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Fei Shu,* Hong Chen,* Zhihao Zhang, Zhiyue Dun, Weijin Lv, Wangxinyue Sun, Mei Liu Department of Prosthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mei Liu, Department of Prosthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, People’s Republic of China, Tel +86-25-69593081, Fax +86-25-69593186, Email liumei2017@njmu.edu.cnIntroduction: Poor interfacial bonding between the fibers and resin matrix in fiber-reinforced composites (FRCs) is a significant drawback of the composites. To enhance the mechanical properties of FRC, fibers were modified by depositing SiO2 nanofilms via the atomic layer deposition (ALD) technique. This study aims to evaluate the effect of ALD treatment of the fibers on the mechanical properties of the FRCs.Methods: The quartz fibers were modified by depositing different cycles (50, 100, 200, and 400) of SiO2 nanofilms via the ALD technique and FRCs were proposed from the modified fibers. The morphologies, surface characterizations of nanofilms, mechanical properties, and cytocompatibility of FRCs were systematically investigated. Moreover, the shear bond strength (SBS) of FRCs to human enamel was also evaluated.Results: The SEM and SE results showed that the ALD-deposited SiO2 nanofilms have good conformality and homogeneity. According to the results of FTIR and TGA, SiO2 nanofilms and quartz fiber surfaces had good chemical combinations. Three-point bending tests with FRCs showed that the deposited SiO2 nanofilms effectively improved FRCs’ strength and Group D underwent 100 deposition cycles and had the highest flexural strength before and after aging. Furthermore, the strength of the FRCs demonstrated a crescendo-decrescendo tendency with SiO2 nanofilm thickness increasing. The SBS results also showed that Group D had outstanding performance. Moreover, the results of cytotoxicity experiments such as cck8, LDH and Elisa, etc., showed that the FRCs have good cytocompatibility.Conclusion: Changing the number of ALD reaction cycles affects the mechanical properties of FRCs, which may be related to the stress relaxation and fracture between SiO2 nanofilm layers and the built-up internal stresses in the nanofilms. Eventually, the SiO2 nanofilms could enhance the FRCs’ mechanical properties and performance to enamel by improving the interfacial bonding strength, and have good cytocompatibility. Keywords: atomic layer deposition, SiO2 nanofilms, surface modification, interfacial bonding

Weihao Lv,1,&ast; Zhe Ruan,2,&ast; Qianqian Zhang,3,&ast; Yaxuan Wei,4,&ast; Xiuquan Wu,1 Ya-Nan Dou,1 Wangshu Chao,1 Xiaowei Fei,1 Zhou Fei1 1Department of Neurosurgery, Xijing Hospital, Air Force Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 2Department of Neurology, Tangdu Hospital, Air Force Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 3Department of Respiratory Medicine, Lanzhou University Second Hospital, Lanzhou, 730070, People’s Republic of China; 4Department of Neurology, Gansu Province Central Hospital, Lanzhou, 730070, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaowei Fei; Zhou Fei, Xijing Hospital, Air Force Medical University, No. 127, Changle West Road, Xincheng District, Shaanxi, 710032, People’s Republic of China, Tel +86-1882928538, Email xiaowei_fei@fmmu.edu.cn; feizhou@fmmu.edu.cnPurpose: We aim to explore the relationship between Homer1 and the outcomes of AIS patients at 3 months.Patients and Methods: This prospective cohort study was conducted from May 2022 to March 2023. In this study, we investigated the association between serum Homer1 levels by enzyme-linked immunosorbent assay at admission and functional outcomes of patients at 3 months after AIS.Results: Overall, 89 AIS patients (48 good outcomes and 41 poor outcomes) and 83 healthy controls were included. The median serum Homer1 level of patients at admission with poor outcomes was significantly higher than that of patients with good outcomes (39.33 vs 33.15, P< 0.001). Serum Homer1 levels at admission were positively correlated with the severity of AIS (r = 0.488, P< 0.001). The optimal cutoff of serum Homer1 level as an indicator for an auxiliary diagnosis of 3 months functional outcomes was 35.07 pg/mL, with a sensitivity of 75.0% and a specificity of 92.7% (AUC 0.837; 95% CI [0.744– 0.907]; P< 0 0.001). The odds ratio of MRS > 2 predicted by the level of serum Homer1 after 3 months was 1.665 (1.306– 2.122; P< 0.001).Conclusion: Serum concentrations of Homer1 have a high predictive value for neurobehavioral outcomes after acute ischemic stroke. Higher serum Homer1 levels (> 35.07 pg/mL) were positively associated with poor functional outcomes of patients 3 months post-stroke.Keywords: Homer1, acute ischemic stroke, biomarker, outcomes

