion: QFYXF improves HF by promoting β-arr2 mediated SERCA2a SUMOylation and increasing SERCA2a expression.Keywords: heart failure, Qifu Yixin Formula, β-arrestin2, SERCA2a, SUMOylation

Ye Liu,1,&ast; Lifan Zhang,1– 4,&ast; Yan Chen,1,&ast; Guiren Ruan,1– 3 Yuchen Liu,1 Shi Chen,1 Lantian Xie,1 Fengying Wu,1 Xiaochun Shi,1– 3 Xiaoqing Liu1– 4 1Division of Infectious Diseases, Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 3Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Clinical Epidemiology Unit, Peking Union Medical College, International Clinical Epidemiology Network, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaochun Shi; Xiaoqing Liu, Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan No. 1, Beijing, 100005, People’s Republic of China, Email shixch7722@163.com; liuxq@pumch.cnBackground: The population with latent tuberculosis infection (LTBI) represents a potential pool of patients with active tuberculosis (ATB). T-SPOT.TB is an important test tool for screening LTBI. Owing to the large population of LTBI patients in China, it is necessary to identify a high-risk group for LTBI and enlarge tuberculosis preventive treatment (TPT) to reduce the incidence of ATB.Methods: Hospitalized patients with positive T-SPOT.TB results were recruited from January 2013 to December 2016. Patients with ATB were excluded. Basic information was collected and the development of ATBs was examined during follow-up. The life-table method was used to calculate cumulative incidence rates. Potential risk factors were analyzed through Cox regression analysis.Results: A total of 1680 patients with LTBI were recruited in the follow-up cohort, and 377 (22.44%) patients dropped out. With a median follow-up time of 81 months [interquartile range (IQR):61– 93], 19 of 1303 patients with LTBI developed ATB. The 1-year incidence of ATB was 614 per 100,000 individuals [95%confidence interval (95% CI):584– 644]. Over 5-year period, the cumulative incidence of ATB was 1496 per 100,000 [95% CI:1430– 1570], and the incidence density was 240 per 100,000 person-years[95% CI:144– 375]. In the Cox regression model, exposure of pulmonary tuberculosis (PTB) [adjusted hazard ratio (aHR)=10.557, 95% CI:2.273– 49.031], maximum daily dosage of glucocorticoids (GCs)≥ 50 mg/d (aHR=2.948, 95% CI:1.122– 7.748), leflunomide (LEF) treatment (aHR=8.572, 95% CI:2.222 − 33.070), anemia (aHR=2.565, 95% CI:1.015– 6.479) and T-SPOT.TB level≥ 300SFCs/106 PBMCs (aHR=4.195, 95% CI:1.365– 12.892) were independent risk factors for ATB development in LTBI patients.Conclusion: The incidence of ATB is significantly higher in hospitalized patients with LTBI than in the general population. The exposure history of PTB, maximum daily dosage of GCs≥ 50 mg/day, LEF treatment, anemia, and T-SPOT.TB level≥ 300SFCs/106PBMCs, were the risk factors of tuberculosis reactivation. Hospitalized LTBI patients with the above factors may need TPT.Keywords: latent tuberculosis infection, active tuberculosis, incidence, risk factors

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

Yanhan Liu School of Education, University of Glasgow, Glasgow, UKCorrespondence: Yanhan Liu, Email meigong516972@163.comIntroduction: Resilience, a pivotal construct in positive psychology, remains incompletely understood in its facilitation of learners’ online engagement. This study aims to investigate the relationship between resilience, transactional distance, and Online Mathematics Learning Engagement (OMLE) among first-year university students.Methods: Utilizing a cross-lagged path analysis approach, the study surveyed 612 first-year students. Multiple models were constructed and compared to explore the mutual predictive relationships between resilience, transactional distance, and OMLE.Results: Among the compared models, Model 4 demonstrated the best fit. The model revealed that: (1) resilience at Time 1 and Time 2 positively predicted transactional distance at Time 2 and Time 3; (2) transactional distance at Time 1 and Time 2 positively predicted OMLE at Time 2 and Time 3; (3) resilience at Time 1 significantly predicted OMLE at Time 3; and (4) transactional distance at Time 2 fully mediated the relationship between resilience at Time 1 and OMLE at Time 3. Furthermore, mediational model analysis confirmed that transactional distance played a mediating role in the longitudinal relationship between resilience and OMLE. Using a cross-lagged mediational model with 5000 bootstrap samples, the indirect effect of transactional distance on the relationship between resilience at Time 1 and OMLE at Time 3 was significant and remained stable over time.Discussion: The findings suggest that resilience, as a positive psychological resource, stimulates students to seek and utilize protective resources in online environments, leading to more active participation in interpersonal communication and classroom interactions. Additionally, resilience helps students overcome emotional and practical difficulties encountered in online learning, thereby enhancing their OMLE. These insights offer valuable implications for educators, highlighting the potential to improve students’ online learning engagement by fostering their psychological resilience.Keywords: psychological resilience, transactional distance theory, online mathematics learning engagement, cross-lag model, university students

Yi Liu,1 David Quintanar Guerrero,2 David Lechuga-Ballesteros,3 Mingdian Tan,1 Faiz Ahmad,1 Bilal Aleiwi,4 Edmund Lee Ellsworth,4 Bin Chen,4 Mei-Sze Chua,1 Samuel So1 1Department of Surgery, School of Medicine, Stanford University, Stanford, CA, USA; 2Laboratorio de Investigación y Posgrado en Tecnologías Farmacéuticas, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Cuautitlán Izcalli, CP, 54745, Mexico; 3AstraZeneca Pharmaceuticals, Ltd. 4222 Emperor Boulevard, Durham, NC, USA; 4Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USACorrespondence: Mei-Sze Chua, Email mchua@stanford.eduIntroduction: We previously identified niclosamide as a promising repurposed drug candidate for hepatocellular carcinoma (HCC) treatment. However, it is poorly water soluble, limiting its tissue bioavailability and clinical application. To overcome these challenges, we developed an orally bioavailable self-microemulsifying drug delivery system encapsulating niclosamide (Nic-SMEDDS).Methods: Nic-SMEDDS was synthesized and characterized for its physicochemical properties, in vivo pharmacokinetics and absorption mechanisms, and in vivo therapeutic efficacy in an orthotopic patient-derived xenograft (PDX)-HCC mouse model. Niclosamide ethanolamine salt (NEN), with superior water solubility, was used as a positive control.Results: Nic-SMEDDS (5.6% drug load) displayed favorable physicochemical properties and drug release profiles in vitro. In vivo, Nic-SMEDDS displayed prolonged retention time and plasma release profile compared to niclosamide or NEN. Oral administration of Nic-SMEDDS to non-tumor bearing mice improved niclosamide bioavailability and Cmax by 4.1- and 1.8-fold, respectively, compared to oral niclosamide. Cycloheximide pre-treatment blocked niclosamide absorption from orally administered Nic-SMEDDS, suggesting that its absorption was facilitated through the chylomicron pathway. Nic-SMEDDS (100 mg/kg, bid) showed greater anti-tumor efficacy compared to NEN (200 mg/kg, qd); this correlated with higher levels (p < 0.01) of niclosamide, increased caspase-3, and decreased Ki-67 in the harvested PDX tissues when Nic-SMEDDS was given. Biochemical analysis at the treatment end-point indicated that Nic-SMEDDS elevated lipid levels in treated mice.Conclusion: We successfully developed an orally bioavailable formulation of niclosamide, which significantly enhanced oral bioavailability and anti-tumor efficacy in an HCC PDX mouse model. Our data support its clinical translation for the treatment of solid tumors.Keywords: niclosamide, self-microemulsifying drug delivery system, SMEDDS, oral bioavailability, drug repurposing, hepatocellular carcinoma

Rui Jing,1 Hui Dong,1 Kun Huang,2 Zhong Liu,1 Ran Xue,1 Yiran Dong,1 Mei Jiao,3 Na Li,4 Yumei Guo,5 Yun Liu,6 Wenqian Zhang,1 Hongyun Sun1 1Institute for Tuberculosis Control, Jinan Center for Disease Control and Prevention, Jinan, People’s Republic of China; 2Tuberculosis Control Division, Licheng Center for Disease Control and Prevention, Jinan, People’s Republic of China; 3Department of Sexually Transmitted Diseases and AIDS Prevention and Control, Lixia Center for Disease Control and Prevention, Jinan, People’s Republic of China; 4Tuberculosis and Vector Control Division, Shizhong Center for Disease Control and Prevention, Jinan, People’s Republic of China; 5Department of Infectious Diseases and Endemic Disease Control, Huaiyin Center for Disease Control and Prevention, Jinan, People’s Republic of China; 6AIDS Prevention and Control Department, Tianqiao Center for Disease Control and Prevention, Jinan, People’s Republic of ChinaCorrespondence: Wenqian Zhang; Hongyun Sun, Institute for Tuberculosis Control, Jinan Center for Disease Control and Prevention, Jinan, People’s Republic of China, Tel +86 0531-81278897 ; +86 0531 81278873, Email wqzh618@gmail.com; jncdcxxtb@jn.shandong.cnPurpose: This study aimed to investigate awareness of tuberculosis control among post-treatment tuberculosis patients, in order to provide a basis for future preventive and control work in this population.Patients and Methods: A cross-sectional descriptive study was conducted on post-treatment patients with tuberculosis in seven districts of Jinan City between July 2021 and December 2022. A face-to-face or telephone interviews using structured questionnaires for the research subjects were conducted by data collectors. Analyses were carried out first for all subjects, and then separately for male and female subjects.Results: A total of 837 valid questionnaires were collected, of which 495 were males and 342 were females. The awareness rate of the core TB knowledge was 82.46%. The ≥ 65 year group in the total group (OR=0.43, 95% CI: (0.28, 0.68)), male (OR=0.47, 95% CI: (0.27, 0.83)) and female group (OR=0.40, 95% CI: (0.19, 0.86)) was lower than that of the control group. Educational level and monthly income are the main factors of TB cognition in total group. People with university or higher education (OR=2.05, 95% CI: (1.38, 3.05)) and with a monthly income of ≥ 6,000 (OR=1.89, 95% CI: (1.10, 3.25)) had a higher awareness rate. The group with current residence in the city was more aware than the reference group.Conclusion: In the future, the communication of the main transmission route, suspicious symptoms, and cure of TB needs to be strengthened for the post-treatment TB patients. The elderly, those with secondary school education or below, agricultural workers and low-income people are the groups with weak knowledge of TB, and they are also the groups that need to be focused on health education. The above information should be focused on the above groups of people in order to educate them in a way that is easily acceptable to them.Keywords: pulmonary tuberculosis, awareness rate, completed treatment patients, layered analysis