Xudong Zhu,1,2 Jiahui Yu,3 Fulu Ai,1 Yue Wang,1 Wu Lv,1 Guilin Yu,1 Xiankui Cao,1 Jie Lin1 1Department of General Surgery, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, 110042, People’s Republic of China; 2Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of China; 3Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, People’s Republic of ChinaCorrespondence: Jie Lin; Xudong Zhu, Department of General Surgery, Cancer Hospital of China Medical University, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, 110042, People’s Republic of China, Tel +86 13940081800 ; +86 13354204706, Email linxiran0221@126.com; xdzhu@cmu.edu.cnPurpose: CD24 mediates a “don’t eat me” signal to escape the immune environment. However, the correlation between CD24 and PD-L1 is unclear. This study aimed to assess if CD24 can serve as a target for immunotherapy of triple-negative breast cancer (TNBC).Methods: Data on CD24 expression in breast cancer were acquired using the Oncomine and UALCAN tools. The role of CD24 expression on the prognosis of patients with TNBC was assessed using Kaplan–Meier analyses. Subsequently, STRING and TISIDB databases were used to construct protein–protein interaction networks and to explore immune-related molecules regulated by CD24. Immunofluorescence and immunohistochemistry assays were conducted to validate CD24 and PD-L1 expression and tumor infiltration lymphocyte (TIL) level. Survival analysis was also performed to explore the effect of CD24 and PD-L1 expression and TIL level in patients with TNBC. ShRNA was also used to explore the regulation role of CD24 on PD-L1 expression.Results: CD24 expression was significantly higher in breast cancer than in normal tissues, with high expression being significantly associated with a worse prognosis. CD24 was found to be significantly regulated by chemokines, immunoinhibitors, immunostimulators and TILs. Furthermore, CD24 expression showed a significant positive correlation with PD-L1 expression and a negative correlation with TIL level. In association with PD-L1, CD24 was found to positively regulate lymphocyte costimulation, T cell costimulation, and leukocyte activation. Furthermore, CD24 and PD-L1 co-expression contributed to worse survival outcomes. In addition, CD24 expression was found to attenuate the positive effects of high-level TILs on the prognosis of patients with TNBC. CD24 can also regulate the expression of PD-L1 in TNBC cells.Conclusion: CD24 may attenuate the positive effects of high TIL levels on survival and may facilitate the immune escape of TNBC by regulating PD-L1 expression. Thus, it is a potential target for immunotherapy in TNBC.Keywords: triple negative breast cancer, CD24, PD-L1, prognosis, immunotherapy

Radiomic features are being increasingly studied for clinical applications. We aimed to assess the agreement among radiomic features when computed by several groups by using different software packages under very tightly controlled conditions, which included standardized feature definitions and common image data sets. Ten sites (9 from the NCI's Quantitative Imaging Network] positron emission tomography-computed tomography working group plus one site from outside that group) participated in this project. Nine common quantitative imaging features were selected for comparison including features that describe morphology, intensity, shape, and texture. The common image data sets were: three 3D digital reference objects (DROs) and 10 patient image scans from the Lung Image Database Consortium data set using a specific lesion in each scan. Each object (DRO or lesion) was accompanied by an already-defined volume of interest, from which the features were calculated. Feature values for each object (DRO or lesion) were reported. The coefficient of variation (CV), expressed as a percentage, was calculated across software packages for each feature on each object. Thirteen sets of results were obtained for the DROs and patient data sets. Five of the 9 features showed excellent agreement with CV < 1%; 1 feature had moderate agreement (CV < 10%), and 3 features had larger variations (CV ≥ 10%) even after attempts at harmonization of feature calculations. This work highlights the value of feature definition standardization as well as the need to further clarify definitions for some features.

Beibei Xu,1 Dong Lu,1,2 Kaicai Liu,3 Weifu Lv,2 Jingkun Xiao,2 Xingming Zhang,2 Zhengfeng Zhang,2 Jie Chai,2 Lijun Wang2 1School of Graduate, Bengbu Medical College, Bengbu, 233030, People’s Republic of China; 2Department of Interventional Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, People’s Republic of China; 3Infection Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230000, People’s Republic of ChinaCorrespondence: Dong Lu, Department of Interventional Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No. 17, Lujiang Road, Hefei, Anhui, 230001, People’s Republic of China, Tel +86 18056000897, Email hyjh2004@126.comPurpose: Regorafenib is a standard second-line treatment for hepatocellular carcinoma (HCC). This study aimed to evaluate the efficacy and safety of regorafenib in the treatment of patients with Barcelona clinic liver cancer (BCLC) stage C HCC after failure of the first-line therapy and to analyze factors affecting the efficacy of regorafenib as the second-line treatment.Methods: A retrospective analysis was conducted on 103 BCLC stage C HCC patients who received regorafenib as the second-line treatment. Among them, 51 patients received regorafenib plus transarterial chemoembolization (TACE) and 52 patients received regorafenib alone. Progression-free survival (PFS), overall survival (OS), and adverse events were compared between the two groups, and factors influencing the efficacy of regorafenib were analyzed.Results: In patients with BCLC stage C HCC after failure of the first-line therapy, there was no statistically significant difference in median PFS between regorafenib plus TACE group and regorafenib group (5.3 vs 4.0 months, P=0.432). The median OS was significantly longer in the regorafenib plus TACE group than that in the regorafenib group (11.3 vs 8.2 months, P=0.034). Patients in both groups experienced adverse events at rates of 78.43% and 75%, respectively. Rates of grade III–IV serious adverse events were 19.61% and 13.46%, respectively. Hand-foot skin reactions, fatigue, abdominal pain, and hypertension were common side effects of regorafenib. The number of tumors was noted as an independent prognostic factor for PFS in the univariate and multivariate Cox regression analyses, while Eastern Cooperative Oncology Group (ECOG) performance status (ECOG-PS) score, tumor size, the number of tumors, and combined local therapy were independent prognostic factors for OS. Regorafenib combined with TACE treatment improved OS for patients with ECOG-PS scores of 0– 1, tumor size < 5 cm, and the number of tumors ≥ 3 compared with regorafenib alone.Conclusion: Regorafenib exhibited to be a safe and effective sequential therapy for patients with BCLC stage C HCC after failure of the first-line treatment, and its combination with TACE could achieve a higher efficacy. ECOG-PS score, tumor size, the number of tumors, and combined local therapy were noted as prognostic factors affecting patients with BCLC stage C HCC who were treated with regorafenib.Keywords: regorafenib, hepatocellular carcinoma, TACE, efficacy, prognostic factors

Wenbin Cai,1,2,&ast; Wei Lv,1,3,&ast; Li Meng,2 Yunyou Duan,1 Li Zhang1 1Department of Ultrasound Medical, Tangdu Hospital, the Fourth Military Medical University, Xi’an, People’s Republic of China; 2Department of Ultrasound Diagnostics, General Hospital of Tibet Military Region, Lhasa, People’s Republic of China; 3Department of Radiology, 305 Hospital of Chinese People’s Liberation Army, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Zhang, Department of Ultrasound Medical, Tangdu Hospital, 569&num; Xinsi Road, Baqiao District, Xi’an, People’s Republic of China, Tel +86-29-84777171, Fax +86-29-83510181, Email lilyzhang319_20@hotmail.comIntroduction: Nanobubble is an innovative ultrasound contrast agent that triggers the development of targeted imaging of HER2-positive breast cancer by combining with HER2 affibody and IR783. HPPH is a second-generation photosensitiser that is effective in treating tumours. Hence, the nanobubble-IR783-HPPH-affibody (NIHA) complex demonstrates considerable potential in the treatment of HER2-positive breast cancer.Methods: We fabricated the NIHA complex via an advanced thin-film hydration method and detected its characteristics such as particle size, morphology, stability, and cytotoxicity. Moreover, the effect of NIHA complex with laser on HER2-positive breast cancer was confirmed via in vitro and in vivo experiments.Results: The NIHA complex was spheroid, stable and exhibited no cytotoxicity; moreover, its particle size was 524.8 ± 53.3 nm (n = 5). In combination with laser treatment, NIHA complex reduced the cell viability and tumour volume, induced apoptosis of HER2-positive breast cancer cells, and prolonged survival of nude mice.Conclusion: The newly prepared NIHA complex with laser treatment has the potential on treating HER2-positive breast cancer.Keywords: HER2, breast cancer, HPPH, nanobubbles, laser