Kaifang Yao,1,&ast; Zhihan Chen,1,&ast; Yanwei Li,1 Baomin Dou,1 Zhifang Xu,1– 3 Yajing Ma,1 Simin Du,1 Jiangshan Wang,1 Jiangjiang Fu,1 Qi Liu,1 Zezhi Fan,1 Yangyang Liu,1– 3 Xiaowei Lin,1– 3 Yuan Xu,1– 3 Yuxin Fang,1– 3 Shenjun Wang,1– 3 Yi Guo1,3,4 1Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin City, People’s Republic of China; 2School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin City, People’s Republic of China; 3National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin City, People’s Republic of China; 4School of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Guo; Shenjun Wang, School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, No. 10 Poyang Lake Road, Tuanbo New Town, Jinghai District, Tianjin, 301617, People’s Republic of China, Tel +86 22-5959-6290, Email guoyi_168@163.com; shenjunwang@163.comPurpose: Acupuncture (ACU) has been demonstrated to alleviate inflammatory pain. Mechanoreceptors are present in acupuncture points. When acupuncture exerts mechanical force, these ion channels open and convert the mechanical signals into biochemical signals. TRPA1 (T ransient receptor potential ankyrin 1) is capable of sensing various physical and chemical stimuli and serves as a sensor for inflammation and pain. This protein is expressed in immune cells and contributes to local defense mechanisms during early tissue damage and inflammation. In this study, we investigated the role of TRPA1 in acupuncture analgesia.Patients and Methods: We injected complete Freund’s adjuvant (CFA) into the mouse plantars to establish a hyperalgesia model. Immunohistochemistry and immunofluorescence analyses were performed to determine the effect of acupuncture on the TRPA1 expression in the Zusanli (ST36). We used TRPA1−/− mouse and pharmacological methods to antagonize TRPA1 to observe the effect on acupuncture analgesia. On this basis, collagenase was used to destroy collagen fibers at ST36 to observe the effect on TRPA1.Results: We found that the ACU group vs the CFA group, the number of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 increased significantly. In CFA- inflammatory pain models, the TRPA1−/− ACU vs TRPA1+/+ ACU groups, the paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) downregulated significantly. In the ACU + high-, ACU + medium-, ACU + low-dose HC-030031 vs ACU groups, the PWL and PWT were downregulated, and in carrageenan-induced inflammatory pain models were consistent with these results. We further found the ACU + collagenase vs ACU groups, the numbers of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 were downregulated.Conclusion: These findings together imply that TRPA1 plays a significant role in the analgesic effects produced via acupuncture at the ST36. This provides new evidence for acupuncture treatment of painful diseases.Keywords: acupuncture, TRPA1, ST36, inflammation, immune, analgesia

Yufeng Ling,1 Menglu Duan,1 Wen Lyu,1 Jie Yang,1,2 Yu Liu,1,3 Shuangshuang Ren,1,4 Wenlei Wu1,3 1Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of China; 2Department of Periodontology, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of China; 3Department of Senior Specialist, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of China; 4Department of Cariology and Endodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of ChinaCorrespondence: Wenlei Wu; Shuangshuang Ren, Tel +025-83620252 ; +025-83620215, Email wlwu@nju.edu.cn; zjndrenss@163.comIntroduction: Periodontitis, a chronic inflammatory disease prevalent worldwide, is primarily treated through GTR for tissue regeneration. The efficacy of GTR, however, remains uncertain due to potential infections and the intricate microenvironment of periodontal tissue. Herein, We developed a novel core-shell structure multifunctional membrane using a dual-drug-loaded coaxial electrospinning technique (Lys/ACP-CNF), contains L-lysine in the outer layer to aid in controlling biofilms after GTR regenerative surgery, and ACP in the inner layer to enhance osteogenic performance for accelerating alveolar bone repair.Methods: The biocompatibility and cell adhesion were evaluated through CCK-8 and fluorescence imaging, respectively. The antibacterial activity was assessed using a plate counting assay. ALP, ARS, and RT-qPCR were used to examine osteogenic differentiation. Additionally, an in vivo experiment was conducted on a rat model with acute periodontal defect and infection. Micro-CT and histological analysis were utilized to analyze the in vivo alveolar bone regeneration.Results: Structural and physicochemical characterization confirmed the successful construction of the core-shell fibrous structure. Additionally, the Lys/ACP-CNF showed strong antibacterial coaggregation effects and induced osteogenic differentiation of PDLSCs in vitro. The in vivo experiment confirmed that Lys/ACP-CNF promotes new bone formation.Conclusion: Lys/ACP-CNF rapidly exhibited excellent antibacterial activity, protected PDLSCs from infection, and was conducive to osteogenesis, demonstrating its potential application for clinical periodontal GTR surgery. Keywords: anti-microbial therapy, L-lysine, electrospun membrane, osteogenic, periodontal tissue regeneration

Yue Wang,&ast; Liyan Chu,&ast; He Li, Yingjie Du, Shanshan Wang, Ying Liu, Guyan Wang Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guyan Wang, Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaominxiang, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-13910985139, Email guyanwang2006@163.comPurpose: The aim of this study was to determine whether preoperative video distraction reduces the incidence of emergence delirium in preschool children under general anesthesia with sevoflurane.Patients and Methods: In this prospective randomized controlled study, children aged 3– 6 years were randomized to receive either video distraction (Group V) or common clinical practice (Group C) from arrival at the holding area to induction of anesthesia. The primary outcome was the incidence of emergence delirium. Preoperative anxiety scores, assessed by the simple modified Yale Perioperative Anxiety Scale, were also collected.Results: A total of 160 patients were included in our study. The children in Group V (n=80) exhibited a significantly lower incidence of emergence delirium than did those in Group C (n=80) (12.5% vs 35.0%; RR 0.36, 95% CI 0.19, 0.69; P =0.0008). The maximum Pediatric Anesthesia Emergence Delirium score in Group V was significantly lower than that in Group C (3.0 vs 5.0; mean difference − 2.64, 95% CI: − 4.12, − 1.16; P=0.0003). The simple modified Yale Perioperative Anxiety Scale scores at separation from parents and the onset of inhalation induction in Group V were significantly lower than those in Group C (36.4 ± 9.9 vs 48.2 ± 16.7; mean difference 11.92, 95% CI 7.25, 16.59; P< 0.0001 and 41.5 ± 15.9 vs 59.7 ± 21.5; mean difference 18.11, 95% CI 11.76, 24.47; P< 0.0001).Conclusion: Preoperative video distraction reduces the incidence of emergence delirium in preschool children who undergo strabismus surgery under general anesthesia with sevoflurane.Keywords: emergence delirium, anxiety, children, preschool

Congcong Wang,1,&ast; Jinyu Xiang,1,&ast; Qingyu Zhang,1 Jing Li,1 Yanqing Liu,2 Jiannan Liu1 1Department of Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shangdong, 264000, People’s Republic of China; 2Department Brest Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shangdong, 264000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiannan Liu, Department of Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20 Yuhuangding East Road, Yantai, 264000, People’s Republic of China, Email ljnwcc@163.com Yanqing Liu, Department Brest Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20 Yuhuangding East Road, Yantai, 264000, People’s Republic of China, Email liuyanqing927@163.comAim: Approximately 50% of patients diagnosed with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (BC) are estimated to develop brain metastases (BMs). This study was aimed to assess the intracranial efficacy and survival benefits of pyrotinib and capecitabine combination therapy in the treatment of BMs in patients with HER2-positive BC.Methods: A total of 56 HER2-positive BC patients with BMs were treated with 400 mg pyrotinib once daily along with 1000 mg/m2 capecitabine twice daily for 14 days in 21-day cycles. The patients were allocated into three cohorts: (1) Cohort A composed of patients with newly diagnosed BMs without prior local radiotherapy, (2) Cohort B included patients with stable post-local radiotherapy, and (3) Cohort C composed of patients with progression following local radiotherapy. The primary endpoint was the intracranial objective response rate (CNS-ORR), while secondary endpoints included intracranial disease control rate (CNS-DCR), progression-free survival (PFS), overall survival (OS), safety, as well as QoL.Results: The observed CNS-ORR CNS-ORR of 72.73% (95% CI 51.85– 86.85%) in cohort A, 55% (95% CI 34.21– 74.18%) in cohort B, and 42.86% (95% CI 21.38– 67.41%) in cohort C. The mPFS was 11 months, 8.4 months, and 5.2 months in cohorts A, B, and C, respectively. Diarrhea, accounting for 23.21% of all the patients, was the most common grade 3/4 adverse event related with treatments (6/22 [27.3%] in cohort A, 4/20 [20.0%] in cohort B, and 3/14 [21.4%] in cohort C). However, there were no deaths related with treatments observed. Importantly, the QoL was efficiently maintained throughout the treatment duration.Conclusion: Pyrotinib and capecitabine combination therapy proved significant effectiveness as well as tolerability in treating HER2-positive BC with BMs, yielding satisfactory results, especially in radiotherapy-naive population.Keywords: breast cancer, brain metastases, pyrotinib, capecitabine, HER2, radiotherapy

Kun Cao,1,2,&ast; Zehui Wang,1,3,5,6,&ast; Xiaojiao Sun,3– 6,&ast; Di Yan,1– 3 Yanwen Liu,3 Ting Ma,3 Xiaojuan Sun1,2 1Department of Oral and Maxillofacial Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 2Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 3School of Stomatology, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 4Animal Experiment Center of Ningxia Medical University, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 5Stem Cell Institute, General Hospital, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 6Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zehui Wang, Department of Oral and Maxillofacial Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China, Email wangzehui364@163.com Xiaojuan Sun, Department of Oral and Maxillofacial Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China, Email ms_sunxiaojuan@126.comIntroduction: Nano-mesoporous bioactive glass and RGD peptide-coated collagen membranes have great potential in wound healing. However, the application of their compound has not been further studied. Our purpose is to prepare a novel bioactive collagen scaffold containing both NMBG stent and adhesion peptides (BM), which then proves its promising prospect the assessment of physical properties, biocompatibility, GSK-3β/β-catenin signaling axis and toxicological effects.Methods: The structural and morphological changes of BM were analyzed using scanning electron microscopy (SEM) and Energy Dispersive Spectroscopy (EDS). In vivo, wound healing of BM was assessed in SD rats through dynamic monitoring and calculation of wound healing rate. Immunohistofluorescence (IHF), H&E, and Masson staining were utilized; in vitro, primary cell culture, and a variety of assays including CCK-8, Transwell, Scratch, Immunocytofluorescence (ICF), and Western blot (WB) were performed, both for morphology and molecular analysis.Results and Discussion: Preparation of BM involved attaching NMBG to RGD-exposed collagen while avoiding the use of toxic chemical reagents. BM exhibited a distinctive superficial morphology with increased Si content, indicating successful NMBG attachment. In vivo studies on SD rats demonstrated the superior wound healing capability of BM, as evidenced by accelerated wound closure, thicker epithelial layers, and enhanced collagen deposition compared to the NC group. Additionally, BM promoted skin fibroblast migration and proliferation, possibly through activation of the GSK-3β/β-catenin signaling axis, which was crucial for tissue regeneration. This study underscored the potential of BM as an effective wound-healing dressing.Conclusion: A new method for synthesizing ECM-like membranes has been developed using nano-mesoporous bioactive glass and collagen-derived peptides. This approach enhances the bioactivity of biomaterials through surface functionalization and growth factor-free therapy.Keywords: NMBG, proliferation, RGD, migration, wound healing, GSK-3β/β-catenin signaling axis