Huang Liu,1,* Zhixing Zhang,2,* Wei Lv,3 Qianyi Li,1 Zhaohui Qing,3 Xiaolin Zhong,4 Shaoqin Peng,3 Hai Lin,1 Houbin Zheng1 1Department of Andrology, NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Human Sperm Bank of Guangdong Province, Guangzhou, People’s Republic of China; 2Department of Ultrasonography, NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Human Sperm Bank of Guangdong Province, Guangzhou, People’s Republic of China; 3Department of Anesthesiology, NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Human Sperm Bank of Guangdong Province, Guangzhou, People’s Republic of China; 4Inpatient Department, NHC Key Laboratory of Male Reproduction and Genetics, Guangdong Provincial Reproductive Science Institute (Guangdong Provincial Fertility Hospital), Human Sperm Bank of Guangdong Province, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Houbin Zheng, Email zhenghoubin@126.comObjective: Microsurgery of andrology always brings unexpected findings. Scrotal calculi are rare and unique, which are easily confused with tumor. To understand its etiology and harm, our study retrospectively analyzed the clinical characteristics of men with scrotal calculi to provide a reference for clinical practice.Methods: The clinical data of patients who underwent microscopic testicular sperm extraction (MTESE) and microscopic epididymal sperm aspiration (MESA) from January 1, 2018 to December 31, 2021 were retrospectively analyzed. Data screening was performed on cases in which calculi were found or not, and the relationship between calculi and spermatogenesis was analyzed.Results: A total of 405 patients were recruited. After screening, 218 nonobstructive azoospermia (NOA), 83 obstructive azoospermia (OA), and 13 cryptozoospermia (CZ) patients were included in the study. Calculi were found in 3 patients [incidence was 0.74% (3/405)], in which 2 patients had obstructive azoospermia (1 was epididymal calculi, 1 was intrascrotal calculi) and 1 patient had cryptozoospermia (intrascrotal calculi). Pathological results showed that chronic granuloma with abscess infiltration appeared in epididymal tissue, basement membrane thickening and fibrosis appeared in seminiferous tubules, and fibrous hyperplasia with calcium deposition was found in scrotal calculus. White blood cells, lymphocytes, red blood cells, abstinence time and urethritis were closely related to the occurrence of calculi. While abstinence time might be a potential predictor, which increased the risk by approximately 1.2 times.Conclusion: Disturbance of the testicular microenvironment caused by lymphocyte infiltration may be the main reason for scrotal calculi and ultimately cause spermatogenesis disorders. Prolonged sexual abstinence was a potential risk.Keywords: intrascrotal calculi, azoospermia, cryptozoospermia, testicular microenvironment, lymphocyte infiltration, prolonged sexual abstinence, tumour

Yue Lin,1,&ast; Zheyan Chen,2,&ast; Yinai Liu,3 Jiawen Wang,2 Wang Lv,1 Renyi Peng3 1Department of Emergency, The Third Affiliated Hospital of Shanghai University & Wenzhou No. 3 Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People’s Hospital, Wenzhou, People’s Republic of China; 2Department of Plastic Surgery, The Third Affiliated Hospital of Shanghai University & Wenzhou No. 3 Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People’s Hospital, Wenzhou, People’s Republic of China; 3Institute of Life Sciences, College of Life and Environmental Science, Wenzhou University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Renyi Peng, Tel +86 159-5771-6937, Email 20170032@wzu.edu.cnAbstract: Skin injuries caused by accidents and acute or chronic diseases place a heavy burden on patients and health care systems. Current treatments mainly depend on preventing infection, debridement, and hemostasis and on supplementing growth factors, but patients will still have scar tissue proliferation or difficulty healing and other problems after treatment. Conventional