Mei Xiao,1 Guangwen Luo,1 Zhaowei Zhang,1 Yanfen Liu,2 Rui Gong,3 Jianghuan Ke1 1Department of Pharmacy, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of China; 2Department of Endocrinology and Metabolism, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of China; 3Department of Clinical Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of ChinaCorrespondence: Guangwen Luo, Department of pharmacy, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, 321000, People’s Republic of China, Tel +86-0579-82552760, Email lgw2018@126.comPurpose: To investigate the correlation between thyroid-related hormones and diabetic retinopathy (DR) in euthyroid patients with type 2 diabetes mellitus (T2DM).Patients and Methods: Patients with T2DM admitted to our hospital between January 2023 and June 2023 were retrospectively analyzed. The patients were divided into DR and non-diabetic retinopathy (NDR) groups according to whether DR occurred. Thyroid function-related hormones (TSH, FT3, and FT4), blood glucose indices (FBG and HbA1c), and blood lipid indices (HDL-C, LDL-C, TC, and TG) of the two groups were analyzed by univariate and multivariate logistic regression to explore the risk factors for DR. Pearson correlation analysis and multiple stepwise regression analysis were used to investigate the correlation of TSH or FT3 with FBG, HbA1c, and TG in DR patients.Results: Of the 286 patients with T2DM included in this study, 101 (35.31%) developed DR and 185 (64.69%) did not. High TG, FBG, HbA1c, and TSH and low FT3 levels were independent risk factors for DR in T2DM patients. TSH positively correlated with TG, whereas FT3 negatively correlated with TG and HbA1c in T2DM patients with DR.Conclusion: Higher TSH and lower FT3 in T2DM patients with normal thyroid function may affect glucose and lipid metabolism, thereby increasing the risk of DR.Keywords: type 2 diabetes mellitus, diabetic retinopathy, thyroid-stimulating hormone, free triiodothyronine, glucose and lipid metabolism

Yan Liu, Yang Li, Song Yuan, Wei Ma, Si Chen, Li-Yi Wang Department of Infection Control, the Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of ChinaCorrespondence: Li-Yi Wang, Department of Infection Control, the Second Hospital of Hebei Medical University, No. 215 of Heping West Road; Xinhua District, Shijiazhuang, Hebei, 050000, People’s Republic of China, Tel +86 13673160996, Fax +86 0311 83179721, Email wangliyi66@163.comObjective: To examine the risk factors linked with occupational blood exposure (OBE) among nursing staff (NS), we pinpoint deficiencies in the compliance with policies of infection prevention and control, and assess the expenditures associated with infection prevention and control.Methods: Healthcare workers that completed an “Occupational Blood Exposure Report Form” were divided into NS (observation) group and non-NS (control) group. Univariate and multivariable analyses were conducted to compare both groups in various aspects. We also explored design patents intended to minimize occupational exposure.Results: The highest incidence of OBE was observed in the department of neurosurgery. Among NS, OBE incidence was found to be influenced by independent risk factors, such as gender, age, occupational title, work location, and incidence of sharps injuries. Protective factors against OBEs included the use of arterial blood gas needles and suture needles. Personal protective equipment (PPE) usage rates were low in both groups prior to OBEs (0.74% vs 0.00%, P > 0.05). Correct emergency management could be improved promptly by both groups following an OBE (P > 0.05). However, the observation group exhibited a higher proportion of blood expression after a sharps injury and a higher re-evaluation rate at 6 months post-exposure compared to the control group (P < 0.05). In 2018, the per capita costs of infection prevention and control for NS were the Chinese Yuan (RMB) 339.43 per individual. In response to these findings, two utility model patents have been authorized.Conclusion: The risk and protective factors related to the occurrence of OBEs were investigated in this study, suggesting that there is a need for improvement in the rate of PPE usage and the re-evaluation rate of OBEs among NS. Additionally, focused training on emergency blood expression and compliance with policies among non-NS personnel is deemed necessary.Keywords: compliance, infection prevention and control, nursing staff

Yubin Zhu,1 Yilu Zhuang,2 Yawen Yu,2 Jinyue Wang,2 Yongtai Liu,3 Zhi Ruan,2,4 Wei Xiao,5 Yingying Kong2,4 1Department of Gastroenterology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3The First Division Hospital of XinJiang Production and Construction Group, XinJiang, People’s Republic of China; 4Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, People’s Republic of China; 5Department of Emergency Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Yingying Kong; Wei Xiao, Email kongyy@zju.edu.cn; Xiaowei 2022@zju.edu.cnAbstract: Raoultella planticola is an emerging bacterial pathogen responsible for causing infections in both humans and animals. Unfortunately, sporadic reports of carbapenem-resistant R. planticola (CRRP) have been documented worldwide. Here we first reported the complete genome sequence of a CRRP isolate RP_3045 co-carrying blaIMP-4 and blaSHV-12, recovered from a patient in China, and its genetic relatedness to 82 R. planticola strains deposited in the NCBI GenBank database, sourced from humans, animals, and the environment. Whole-genome sequencing was performed using the Illumina NovaSeq 6000 and Oxford Nanopore MinION platforms. Phylogenetic analysis was also performed and visualized using a single nucleotide polymorphism (SNP)-based strategy. The complete genome of R. planticola strain RP_3045 was determined to be 6,312,961 bp in length, comprising five contigs that included one chromosome and four plasmids. RP_3045 was found to be multidrug-resistant and harbored several antimicrobial resistance genes, including both blaIMP-4 and blaSHV-12 genes located on a single plasmid. The most closely related strain was hkcpe63, recovered from humans in Hong Kong, China, in 2014, with 506 SNP differences. R. planticola strains were distributed globally and exhibited strong associations among isolates obtained from different sectors. This study provides evidence for the potential of R. planticola to disseminate carbapenem resistance across different sectors, highlighting the critical need for active and continuous surveillance of CRRP.Keywords: Raoultella planticola, blaIMP-4, blaSHV-12, antimicrobial resistance

Yang Liu,1– 6,&ast; Xiangxin Lan,1– 6,&ast; Juanjuan Lu,1– 6,&ast; Qian Zhang,1– 6 Tingting Zhou,1– 6 Tianxiang Ni,1– 6 Junhao Yan1– 6 1Center for Reproductive Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 3Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, 250012, People’s Republic of China; 4Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, 250012, People’s Republic of China; 5Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, 250012, People’s Republic of China; 6National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, 250012, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianxiang Ni; Junhao Yan, Center for Reproductive Medicine, Shandong University, Jinan, People’s Republic of China, Tel +0531-85651172, Email tianxiangni907@163.com; yyy306@126.comObjective: We evaluate whether next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidy (PGT-A) improves the cumulative pregnancy outcomes of patients with unexplained recurrent implantation failure (uRIF) as compared to conventional in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI).Patients and Methods: This was a retrospective cohort study (2015– 2022). A total of 705 couples diagnosed with uRIF were included in the study. 229 women transferred blastocysts based on morphological grading (IVF/ICSI) and 476 couples opted for PGT-A to screen blastocysts by NGS. Women were further stratified according to age at retrieval (< 38 years and ≥ 38 years). The primary outcome was the cumulative live-birth rate after all the embryos were transferred in a single oocyte retrieval or until achieving a live birth. Confounders were adjusted using binary logistic regression models.Results: Cumulative live-birth rate was similar between the IVF/ICSI group and the PGT-A group after stratified by age: IVF/ICSI vs PGT-A in the < 38 years subgroup (49.7% vs 57.7%, adjusted OR (95% CI) = 1.25 (0.84– 1.84), P = 0.270) and in the ≥ 38 years subgroup (14.0% vs 19.5%, adjusted OR (95% CI) = 1.09 (0.41– 2.92), P = 0.866), respectively. Nonetheless, the PGT group had a lower first-time biochemical pregnancy loss rate (17.0% vs 8.7%, P = 0.034) and a higher cumulative good birth outcome rate (35.2% vs 46.4%, P = 0.014) than the IVF/ICSI group in the < 38 years subgroup. Other pregnancy outcomes after the initial embryo transfer and multiple transfers following a single oocyte retrieval were all similar between groups.Conclusion: Our results showed no evidence of favorable effects of PGT-A treatment on improving the cumulative live birth rate in uRIF couples regardless of maternal age. Use of PGT-A in the < 38 years uRIF patients would help to decrease the first-time biochemical pregnancy loss and increase the cumulative good birth outcome.Keywords: preimplantation genetic testing for aneuploidy, unexplained recurrent implantation failure, cumulative live-birth rate, cumulative good birth outcome

Enyi Zhu,1,2,&ast; Ming Zhong,3,&ast; Tiantian Liang,4,&ast; Yu Liu,3,&ast; Keping Wu,1,2 Zhijuan Zhang,1,2 Shuping Zhao,1,2 Hui Guan,5 Jiasi Chen,6 Li-Zhen Zhang,7 Yimin Zhang1,2 1The Division of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, 510000, People’s Republic of China; 2Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, 510000, People’s Republic of China; 3Department of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, 517108, People’s Republic of China; 4Nephrology Division, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, People’s Republic of China; 5Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, People’s Republic of China; 6Department of Nephrology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510030, People’s Republic of China; 7Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yimin Zhang, The Division of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, People’s Republic of China, Email zhangyim@mail.sysu.edu.cn Li-Zhen Zhang, Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China, Email zhanglzh3@mail2.sysu.edu.cnObjective: Diabetic nephropathy (DN) represents the principal cause of end-stage renal diseases worldwide, lacking effective therapies. Fatty acid (FA) serves as the primary energy source in the kidney and its dysregulation is frequently observed in DN. Nevertheless, the roles of FA metabolism in the occurrence and progression of DN have not been fully elucidated.Methods: Three DN datasets (GSE96804/GSE30528/GSE104948) were obtained and combined. Differentially expressed FA metabolism-related genes were identified and subjected to DN classification using “ConsensusClusterPlus”. DN subtypes-associated modules were discovered by “WGCNA”, and module genes underwent functional enrichment analysis. The immune landscapes and potential drugs were analyzed using “CIBERSORT” and “CMAP”, respectively. Candidate diagnostic biomarkers of DN were screened using machine learning algorithms. A prediction model was constructed, and the performance was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The online tool “Nephroseq v5” was conducted to reveal the clinical significance of the candidate diagnostic biomarkers in patients with DN. A DN mouse model was established to verify the biomarkers’ expression.Results: According to 39 dysregulated FA metabolism-related genes, DN samples were divided into two molecular subtypes. Patients in Cluster B exhibited worse outcomes with a different immune landscape compared with those in Cluster A. Ten potential small-molecular drugs were predicted to treat DN in Cluster B. The diagnostic model based on PRKAR2B/ANXA1 was created with ideal predictive values in early and advanced stages of DN. The correlation analysis revealed significant association between PRKAR2B/ANXA1 and clinical characteristics. The DN mouse model validated the expression patterns of PRKAR2B/ANXA1.Conclusion: Our study provides new insights into the role of FA metabolism in the classification, immunological pathogenesis, early diagnosis, and precise therapy of DN.Keywords: diabetic nephropathy, fatty acid metabolism, molecular subtypes, immune landscape, pharmacotherapy, diagnostic model

Ru Li,1,2,&ast; Baofeng Wu,1,2,&ast; Minmin Han,1,2 Mengnan Li,1,2 Xifeng Yang,1,2 Jian Zhang,1,2 Yi Zhang,3 Yunfeng Liu1 1Department of Endocrinology, The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2The First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunfeng Liu, Department of Endocrinology, The First Hospital of Shanxi Medical University, 85 Jiefang South Road, Taiyuan, People’s Republic of China, Tel +86 18703416196, Email nectarliu@163.com Yi Zhang, Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China, Email yizhang313@163.comAbstract: Uric acid (UA) is the end product of purine metabolism in the human, and the imbalance between production and excretion results in the disturbance of serum uric acid (SUA). There is evidence suggesting that pituitary-target gland hormones can affect UA metabolism through regulating the activity of xanthine oxidase and UA transporters. Related endocrine diseases including thyroid dysfunction, polycystic ovary syndrome, acromegaly and Cushing’s syndrome are often accompanied by elevated UA levels. In addition to the direct influence of abnormal hormones, obesity and insulin resistant play a pivotal role. Diabetes insipidus and the syndrome of inappropriate antidiuretic hormone secretion also present with abnormal SUA levels due to the action of antidiuretic hormone. However, certain evidence within the population is disputed. This review summarized the effects of pituitary-target gland hormones on UA metabolism, and preliminarily described the related mechanisms, offering a theoretical foundation for assessing SUA in endocrine disorders as well as guiding its management.Keywords: uric acid, hyperuricemia, pituitary-target gland, endocrine disease, insulin resistant

Yang Liu,&ast; Xiaoli Wu,&ast; Siting Chen, Wenxia Meng Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenxia Meng, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, 510280, People’s Republic of China, Email mengwx2008@foxmail.comAbstract: Acanthosis nigricans (AN) is a dermatological condition characterised by the symmetrical development of velvety, hyperpigmented plaques predominantly in intertriginous areas such as the axillae, neck, inframammary regions, and groin. The malignant variant of AN is frequently associated with internal malignancies, particularly gastric adenocarcinoma, accounting for 55– 61% of cases. Patients exhibiting characteristic skin lesions are commonly initially evaluated in dermatology departments. This case report details a rare instance of a patient diagnosed with malignant acanthosis nigricans, presenting with only a mild form of florid oral papillomatosis concomitant with ovarian carcinoma. The early identification and management of these subtle clinical manifestations enabled timely intervention for the tumor, resulting in patient survival. There are few reported cases of malignant acanthosis nigricans associated with ovarian cancer. Oral medicine specialists should be cognisant of conditions manifesting as extensive oral papillary hyperplasia, and the possibility of an underlying malignant disease should be considered, particularly in cases of elderly-onset AN presenting exclusively with oral lesions.Keywords: malignant acanthosis nigricans, ovarian cancer, papillary hyperplasia

Xiaoqi Wang,1,2 Yuanjie Hao,3 Yujie Yin,4,5 Yunlong Hou,2,4,5 Ningxin Han,3 Yi Liu,3 Zhen Li,3 Yaru Wei,1 Kun Ma,1 Jiaojiao Gu,1 Yan Ma,1 Hui Qi,4,5 Zhenhua Jia1,4– 6 1Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050090, People’s Republic of China; 2Hebei Yiling Pharmaceutical Research Institute, Shijiazhuang, 050035, People’s Republic of China; 3Graduate School, Hebei Medical University, Shijiazhuang, Hebei, 050017, People’s Republic of China; 4Hebei Academy of Integrated Traditional Chinese and Western Medicine, Shijiazhuang, Hebei, 050035, People’s Republic of China; 5National Key Laboratory for Innovation and Transformation of Luobing Theory, Shijiazhuang, 050035, People’s Republic of China; 6Department of Respiratory, Affiliated Yiling Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050091, People’s Republic of ChinaCorrespondence: Zhenhua Jia, Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050090, People’s Republic of China, Email jzhjiazhenhua@163.com Hui Qi, Hebei Academy of Integrated Traditional Chinese and Western Medicine, Shijiazhuang, Hebei, 050035, People’s Republic of China, Email qihui_qh@163.comPurpose: Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) is a sudden worsening of symptoms in patients with Chronic Obstructive Pulmonary Disease (COPD), such as cough, increased sputum volume, and sputum purulence. COPD and AECOPD are characterized by damage to cilia and increased mucus secretion. Mucociliary clearance (MCC) functions as part of the primary innate system of the lung to remove harmful particles and pathogens together with airway mucus and is therefore crucial for patients with COPD.Methods: AECOPD was induced by cigarette smoke exposure (80 cigarettes/day, 5 days/week for 12 weeks) and lipopolysaccharide (LPS) instillation (200 μg, on days 1, 14, and 84). Rats administered Lianhua Qingke (LHQK) (0.367, 0.732, and 1.465 g/kg/d) or Eucalyptol, Limonene, and Pinene Enteric Soft Capsules (ELP, 0.3 g/kg/d) intragastrically. Pulmonary pathology, Muc5ac+ goblet cell and β-tubulin IV+ ciliated cells, and mRNA levels of forkhead box J1 (Foxj1) and multiciliate differentiation and DNA synthesis associated cell cycle protein (MCIDAS) were assessed by hematoxylin and eosin staining, immunofluorescence staining, and RT-qPCR, respectively. Ciliary morphology and ultrastructure were examined through scanning electron microscopy and transmission electron microscopy. Ciliary beat frequency (CBF) was recorded using a high-speed camera.Results: Compared to the model group, LHQK treatment groups showed a reduction in inflammatory cell infiltration, significantly reduced goblet cell and increased ciliated cell proportion. LHQK significantly upregulated mRNA levels of MCIDAS and Foxj1, indicating promoted ciliated cell differentiation. LHQK protected ciliary structure and maintained ciliary function via increasing the ciliary length and density, reducing ciliary ultrastructure damage, and ameliorating random ciliary oscillations, consequently enhancing CBF.Conclusion: LHQK enhances the MCC capability of ciliated cells in rat with AECOPD by preserving the structural integrity and beating function of cilia, indicating its therapeutic potential on promoting sputum expulsion in patients with AECOPD.Keywords: goblet hyperplasia, ciliary density, ciliary length, ciliary ultrastructure, ciliary beat frequency, CBF

Chenqi Chang,1 Heng Liu,2 Xiaotong Li,2 Dandan Song,1 Yue Liu,1 Chang Lu,1 Yu Zhen,1 Ying Chen,1 Jinguo Xu,1 Weidong Li,1 Xiaobin Jia,3 Zhipeng Chen,1 Rui Chen1 1School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China; 2Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, College of Pharmacy, Dali University, Dali, 671003, People’s Republic of China; 3School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, People’s Republic of ChinaCorrespondence: Rui Chen; Zhipeng Chen, Email chenrui@njucm.edu.cn; czpcpu2000@hotmail.comIntroduction: Enhancing the efficacy of berberine (BBR) in the treatment of ulcerative colitis (UC) through the development of dopamine-coated berberine nanoparticles (PDA@BBR NPs) with ROS-responsive and adhesive properties.Methods: Berberine nanoparticles (BBR NPs) were synthesized using the nonsolvent precipitation method, and their surfaces were coated with polydopamine (PDA) through oxidative polymerization. The PDA@BBR NPs were characterized by transmission electron microscopy (TEM), size analysis, and zeta potential analysis. Drug loading and encapsulation efficiency were analyzed using fluorescence spectroscopy. The responsiveness of these nanoparticles to reactive oxygen species (ROS) was assessed in vitro, while their adhesive properties and therapeutic efficacy on UC were evaluated in vivo.Results: Physicochemical property studies showed that PDA coated BBR NPs nanoparticles have good dispersion and stability. In vitro results showed that PDA@BBR NPs could prolong the retention time of the drug at the colonic site and could realize the gradual drug release under ROS environment. In addition, animal studies showed that PDA@BBR NPs exhibited significant anti-inflammatory effects on DSS-induced colitis and effectively reduced intestinal mucosal damage.Conclusion: PDA@BBR NPs are ROS-responsive nanoparticles that adhere well and have a high drug loading capacity. They have shown therapeutic effects in mice with UC, indicating that this formulation may be a promising treatment option. Keywords: berberine, polydopamine, ROS-responsive, adhesion retention, ulcerative colitis

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

Xin Fang,1 Yalong Yin,2 Haimei Lun,3 Yaoli Liu,1 Shangyong Zhu1 1Department of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Traditional Chinese Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Department of Ultrasound, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Shangyong Zhu, Department of Medical Ultrasound, First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Email zhushangyong2022@sina.cnPurpose: Few studies have assessed the effects of sphingosine kinase 1/sphingosine-1-phosphate (SPHK1/S1P) on microangiogenesis at rat myofascial trigger points (MTrPs) using contrast-enhanced ultrasonography (CEUS). This study aimed to address these deficiencies. Here, we investigated the effects of SPHK1/S1P on MTrP microangiogenesis and the value of CEUS in evaluating these effects.Methods: Forty Sprague‒Dawley rats were subdivided into two groups: control and MTrP groups. MTrPs were established by 8 weeks of the strike procedure combined with eccentric motion and 4 weeks of recovery. All rats were euthanized after having undergone CEUS with an overdose of pentobarbital sodium. MTrP and control tissue samples were removed for haematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) imaging. The tissue was dehydrated, cleared, and embedded before sectioning. The sections were then incubated overnight at 4°C, and immunohistochemistry was carried out with primary antibodies including rabbit anti-CD31, rabbit anti-SPHK1and rabbit anti-S1PR1.Results: MTrP rats exhibited spontaneous electrical activity (SEA) and a local twitch response (LTR) during electromyography (EMG) examination. The CEUS time-intensity curves (TICs) showed that the perfusion intensity in the MTrPs and surrounding tissue area was increased, with faster perfusion than in normal sites, while the TICs in the control group slowly increased and then slowly decreased. The correlation coefficient between the microvessel density (MVD) and sphingosine 1-phosphate receptor 1 (S1PR1) was 0.716 (p < 0.01). Spearman correlation analysis revealed that Spearman’s rho (ρ) values between the MVD and peak intensity (PI), between the MVD and area under the curve (AUC), and between the MVD and SPHK1 were > 0.5 (p < 0.05), > 0.7 (p < 0.01), and > 0.7 (p < 0.01), respectively.Conclusion: CEUS is valuable for detecting microangiogenesis within MTrPs, and SPHK1/S1P plays an important role in promoting MTrP tissue microangiogenesis.Keywords: ultrasound, myofascial pain syndrome, diagnosis, angiogenesis