treatment usually focuses on a single factor or process of wound repair and often ignores the influence of the wound pathological microenvironment on the final healing effect. Therefore, it is of substantial research value to develop multifunctional therapeutic methods that can actively regulate the wound microenvironment and reduce the oxidative stress level at the wound site to promote the repair of skin wounds. In recent years, various bioactive nanomaterials have shown great potential in tissue repair and regeneration due to their properties, including their unique surface interface effect, small size effect, enzyme activity and quantum effect. This review summarizes the mechanisms underlying skin wound repair and the defects in traditional treatment methods. We focus on analyzing the advantages of different types of nanomaterials and comment on their toxicity and side effects when used for skin wound repair.Keywords: nanomedicine, nanomaterials, nano-formulations, skin injury, wound repair

Wencong Lv,1 Jiaxin Luo,1 Qing Long,1 Jundi Yang,2 Xin Wang,1 Jia Guo1 1Clinical Nursing Department, Xiangya School of Nursing, Central South University, Changsha, Hunan, People’s Republic of China; 2Nursing Department, School of Nursing, The University of Hong Kong, Hong Kong, People’s Republic of ChinaCorrespondence: Jia GuoClinical Nursing Department, Xiangya School of Nursing, Central South University, 172 Tongzipo Road, Changsha, Hunan, 410013, People’s Republic of ChinaTel +86 13875947418Email guojia621@163.comBackground: Self-monitoring of blood glucose (SMBG) plays a crucial role in the maintenance of glycemic control in young people with type 1 diabetes mellitus (T1DM), but most of them do not perform SMBG as recommended. Few studies comprehensively explored factors that correlate with adherence to SMBG among this population on the basis of a framework. Hence, the aims of this study were to describe adherence to SMBG among young people with T1DM in China and explore its associating factors according to the Self and Family Management (SFM) framework.Methods: A cross-sectional study was conducted on young people with T1DM in Hunan Province of China from July to August 2020. Based on the SFM framework, self-reported questionnaires were organized for the collection of data on adherence to SMBG, socio-demographic and clinical factors, resources, health care system, and personal factors. Factors associated with adherence to SMBG were determined through multivariate logistic regression analysis.Results: A total of 165 young people were invited, of which 122 (73.9%) completed the questionnaires. The mean age was 12.41 years (SD = 3.18), and the proportion of young people who adhered to SMBG was 53.3%. Multivariate logistic regression analysis revealed that children aged 8– 12 years (OR = 0.188, P = 0.002), from two-parent families (OR = 0.232, P = 0.019), and with better personal factors (eg, with more information of SMBG, OR = 1.072, P = 0.020; lower diabetes-related worry, OR = 0.917, P = 0.031; higher level of pain during SMBG, OR = 1.852, P = 0.001), had better adherence to SMBG.Conclusion: Nearly half of the young people with T1DM were not adherent to SMBG in China. Clinicians need to pay more attention to adolescents from single-parent families with regard to their adherence to SMBG. Providing management strategies of SMBG, including delivering SMBG-related information, decreasing diabetes-related worry, and relieving pain related to SMBG, may improve adherence.Keywords: self-monitoring of blood glucose, young people, type 1 diabetes mellitus, influencing factors

Peipei Zhang,1,* Xiangde Min,1,* Zhaoyan Feng,1 Zhen Kang,1 Basen Li,1 Wei Cai,1 Chanyuan Fan,1 Xi Yin,1 Jinke Xie,1 Wenzhi Lv,2 Liang Wang1 1Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 2Department of Artificial Intelligence, Julei Technology Company, Wuhan 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang WangDepartment of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jie Fang Avenue, Qiaokou, Wuhan 430030, People’s Republic of ChinaTel +86-27-83663737Email wang6@tjh.tjmu.edu.cnPurpose: To compare the performance of histogram analysis and intra-perinodular textural transition (Ipris) for distinguishing between benign and malignant testicular lesions.Patients and Methods: This retrospective study included 76 patients with 80 pathologically confirmed testicular lesions (55 malignant, 25 benign). All patients underwent preoperative T2-weighted