Haijun Wei,&ast; Ke Wang,&ast; Wei Huang, Yang Liu Department of Vascular Surgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Liu, Department of Vascular Surgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China, Email zjobliu@163.comAbstract: Pyoderma gangrenosum (PG) is a rare autoinflammatory neutrophilic dermatosis clinically characterized by painful nodules, red papules or plaques that rapidly erode into ulcers. We report a 53-year-old febrile male patient with acute peripheral arterial disease who underwent transtibial amputation after failed thrombolysis. Five days after amputation, an ulcer developed around the cannulation site of the right internal jugular vein that was indicative of pathergy. The patient’s fever did not improve after surgery, and purpuric discoloration and punctate ulcers of the skin near the amputation site became apparent, leading to re-debridement. Finally, consultation with a dermatologist raised the possibility of postoperative PG, and additional laboratory tests revealed positive anticardiolipin autoantibodies consistent with antiphospholipid syndrome. The patient was treated with intravenous glucocorticosteroids and antibiotics, and the amputation wound and cannulation site ulcer were found to have healed at the 2-month follow-up. The current report raises the need for vascular surgeons to be aware of this uncommon etiology of arterial thrombosis, and the postoperative appearance of dermatosis and pathergy should alert for PG.Keywords: antiphospholipid syndrome, case report, peripheral artery disease, pyoderma gangrenosum

Zhongxu Jing,&ast; Wenqing Li,&ast; Wei Liao, Ying Lv, Yuwei Liu, Haibo Jiang, Yufei Feng Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin, 150040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yufei Feng, Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Harbin, 150040, People’s Republic of China, Tel +86-18503653988, Email fuf-002@163.comPurpose: The aim of the present study was to fabricate a Fructus Xanthii and Magnolia liliiflora volatile oils liposomes-loaded thermosensitive in situ gel (gel/LIP/volatile oil) for effectively treating allergic rhinitis via intranasal administration.Patients and Methods: Particle size, polymer dispersity index (PDI), entrapment effectiveness, and cumulative drug permeation of the developed liposomes were assessed. Then, a thermoreversible in situ gel was created using the liposomes loaded with volatile oils of Fructus Xanthii and Magnolia liliiflora. The effectiveness of this treatment for allergic rhinitis was confirmed by evaluating nasal symptoms, and hematological results, after injecting the formulation into the ovalbumin (OVA)-sensitized mice, we conducted hematoxylin-eosin staining (HE) and immunohistochemistry to evaluate the outcomes. The effects of the gel/LIP/volatile oil formulation for nasal delivery of volatile oil in the treatment of rhinitis were then assessed.Results: The average particle size was 95.1 ± 3.6 nm, and the encapsulation efficiencies of Fructus Xanthii and Magnolia liliiflora volatile oils were 70.42 ± 5.41% and 67.10 ± 6.08%, respectively. Drug loadings of Fructus Xanthii and Magnolia liliiflora volatile oils were 9.10 ± 0.98% and 16.10 ± 1.03%, respectively. The binary formulation produced a gel rapidly in the nasal cavity with a strong mucosal adherence at a temperature of delivering volatile oil to the nasal mucosa steadily and continuously. After nasal administration, the gel/LIP/volatile oil sustained the volatile oil delivery into the mucosa. In comparison to the monolithic formulations, the gel/LIP/volatile oil binary formulation exhibited superior performance in terms of drug delivery capability and pharmacodynamic effects.Conclusion: This binary preparation displayed the ability to deliver drugs to the nasal mucosa and exhibited positive pharmacodynamic effects in treating OVA-induced rhinitis in mice. As a result, it has the potential to serve as a delivery platform for Traditional Chinese medicine in the treatment of allergic rhinitis.Keywords: volatile oil of Magnolia liliiflora, volatile oil of Fructus Xanthii, liposomes, thermosensitive gel, allergic rhinitis

Gengyao Hu,1,&ast; Yuanhang Pan,1,&ast; Na Yuan,1,&ast; Zhixian Yang,2 Xiuyu Shi,3 Sha Ma,4 Shan Li,4 Xiaohua Hou,5 Fei Liu,5 Dongmei Li,6 Junxiang Bao,7 Yonghong Liu1 1Department of Neurology, Xijing Hospital, Fourth Military Medical University (Air Force Medical University), Xi’an, People’s Republic of China; 2Department of Pediatrics, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Pediatrics, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China; 4Department of Neurology, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China; 5Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 6Department of Dentistry for Special Services, Fourth Military Medical University (Air Force Medical University), Xi’an, People’s Republic of China; 7Department of Aerospace Hygiene, Fourth Military Medical University (Air Force Medical University), Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghong Liu, Email liuyhong@fmmu.edu.cnBackground: Sleep-related facial mandibular myoclonus (SRFMM) remains rare in clinical practice. The aim of this study was to provide a comprehensive understanding of the electroclinical manner, therapeutic regimen, and prognosis of SRFMM.Methods: Twenty-three patients who were diagnosed with SRFMM by clinical manifestation, video-electroencephalography (EEG) and electromyography over bilateral masseter and temporalis muscles were enrolled. Clinical and electrophysiological evaluation as well as follow-up information were recorded and analyzed.Results: The cohort involved 4 infants and 19 adults with a mean onset age of 43.5 years for SRFMM, among whom 19 were male. Twenty-one patients complained of tongue injuries and disturbed night-time sleep. SRFMM in 4 patients were ascribed to oral aripiprazole, brainstem ischemia and brain trauma. In 62 SRFMM episodes, 93.5% occurred in NREM sleep and 6.5% in REM sleep, and all events were associated with EEG arousals. In 13 patients with or without clonazepam, the motor events gradually disappeared, and the rest turned to be sporadic.Conclusion: SRFMM is a characteristic parasomnia manifested by tongue biting and accompanying facial mandibular myoclonus, leading to disrupted sleep. Besides adults, infants can also experience SRFMM with spontaneous remission. Most patients respond well to clonazepam, eventually with favorable prognosis.Keywords: sleep-related facial mandibular myoclonus, tongue biting, movement disorder, SRFMM

Xinchao Liu,1,&ast; Hao Xing,2,3,&ast; Jing Lin,1,3,&ast; Jian Sun,4 Yu Wang,3 Yaxu Liu,5 Wei Cao,1,6 Zhengyin Liu,1 Taisheng Li1,6,7 1Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China; 3Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China; 5Department of International Medical Services, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People’s Republic of China; 6State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 7Tsinghua-Peking Center for Life Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Taisheng Li, Email litsh@263.netBackground: Talaromyces marneffei is prevalent in South Asia. Latent Talaromyces marneffei infection of travellers make the diagnosis difficult. There are similarities in clinical manifestations between Talaromyces marneffei infection and lymphoma. Brain abscess is a rare form of Talaromyces marneffei infection.Case Presentation: We reported a very rare case of a 19-year-old man with HIV infection who suffered from a brain mass and lymphadenopathy. His blood culture, bone marrow culture and sputum culture all grew Talaromyces marneffei. One month after treatment with voriconazole, the symptoms improved except brain mass. Surgical incision of the brain mass showed a compact mass, and pathological analysis showed the coexisting Talaromyces marneffei abscess and lymphoma. The patient is currently in a stable condition after receiving antifungal therapy and chemotherapy.Conclusion: Based on a case report of a traveller who suffered from a brain mass of Talaromyces marneffei abscess and lymphoma after a visit to an endemic area, this review summarized the cases where there was confusion between lymphoma and the brain abscess of Talaromyces marneffei. Talaromyces marneffei infection can be found globally due to the increasing number of international travels. Talaromyces marneffei infection and lymphoma had similar characteristics which is easy to misdiagnose in clinic. Infection may also be accompanied by tumors, especially in patients infected with HIV. The manifestations and imaging of brain abscess of Talaromyces marneffei were not characteristic in different patients.Keywords: Talaromyces marneffei, lymphoma, misdiagnose, HIV, travel

Yue Liu, Shi Qi Xie, Xia Yang, Jing Lan Chen, Jian Rong Zhou School of Nursing, Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Jian Rong Zhou; Shi Qi Xie, School of Nursing, Chongqing Medical University, 1 Medical College Road, Yu Zhong District, Chongqing, 400016, People’s Republic of China, Tel +86-135 0830 0955 ; +86-156 0833 2043, Fax +86-23-63555767, Email 202028@cqmu.edu.cn; xie47@cqmu.edu.cnPurpose: The clinical presentation of Obstructive Sleep Apnea (OSA) in children is insidious and harmful. Early identification of children with OSA, particularly those at a higher risk for severe symptoms, is essential for making informed clinical decisions and improving long-term outcomes. Therefore, we developed and validated a risk prediction model for severity in Chinese children with OSA to effectively identify children with moderate-to-severe OSA in a clinical setting.Patients and Methods: From June 2023 to September 2023, we retrospectively analyzed the medical records of 367 Children diagnosed with OSA through portable bedside polysomnography (PSG). Predictor variables were screened using the least absolute shrinkage and selection operator (LASSO) and logistic regression techniques to construct nomogram to predict the severity of OSA. Receiver operating characteristic curve (ROC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC) were used to determine the discrimination, calibration, and clinical usefulness of the nomogram.Results: A total of 367 children with a median age of 84 months were included in this study. Neck circumference, ANB, gender, learning problem, and level of obstruction were identified as independent risk factors for moderate-severe OSA. The consistency indices of the nomogram in the training and validation cohorts were 0.841 and 0.75, respectively. The nomogram demonstrated a strong concordance between the predicted probabilities and the observed probabilities for children diagnosed with moderate-severe OSA. With threshold probabilities ranging from 0.1 to 1.0, the predictive model demonstrated strong predictive efficacy and yielded improved net benefit for clinical decision-making. ROC analysis was employed to classify the children into high and low-risk groups, utilizing the Optimal Cutoff value of 0.39.Conclusion: A predictive model using LASSO regression was developed and validated for children with varying levels of OSA. This model identifies children at risk of developing OSA at an early stage.Keywords: obstructive sleep apnea, children, cephalometric, prediction nomogram, risk prediction model

Pingyang Ke,1,&ast; Jing Liu,1,2,&ast; Chengzhi Chen,3,&ast; Sen Luo,3,&ast; Huiwen Gu,3,&ast; Juan Gu,4 Yan Liu,1 Yuanlin Ma,1 Yuan Meng,1 Liqin Hu,1 Xin Tian,1 Fei Xiao1 1Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, People’s Republic of China; 2Department of Neurology, Chongqing University Three Gorges Hospital, Chongqing, People’s Republic of China; 3Department of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing, People’s Republic of China; 4Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Xiao; Xin Tian, Email feixiao81@126.com; xintian@cqmu.edu.cnBackground: Zinc oxide nanoparticles (ZnO NPs) has been widely used in various fields and has had an important impact on human public health. In addition, it inevitably damages human health, including neurological diseases. Therefore, this study explored the effect of ZnO NPs on epilepsy.Methods: The effect of ZnO NPs on epilepsy was observed by behavioral analysis. TLR4 expression and autophagy related pathways were detected by RNA-seq and Western blot. In addition, the cell types of autophagy were detected by immunofluorescence. Further, the electrophysiological changes of ZnO NPs induced autophagy were detected by whole-cell patch-clamp. Finally, the recovery experiment was carried out by TLR4 inhibitor (TAK-242).Results: We found that ZnO NPs enhanced epilepsy susceptibility and severity. Through RNA-seq analysis and Western blot, it was found that ZnO NPs affected the changes of TLR4 and autophagy related pathways. In addition, we found that ZnO NPs mainly affects autophagy of inhibitory neurons, resulting in excitation/inhibition imbalance. The autophagy and epileptic phenotypes were reversed with TAK-242. In general, ZnO NPs exacerbate epileptic seizures by modulating the TLR4-autophagy axis.Conclusion: ZnO NPs enhanced the susceptibility and severity of epilepsy. Mechanistically, ZnO NPs affected autophagy by changing the expression of TLR4. In particular, the ZnO NPs mainly affected the synaptic function of inhibitory neuron, leading to excitation/inhibition imbalances.Keywords: zinc oxide nanoparticles, epilepsy, excitation/inhibition balance, autophage

Meiju Deng,1,2,&ast; Yongqin Zeng,2,3,&ast; Ying Liu,2 Xiaolei Wang,1,2 Na Chen,1,2 Mengyuan Zhang,1,4– 6 Meiqing Jiang,1,4– 6 Hongxin Zhao,2 Juan Du1,4– 6 1Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 2Clinical Center for HIV/AIDS, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 3Department of Nephrology, The Affiliated Hospital Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China; 4Beijing Institute of Infectious Diseases, Beijing, 100015, People’s Republic of China; 5National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 6National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing, 100015, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Du; Hongxin Zhao, Email duj656@ccmu.edu.cn; Drzhao66@ccmu.edu.cnBackground: The aging of the immune system is associated with various diseases. It is worth exploring the changes of the immune system in aging. Previous studies have shown that aged T cells have enhanced expression of co-inhibitory molecules. However, it remains unclear whether aged NK cells exhibit similar characteristics to aged T cells. The objective of our research was to clarify this aspect.Patients and Methods: This study included 98 adults aged 24– 90 years (50 males and 48 females). We detected the subset of peripheral blood NK cells and the expression of various receptors on NK cells among donors of different age groups by flow cytometry. Immune subsets were initially defined by forward and side-scatter characteristics and then staining with the appropriate marker.Results: The absolute number and subset distribution of NK cells were not associated with age. However, CD57 expression and CD69 expression were correlated with age. Furthermore, we found that PD-1 was up-regulated on NK cells in older people, associated with aging, while no such change was observed in other co-inhibitory molecules, including 2B4, CTLA-4, TIM-3, BTLA, CD70, CD39, CD160, and TIGIT. PD-1+ NK cells expressed high levels of CD57 and CD69, indicating PD-1+ NK cells displayed a phenotype of over-activation and aging.Discussion: This study indicated that PD-1+ NK cells were one of the characteristics of NK cells in older people.Conclusion: This study indicated that PD-1+ NK cells were one of the characteristics of NK cells in older people. Those findings provided new ideas to explore the underlying drivers of NK aging.Keywords: PD-1, NK cell, aging, co-inhibitory molecules

Using an AZ91D magnesium alloy as the research object, a three-dimensional (3D) numerical model was created and simulated using simulation analysis software. The effects of a rotating electromagnetic field (REMF), a pulsed electromagnetic field (PEMF) and a rotating pulsed electromagnetic field (R-PEMF) on the magnetic field and the flow field of a metal melt were investigated. The simulation results show that during the REMF treatment a rotational force is generated on the cross-section of the melt, and the PEMF exerts a magnetic pressure on the cross-section of the melt. Under the combined effect of these two forces, the Lorentz force increases parallel to the melt axis, and a secondary flow directed towards the core of the melt is generated, which contributes to the homogenization of the melt. By analyzing the solidification structure and elemental distribution of the metal, R-PEMF was shown to effectively improve the solidification structure and macrosegregation of Al in AZ91D magnesium alloy.

Yan Ding,1,&ast; Banqin Wang,2,&ast; Yongjun Liu,1 Shengjie Dong,1 Xuri Sun,1 Zhilin Cao,1 Leisheng Wang1 1Department of Orthopedics, Yantaishan Hospital, Yantai, People’s Republic of China; 2Department of Blood Transfusion, Shandong Provincial Qianfoshan Hospital Affiliated with Shandong First Medical University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leisheng Wang, Department of Orthopedics, Yantaishan Hospital, No. 10087 Keji Road, Yantai, 264003, People’s Republic of China, Tel +86-13792566016 ; +86-0535-6863898, Email 37724148@qq.comPurpose: Percutaneous pedicle screw fixation is a common minimally invasive treatment for traumatic thoracolumbar and lumbar fractures; however, research on hardware removal after successful healing is limited. We aimed to introduce a rapid, safe, minimally invasive, and cost-effective method for percutaneous pedicle screw removal.Patients and Methods: We conducted a retrospective analysis of demographic (age, sex, body mass index, alcohol use, and current smoking), clinical (hypertension and diabetes mellitus), surgical (affected levels, number of screws, time of surgery, and blood loss), and treatment cost characteristics of 92 patients who had undergone percutaneous pedicle screw removal between May 2016 and February 2023. The first 57 patients underwent the conventional method, and the remaining 35 underwent the modified method. Independent-sample t-tests and chi-square tests were used to compare continuous and categorical variables, respectively, between the two groups.Results: No significant differences were observed in the demographic parameters, complications, or affected levels between the groups. However, the average surgical time (P=0.000) was significantly shorter, and the average blood loss volume (P=0.002) and total cost (P=0.000) were significantly lower in the modified group than in the conventional group.Conclusion: Compared with the conventional method, our modified method can shorten the surgical time, reduce blood loss, and reduce the total cost of treatment. It is a quick and safe minimally invasive method that does not require additional surgical instruments and is suitable for implementation in primary hospitals.Keywords: bone screw, device, Kirschner wire, surgery, control

Jian Jin, Jie Li, Yonghong Liu, Qingfeng Shi, Bo Zhang, Yanting Ji, Pengfei Hu Thyroid and Breast Surgery Department, Cangzhou Central Hospital, Cangzhou, Hebei, 061000, People’s Republic of ChinaCorrespondence: Jie Li, Thyroid and Breast Surgery Department, Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou, Hebei, 061000, People’s Republic of China, Email lijie@hebmu.edu.cnBackground: Breast cancer and thyroid cancer are two prevalent malignancies in women, and a potential association between the two diseases has been suggested.Methods: This retrospective case-control study was conducted involving 97 patients with breast cancer and thyroid cancer (BC-TC group) and 97 age-matched patients with breast cancer alone (BC group). Thyroid hormone levels, including triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH), were analyzed in healthy controls, BC patients, and BC-TC patients.Results: BC-TC patients exhibited a higher rate of estrogen receptor (ER) and progesterone receptor (PR) positivity compared to BC patients. Serum T3 levels were significantly decreased in BC and BC-TC patients compared to healthy controls. However, there was no significant difference in T3 levels between BC and BC-TC patients. Serum TSH levels were significantly higher in BC-TC patients compared to BC patients.Conclusion: ER positivity, PR positivity, and serum TSH levels greater than 4.45 mU/L were independent risk factors for primary thyroid cancer in breast cancer patients.Keywords: breast cancer, thyroid cancer, estrogen receptor, ER

Yang Liu,1,2,&ast; Hui Yang,1,2,&ast; Xueshu Fu,1,2 Luting Zhong,1,2 Ping Xu,1,2 Fang Fang,1,2 Ying Liu,1,2 Qing Li,1,2 Ya’nan Yan,1,2 Shanchuang Wei,1,2 Junqing Wang,1,2 Chunhua Zhang1– 3 1Department of Gynaecology, Affiliated Hospital of YangZhou University Huai ‘an Maternal and Child Health Care Center, Huai’an, Jiangsu, People’s Republic of China; 2Department of Gynaecology, The Huai’an Maternity and Child Clinical College of Xuzhou Medical University, Huai’an, Jiangsu, People’s Republic of China; 3Department of Integrated Traditional Chinese & Western Clinical Medicine, Macau University of Science and Technology, Macau, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunhua Zhang, Department of Gynaecology, The Huai’an Maternity and Child Clinical College of Xuzhou Medical University, Huai’an, Jiangsu, People’s Republic of China, Tel +86-13952326117, Email hafyzch@126.comBackground: Multiple primary cancer (MPC) refers to the presence of more than one cancer in an individual. Triple primary malignancies are uncommon.Case: We report the case of a 50-year-old postmenopausal woman in our gynecology department, diagnosed with endometrial cancer, ovarian cancer, and unilateral breast cancer. She carried germline mutations in BRCA2, PALB2, and RECQL4, along with a somatic pathogenic variant in TP53. Endometrial cancer patients harboring germline pathogenic variants in BRCA2 exhibit a heightened risk of ovarian and breast cancer. BRCA2 is known to play a role in the development of ovarian and breast cancer, while PALB2 is identified as a gene associated with breast cancer susceptibility. RECQL4 has been linked to breast cancer, cervical cancer, and other tumors.Conclusion: Genetic testing may be imperative for identifying MPC in endometrial cancer patients. For individuals with BRCA2 and other gene pathogenic variants, routine examination and monitoring of the endometrium, ovaries, breasts, and other sites prone to polygenic cancer are recommended.Keywords: multiple primary cancer, endometrial cancer, ovarian cancer, breast cancer, genetic test

Xian Ding,1,&ast; Wenqi Liang,2,&ast; Hongjuan Xia,1,&ast; Yuee Liu,2 Shuxiong Liu,1 Xinyu Xia,1 Xiaoli Zhu,1 Yongyan Pei,3 Dewen Zhang4 1Department of Emergency, Third Affiliated Hospital of Naval Medical University, Shanghai, People’s Republic of China; 2Department of Emergency, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 3School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan, People’s Republic of China; 4Longhua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongyan Pei, School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, No. 9-13, Zhongshan Campus, No. 13, Changmingshui Avenue, Wuguishan, Zhongshan City, Guangdong Province, People’s Republic of China, Email peiyongyan@gdpu.edu.cn Dewen Zhang, Longhua Clinical Medical College, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong New Area, Shanghai, People’s Republic of China, Email zhangdewen120@hotmail.comBackground: Sepsis was a high mortality and great harm systemic inflammatory response syndrome caused by infection. lncRNAs were potential prognostic marker and therapeutic target. Therefore, we expect to screen and analyze lncRNAs with potential prognostic markers in sepsis.Methods: Transcriptome sequencing and limma was used to screen dysregulated RNAs. Key RNAs were screened by correlation analysis, lncRNA-mRNA co-expression and weighted gene co-expression network analysis. Immune infiltration, gene set enrichment analysis and gene set variation analysis were used to analyze the immune correlation. Kaplan–Meier curve, receiver operator characteristic curve, Cox regression analysis and nomogram were used to analyze the correlation between key RNAs and prognosis. Sepsis model was established by lipopolysaccharide-induced HUVECs injury, and then cell viability and migration ability were detected by cell counting kit-8 and wound healing assay. The levels of apoptosis-related proteins and inflammatory cytokines were detected by RT-qPCR and Western blot. Reactive Oxygen Species and superoxide dismutase were detected by commercial kit.Results: Fourteen key differentially expressed lncRNAs and 663 key differentially expressed genes were obtained. And these lncRNAs were closely related to immune cells, especially T cell activation, immune response and inflammation. Subsequently, Subsequently, lncRNA PRKCQ-AS1 was identified as the regulator for further investigation in sepsis. RT-qPCR results showed that PRKCQ-AS1 expression was up-regulated in clinical samples and sepsis model cells, which was an independent prognostic factor in sepsis patients. Immune correlation analysis showed that PRKCQ-AS1 was involved in the immune response and inflammatory process of sepsis. Cell function tests confirmed that PRKCQ-AS1 could inhibit sepsis model cells viability and promote cell apoptosis, inflammatory damage and oxidative stress.Conclusion: We constructed immune-related lncRNA-mRNA regulatory networks in the progression of sepsis and confirmed that PRKCQ-AS1 is an important prognostic factor affecting the progression of sepsis and is involved in immune response.Keywords: sepsis, immune-related lncRNA, lncRNA-mRNA, PRKCQ-AS1, prognosis and progress