imaging (T2WI) on a 3.0T MR scanner. All testicular lesions were manually segmented on axial T2WI, and histogram and Ipris features were extracted. Thirty enrolled patients were randomly selected to estimate the robustness of the features. We used intraclass correlation coefficients (ICCs) to evaluate intra- and interobserver agreement of features, independent t-test or Mann–Whitney U-test to compare features between benign and malignant lesions, and receiver operating characteristic curve analysis to evaluate the diagnostic performance of features.Results: Eighteen histogram features and forty-eight Ipris features were extracted from T2WI of each lesion. Most (60/66) histogram and Ipris features had good robustness (ICC of both intra- and interobserver variabilities > 0.6). Three histogram and nine Ipris features were significantly different between the benign and malignant groups. The area under the curve values for Energy, TotalEnergy, and Ipris_shell1_id_std were 0.807, 0.808, and 0.708, respectively, which were relatively higher than those of other features.Conclusion: Ipris features may be useful for identifying benign and malignant testicular tumors but have no significant advantage over conventional histogram features.Keywords: magnetic resonance imaging, testicular disease, Ipris, texture analysis

Wenyi Lv,1 Jin Feng,1 Li Chen,1 Shuai Liu,1,2 Xiaoguang Qiu1,2 1Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, People’s Republic of China; 2Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, People’s Republic of ChinaCorrespondence: Xiaoguang Qiu; Shuai LiuBeijing Neurosurgical Institute, Capital Medical University, No. 119, South 4th Ring West Road, Fengtai District, Beijing 100070, People’s Republic of ChinaTel/Fax +86 1059975266; +86 1059975580Email qiuxiaoguang@bjtth.org; s.liu@bjtth.orgPurpose: Basal ganglia intracranial germ cell tumors (iGCTs) can specifically destroy the basal ganglia network, leading to several cognitive, learning, behavioral, and social impairments. This study aimed to investigate the behavior and social disorders of patients with basal ganglia iGCTs.Patients and Methods: We recruited 30 newly diagnosed iGCTs patients (and their parents) for the current study. The Child Behavior Checklist/6– 18 was used to evaluate emotional and behavioral problems. The Conner’s Parent Rating Scales was used to assess symptoms of hyperactivity/impulsivity and conduct problems. The health-related quality of life (HRQoL) was assessed using the Pediatric Quality of Life Inventory 4.0 Generic Core Scale. Performance status was assessed using the Lansky play-performance scale and Karnofsky performance scale. The effects of basal ganglia lesions on these scores were examined.Results: Patients with basal ganglia iGCTs (n = 10) had more behavioral problems (attention problems, aggressive behavior, learning problems, hyperactivity index), social function impairment, anxiety/depression, and poorer HRQoL compared to patients with non-basal ganglia iGCTs (n = 20). There was no significant difference in the Lansky play-performance/Karnofsky performance scale scores.Conclusion: This study demonstrates the effects of basal ganglia lesions on behavioral and emotional outcomes, social functions, and HRQoL of patients with iGCTs. The results may help to understand the function of basal ganglia and provide evidence for the benefit of early psychological intervention to improve the treatment for this rare disease.Keywords: intracranial germ cell tumors, pediatrics, The Child Behaviour Checklist, The Conner’s Parent Rating Scales, health-related quality of life

Xiufeng Zhang,1,2,* Fangping Li,3,* Shiyun Cui,1,2 Lisha Mao,4 Xiaohua Li,3 Furqan Awan,1,2 Weibiao Lv,5 Zhenling Zeng1,2 1College of Veterinary Medicine, Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, National Risk Assessment Laboratory for Antimicrobial Resistance of Microorganisms in Animals, South China Agricultural University, Guangzhou 510642, People’s Republic of China; 2Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Plant Molecular Breeding, State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou 510642, People’s Republic of China; 4Department of Clinical Laboratory, Cancer Hospital of Guangxi Medical University, Guangxi Medical University, Nanning 530021, People’s Republic of China; 5Department of Clinical Laboratory, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan 528000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weibiao