Tianhao Cong,1 Chao Yang,1 Qi Cao,2 Jinrui Ren,1 Yingen Luo,1 Pei Yuan,2 Bo Zheng,2 Yu Liu,1 Hongcai Yang,1 Wendi Kang,1 Aixin Ou,1 Xiao Li1 1Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Xiao Li, Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Tel +86-13910309111, Fax +86-028-88092354, Email simonlixiao@gmail.comPurpose: Transarterial chemoembolization (TACE) represents a significant therapeutic modality for hepatocellular carcinoma (HCC). We aimed to develop a gene signature to accurately predict patient TACE response and explore the underlying mechanisms.Methods: Three independent datasets were utilized, including GSE104580, GSE14520 and external validation from the Cancer Hospital Chinese Academy of Medical Sciences. GSE104580 was randomly partitioned into a training set and a validation set, whereas GSE14520 was categorized into a resection group and a TACE group. Logistic regression was used to develop a TACE effectiveness model. Immunohistochemistry is utilized to confirm the protein expression trends of the signature genes. Immune infiltration and functional enrichment analyses were conducted to investigate the potential underlying mechanisms.Results: A 2-gene signature consisting of glycine N-methyltransferase (GNMT) and matrix metalloproteinase-12 (MMP12) was constructed, and based on this, all the patients were assigned TACE effectiveness scores and categorized into high effectiveness (HE) and low effectiveness (LE) groups. The HE group exhibited a better prognosis than the LE group in the various cohorts (p < 0.05). In the external validation set, immunohistochemistry confirmed the expression of the signature genes exhibiting an upregulated trend of GNMT in the HE group and MMP12 in the LE group, the LE group also exhibited a poorer prognosis [for overall survival (OS), HE group: 881 days vs LE group: 273 days (p < 0.05), and for progression-free survival (PFS), HE group: 458 days vs LE group: 136 days (p < 0.05)]. Multivariate analysis in all the datasets identified LE status as an independent risk factor for OS, disease-free survival (DFS) and PFS. The infiltration level of M0 macrophages and activated mast cells in the LE group was significantly higher than in the HE group. The hypoxia signaling pathway and glycolysis pathway were significantly enriched in the LE group.Conclusion: The loss of GNMT and the overexpression of MMP12 may be critical factors influencing TACE efficacy.Keywords: hepatocellular carcinoma, transarterial chemoembolization, immune infiltration, mast cell, glucose metabolism, hypoxic microenvironment

Linyuan Gui,1,&ast; Qingyuan Ye,2,&ast; Lu Yu,3 Geng Dou,1 Yang Zhou,1 Yang Liu,4 Yanqi Zhang,5 Xiaoshan Yang,1,6 Fang Jin,5 Shiyu Liu,1 Yan Jin,1 Lili Ren1 1State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 2State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Digital Dentistry Center, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 3Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, 250012, People’s Republic of China; 4Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 5State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 6Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lili Ren; Yan Jin, State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China, Email lanyangddgy@qq.com; yanjin@fmmu.edu.cnBackground: Osteoporosis is a highly prevalent disease that causes fractures and loss of motor function. Current drugs targeted for osteoporosis often have inevitable side effects. Bone marrow mesenchymal stem cell (BMSCs)-derived apoptotic extracellular vesicles (ApoEVs) are nanoscale extracellular vesicles, which has been shown to promote bone regeneration with low immunogenicity and high biological compatibility. However, natural ApoEVs cannot inherently target bones, and are often eliminated by macrophages in the liver and spleen. Thus, our study aimed to reconstruct ApoEVs to enhance their bone-targeting capabilities and bone-promoting function and to provide a new method for osteoporosis treatment.Methods: We conjugated a bone-targeting peptide, (Asp-Ser-Ser)6 ((DSS)6), onto the surface of ApoEVs using standard carbodiimide chemistry with DSPE-PEG-COOH serving as the linker. The bone-targeting ability of (DSS)6-ApoEVs was determined using an in vivo imaging system and confocal laser scanning microscopy (CLSM). We then loaded ubiquitin ligase RING finger protein146 (RNF146) into BMSCs via adenovirus transduction to obtain functional ApoEVs. The bone-promoting abilities of (DSS)6-ApoEVs and (DSS)6-ApoEVsRNF146 were measured in vitro and in vivo.Results: Our study successfully synthesized bone-targeting and gained functional (DSS)6-ApoEVsRNF146 and found that engineered ApoEVs could promote osteogenesis in vitro and exert significant bone-targeting and osteogenesis-promoting effects to alleviate osteoporosis in a mouse model.Conclusion: To promote the bone-targeting ability of natural ApoEVs, we successfully synthesized engineered ApoEVs, (DSS)6-ApoEVsRNF146 and found that they could significantly promote osteogenesis and alleviate osteoporosis compared with natural ApoEVs, which holds great promise for the treatment of osteoporosis. Keywords: osteoporosis, mesenchymal stem cells, apoptotic extracellular vesicles, bone-targeting, bone regeneration

Chuling Hu,1,&ast; Yan Liu,2,&ast; Wei Cao,3,&ast; Na Li,4 Shen Gao,5 Zhuo Wang,5 Fenfen Gu2 1Department of Pharmacy, Jiaxing Maternity and Child Health Care Hospital, Affiliated Women and Children’s Hospital of Jiaxing University, Jiaxing, People’s Republic of China; 2Department of Clinical Pharmacy, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Neurovascular Disease, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 4Department of Pathology, Jiaxing Maternity and Child Health Care Hospital, Affiliated Women and Children’s Hospital of Jiaxing University, Jiaxing, People’s Republic of China; 5Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuo Wang; Fenfen Gu, Email wangzhou088@163.com; fenfen09@163.comIntroduction: Chemotherapy is still the treatment of choice for advanced triple-negative breast cancer. Chemotherapy combined with immunotherapy is being tried in patients with triple-negative breast cancer. As a kind of “cold tumor”, triple-negative breast cancer has a bottleneck in immunotherapy. Indoleamine 2, 3-dioxygenase-1 inhibitors can reverse the immunosuppressive state and enhance the immune response.Methods: In this study, mesoporous silica nanoparticles were coated with the chemotherapeutic drug doxorubicin and indoleamine 2, 3-dioxygenase 1 inhibitor 1-Methyl-DL-tryptophan (1-MT), and then encapsulate the surfaces of a triple-negative breast cancer cell membrane to construct the tumor dual-targeted delivery system CDIMSN for chemotherapy and immunotherapy, and to investigate the immunogenic death effect of CDIMSN.Results and discussion: The CDIMSN could target the tumor microenvironment. Doxorubicin induced tumor immunogenic death, while 1-MT reversed immunosuppression. In vivo findings showed that the tumor size in the CDIMSN group was 2.66-fold and 1.56-fold smaller than that in DOX and DIMSN groups, respectively. CDIMSN group was better than naked DIMSN in stimulating CD8+T cells, CD4+T cells and promoting Dendritic Cells(DC) maturation. In addition, blood analysis, biochemical analysis and Hematoxylin staining analysis of mice showed that the bionic nanoparticles had good biological safety. Keywords: immunogenic cell death, doxorubicin, bionic nanoparticle, IDO1 inhibitor, triple-negative breast cancer

Ying Lv, Wenqing Li, Wei Liao, Haibo Jiang, Yuwei Liu, Jiansheng Cao, Wenfei Lu, Yufei Feng Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin, 150040, People’s Republic of ChinaCorrespondence: Yufei Feng, 150040, Tel +86-18503653988, Email fuf-002@163.comAbstract: Natural products have proven to have significant curative effects and are increasingly considered as potential candidates for clinical prevention, diagnosis, and treatment. Compared with synthetic drugs, natural products not only have diverse structures but also exhibit a range of biological activities against different disease states and molecular targets, making them attractive for development in the field of medicine. Despite advancements in the use of natural products for clinical purposes, there remain obstacles that hinder their full potential. These challenges include issues such as limited solubility and stability when administered orally, as well as short durations of effectiveness. To address these concerns, nano-drug delivery systems have emerged as a promising solution to overcome the barriers faced in the clinical application of natural products. These systems offer notable advantages, such as a large specific surface area, enhanced targeting capabilities, and the ability to achieve sustained and controlled release. Extensive in vitro and in vivo studies have provided further evidence supporting the efficacy and safety of nanoparticle-based systems in delivering natural products in preclinical disease models. This review describes the limitations of natural product applications and the current status of natural products combined with nanotechnology. The latest advances in nano-drug delivery systems for delivery of natural products are considered from three aspects: connecting targeting warheads, self-assembly, and co-delivery. Finally, the challenges faced in the clinical translation of nano-drugs are discussed. Keywords: natural products, nanotechnology, drug delivery, targeting

Kui Zhang,1,&ast; Yan Liu,2,&ast; Zhenrui Zhao,1 Xuewen Shi,1 Ruihao Zhang,1 Yixiang He,1 Huaibin Zhang,1 Wenji Wang3 1The First Clinical Medical College of Lanzhou University, Lanzhou, People’s Republic of China; 2Department of Gynecology, First Affiliated Hospital of Xi ‘an Medical College, Xi’ an, People’s Republic of China; 3Department of Orthopedics, the First Hospital of Lanzhou University, Lanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenji Wang, The First Hospital of Lanzhou University, Lanzhou, 730000, People’s Republic of China, Tel +8613893221698, Email ldyyjzwwj@outlook.comBackground: Polyvinyl alcohol/Chitosan hydrogel is often employed as a carrier because it is non-toxic, biodegradable, and has a three-dimensional network structure. Meanwhile, Magnesium-doped nano-hydroxyapatite(Mg-nHA) demonstrated high characterization to promote the osteogenic differentiation of bone marrow derived mesenchymal stem cell(BMSCs). Therefore, in order to develop a porous hydrogel scaffold for the application of bone tissue engineering, an appropriate-type Mg-nHA hydrogel scaffold was developed and evaluated.Methods: A composite hydrogel containing magnesium-doped nano-hydroxyapatite (Mg-nHA/PVA/CS) was developed using a magnetic stirring-ion exchange method and cyclic freeze-thaw method design, with polyvinyl alcohol and chitosan as the main components. Fourier transform infrared spectra (FTIR), electron energy dispersive spectroscopy (EDS), X-ray photoelectron spectrometer (XPS) and scanning electron microscopy (SEM) were employed to analyze the chemical structure, porosity, and elemental composition of each hydrogels. The equilibrium swelling degree, moisture content, pH change, potential for biomineralization, biocompatibility, the osteogenic potential and magnesium ion release rate of the composite hydrogel were also evaluated.Results: SEM analysis revealed a well-defined 3D spatial structure of micropores in the synthesised hydrogel. FTIR analysis showed that doping nanoparticles had little effect on the hydrogel’s structure and both the 5% Mg-nHA/PVA/CS and 10% Mg-nHA/PVA/CS groups promoted amide bond formation. EDS observation indicated that the new material exhibited favourable biomineralization ability, with optimal performance seen in the 5% Mg-nHA/PVA/CS group. The composite hydrogel not only displayed favourable water content, enhanced biocompatibility, and porosity (similar to human cancellous bone), but also maintained an equilibrium swelling degree and released magnesium ions that created an alkaline environment around it. Additionally, it facilitated the proliferation of bone marrow mesenchymal stem cells and their osteogenic differentiation.Conclusion: The Mg-nHA/PVA/CS hydrogel demonstrates significant potential for application in the field of bone repair, making it an excellent composite material for bone tissue engineering. Keywords: magnesium-doped nano-hydroxyapatite, polyvinyl alcohol, chitosan, hydrogel, physical crosslinking

Tong Chen,1– 3 Shiquan Wu,1 Ling Feng,4 SiYu Long,1 Yu Liu,1,2 WenQian Lu,5 Wenya Chen,1 Guoai Hong,1 Li Zhou,1 Fang Wang,1 Yuechan Luo,1 Hequn Zou1,3,5 1Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, People’s Republic of China; 2Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National Regional Key Technology Engineering Laboratory for Medical Ultrasound School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, People’s Republic of China; 3Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 4Department of Nephrology, Shenzhen Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 5Department of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of ChinaCorrespondence: Hequn Zou, School of Medicine, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China, Email zouhequn@cuhk.edu.cnBackground: The annual prevalence of metabolic syndrome (MetS) is increasing. Therefore, early screening and recognition of MetS are critical. This study aimed to evaluate the association between high-density lipoprotein (HDL) subclasses and MetS and to examine whether they could serve as early indicators in a Chinese community-based population with normal high-density lipoprotein cholesterol (HDL-C) levels.Methods: We used microfluidic chip technology to measure HDL subclasses in 463 people with normal HDL levels in 2018. We assessed how HDL subclasses correlated with and predicted insulin resistance (IR) and metabolic syndrome (MetS), evaluated by homeostatic model insulin resistance index (HOMA-IR) and the 2009 International Diabetes Federation (IDF), the American Heart Association (AHA), and the National Heart, Lung, and Blood Institute (NHLBI) criteria, respectively. We used correlation tests and ROC curves for the analysis.Results: The results indicate that there was a negative association between HDL2b% and the risk of IR and MetS in both sexes. Subjects in the highest quartile of HDL2b% had a significantly lower prevalence of IR and MetS than those in the lowest quartile (P< 0.01). Correlation analysis between HDL2b% and metabolic risk factors showed that HDL2b% had a stronger association with these factors than HDL-C did in both sexes. ROC curve analysis also showed that HDL2b% had significant diagnostic value for IR and MetS compared to other lipid indicators.Conclusion: This study showed that MetS alters the distribution of HDL subclasses even when HDL-C levels are within the normal range. HDL-2b% has better diagnostic value for IR and MetS than HDL-C alone and may be a useful marker for early screening.Keywords: HDL subclass, insulin resistance, metabolic syndrome, normal HDL-C population

Zhengjia Zhang,1,&ast; Xinyi Luo,1,&ast; Xiaoxia Xue,1 Mingshi Pang,1 Xiangpeng Wang,1 Liuchunyang Yu,1 Jinxiu Qian,1 Xiaoyu Li,1 Meng Tian,1 Aiping Lu,2 Cheng Lu,3 Yuanyan Liu1 1School of Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hongkong, People’s Republic of China; 3Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanyan Liu; Cheng Lu, Email yyliu_1980@163.com; lv_cheng0816@163.comBackground: The morbidity and mortality of triple-negative breast cancer (TNBC) are still high, causing a heavy medical burden. CCL5, as a chemokine, can be involved in altering the composition of the tumor microenvironment (TME) as well as the immunosuppressive degree, and has become a very promising target for the treatment of TNBC. Dysregulation of microRNAs (miRNAs) in tumor tissues is closely related to tumor progression, and its utilization can be used to achieve therapeutic purposes. Engineered exosomes can avoid the shortcomings of miRNAs and also enhance their targeting and anti-tumor effects through engineering. Therefore, we aimed to create a cRGD-modified exosome for targeted delivery of miR-588 and to investigate its effect in remodeling immunosuppressive TME by anchoring CCL5 in TNBC.Methods: In this study, we loaded miR-588 into exosomes using electroporation and modified it with cRGD using post insertion to obtain cRGD-Exos/miR-588. Transmission electron microscopy (TEM), nanoparticle tracking assay technique (NTA), Western Blots, qPCR, and flow cytometry were applied for its characterization. CCK-8, qPCR and enzyme-linked immunosorbent assay (ELISA), in vivo fluorescence imaging system, immunohistochemistry and H&E staining were used to explore the efficacy as well as the mechanism at the cellular level as well as in subcutaneous graft-tumor nude mouse model.Results: The cRGD-Exos/miR-588 was successfully constructed and had strong TNBC tumor targeting in vitro and in vivo. Meanwhile, it has significant efficacy on TME components affected by CCL5 and the degree of immunosuppression, which can effectively control TNBC with good safety.Conclusion: In this experiment, cRGD-Exos/miR-588 was prepared to remodel immunosuppressive TME by anchoring CCL5, which is affected by the vicious cycle of immune escape. Overall, cRGD-Exos/miR-588 explored the feasibility of targeting TME for the TNBC treatment, and provided a competitive delivery system for the engineered exosomes to deliver miRNAs for antitumor therapy drug.Keywords: engineered exosome, triple negative breast cancer, miR-588, CCL5, tumor environment

Wenyi Du,1,&ast; Yixuan Wang,2,&ast; Chen Song,1 Zhiqiang Tian,1 Yuan Liu,1 Wei Shen1 1Department of General Surgery, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of China; 2Medical Integration and Practice Center, Reproductive Hospital Affiliated to Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuan Liu; Wei Shen, Department of General Surgery, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of China, Tel +86 17852061572 ; +86 13385110723, Email liuyuanjs@outlook.com; shenweijs@outlook.comPurpose: Previous studies have shown a correlation between diabetes mellitus and gallstone formation. The atherogenic index of plasma (AIP) is associated with many metabolic diseases. However, insufficient evidence still exists to elucidate the association between AIP and gallstones. The primary objective of this study was to investigate the correlation between AIP and gallstones in US adults, and the secondary objective was to analyze whether diabetes plays a mediating role in the association.Patients and Methods: Using data from the National Health and Nutrition Survey (NHANES) conducted between 2017 and March 2020, this study investigated the association between AIP and gallstone incidence in US adults. A variety of statistical methods were used to analyze the data in this study, including multivariate logistic regression, subgroup analyses, restricted cubic spline curves (RCS), and mediation effects analysis. In addition, two-stage linear regression was used to detect possible threshold and saturation effects.Results: A total of 6952 subjects were enrolled in the trial, of which 748 patients were diagnosed with gallstones. A significant positive association between AIP and gallstones was observed by fully adjusted multivariate logistic regression analysis, with an odds ratio (OR) of 1.45 and a 95% confidence interval (CI) of (1.09, 1.93). In addition, a non-linear positive association and saturation effect between AIP and gallstones were found, with an inflection point of 0.2246. Mediation analysis showed that diabetes had a mediating effect of 16.9% in the association between AIP and gallstones.Conclusion: This study suggests that elevated levels of AIP are linked to an augmented vulnerability to gallstone development, with diabetes serving as a mediating factor. These findings present a novel perspective on clinical approaches to prevent and manage gallstones.Keywords: gallstones, atherogenic index of plasma, diabetes mellitus, National Health and Nutrition Examination Survey, cross-sectional studies

Yuguo Liu,1 Bo Zhang,1 Haichen Lv,1 Yifan Zhu,2 Xuchen Zhou,1 Hao Zhu,1 Lei Guo1 1Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Lei Guo; Hao Zhu, Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian City, 116011, People’s Republic of China, Tel +86 411-83635963 ; +86 411-83635963, Email leiguo@dmu.edu.cn; drhaozhudmu@163.comObjective: To investigate the precise changes in the lumen and lesions, and clinical outcomes after DCB treatment for de-novo coronary lesions exceeding 2.5 mm in diameter through a detailed analysis of OCT.Methods: This is a prospective study including 53 consecutive patients with 55 de-novo coronary lesions, who underwent DCB angioplasty-only between January 2021 and April 2022. Quantitative coronary angiography (QCA) and OCT were performed before percutaneous coronary interventions (PCI), immediately after PCI, and at 6– 9 months follow-up after PCI. Target lesion failure (TLF) was the primary endpoint of the present study. Multivariate logistic regression analysis was performed to identify the predictors or risks for late lumen enlargement (LLE).Results: A total of 52 patients were successfully treated with DCB. The median follow-up was 7 months, and the incidence of TLF was 7.5%. After the DCB procedure, 43 patients had their scheduled angiographic and OCT examination. QCA demonstrated that the late lumen loss was − 0.79 ± 0.28 mm. OCT demonstrated LLE in 79.1% and dissection healing in 65.1% of lesions. After multivariable logistic analysis, type B dissection (odds ratio [OR] 2.92, 95% confidence interval [CI] 1.34– 7.41, p = 0.037) was found to be a predictor of LLE, but lipid plaque (OR 0.09, 95% CI 0.01– 0.63, p = 0.015) was a risk of LLE.Conclusion: This is the first and largest prospective study to assess the outcomes of DCB treatment for de-novo coronary lesions exceeding 2.5 mm in diameter and the detection of significant vessel enlargement and dissection healing guide by OCT. DCB could be a novel, safe and effective treatment for de-novo coronary lesions exceeding 2.5 mm in diameter through a detailed analysis of OCT.Keywords: drug-coated balloon, optical coherence tomography, late lumen enlargement, de novo, coronary artery disease