Lv; Zhenling Zeng Email weibiao2004@163.com; zlzeng@scau.edu.cnBackground: Carbapenem-resistant Klebsiella pneumoniae infections have caused major concern and posed a global threat to public health. As blaKPC-2 and blaNDM-1 genes are the most widely reported carbapenem resistant genes in K. pneumonia, it is crucial to study the prevalence and geographical distribution of these two genes for further understanding of their transmission mode and mechanism.Purpose: Here, we investigated the prevalence and distribution of blaKPC-2 and blaNDM-1 genes in carbapenem-resistant K. pneumoniae strains from a tertiary hospital and from 1579 genomes available in the NCBI database, and further analyzed the possible core structure of blaKPC-2 or blaNDM-1 genes among global genome data.Materials and Methods: K. pneumoniae strains from a tertiary hospital in China during 2013– 2018 were collected and their antimicrobial susceptibility testing for 28 antibiotics was determined. Whole-genome sequencing of carbapenem-resistant K. pneumoniae strains was used to investigate the genetic characterization. The phylogenetic relationships of these strains were investigated through pan-genome analysis. The epidemiology and distribution of blaKPC-2 and blaNDM-1 genes in K. pneumoniae based on 1579 global genomes and carbapenem-resistant K. pneumoniae strains from hospital were analyzed using bioinformatics. The possible core structure carrying blaKPC-2 or blaNDM-1 genes was investigated among global data.Results: A total of 19 carbapenem-resistant K. pneumoniae were isolated in a tertiary hospital. All isolates had a multi-resistant pattern and eight kinds of resistance genes. The phylogenetic analysis showed all isolates in the hospital were dominated by two lineages composed of ST11 and ST25, respectively. ST11 and ST25 were the major ST type carrying blaKPC-2 and blaNDM-1 genes, respectively. Among 1579 global genomes data, 147 known ST types (1195 genomes) have been identified, while ST258 (23.6%) and ST11 (22.1%) were the globally prevalent clones among the known ST types. Genetic environment analysis showed that the ISKpn7-dnaA/ISKpn27 -blaKPC-2-ISkpn6 and blaNDM-1-ble-trpf-nagA may be the core structure in the horizontal transfer of blaKPC-2 and blaNDM-1, respectively. In addition, DNA transferase (hin) may be involved in the horizontal transfer or the expression of blaNDM-1.Conclusion: There was clonal transmission of carbapenem-resistant K. pneumoniae in the tertiary hospital in China. The prevalence and distribution of blaKPC-2 and blaNDM-1 varied by countries and were driven by different transposons carrying the core structure. This study shed light on the genetic environment of blaKPC-2 and blaNDM-1 and offered basic information about the mechanism of carbapenem-resistant K. pneumoniae dissemination.Keywords: Klebsiella pneumoniae, blaKPC-2, *blaNDM-1, bioinformatics

Shuwei Wang, Xinru Guo, Wenying Lv, Yanteng Li, Leiming Zhang, Chao Dong, Jianning Zhang, Gang Cheng Department of Neurosurgery, Sixth Medical Center, Chinese PLA General Hospital, Beijing 100048, People’s Republic of ChinaCorrespondence: Jianning Zhang; Gang ChengDepartment of Neurosurgery, Sixth Medical Center, Chinese PLA General Hospital, No. 6 Pucheng Road, Beijing 100048, People’s Republic of ChinaTel +86 10-66951351Email jianningz36@aliyun.com; bgsvsaswgxo6@163.comIntroduction: Ribosomal protein SA pseudogene 52 (RPSAP52) has been characterized as an oncogenic lncRNA in pituitary tumors. Analysis of TCGA dataset revealed the upregulation of RPSAP52 in glioblastoma (GBM). We, therefore, investigated the roles of RPSAP52 in GBM.Methods: A total of 50 GBM patients (33 males and 20 females; 54– 75 years; mean age: 61.8± 5.8 years) were selected from the 89 cases of GBM patients. Under the guidance of MRI, brain biopsy was performed to collect GBM tissues from each patient for the diagnosis of GBM. U-373 MG cells were employed and had transient transfections. qRNA, Western blot, and a series of experiments were performed to characterize their associations.Results: The results showed that RPSAP52 was upregulated in GBM patients, and its high expression levels predicted poor survival. In GBM tissues, expression levels of RPSAP52 were significantly and positively correlated with that of TGF-β 1. In GBM tissues, RPSAP52 positively regulated the expression of TGF-β 1. Cell stemness assay showed that, compared to C and NC groups, overexpression of RPSAP52 and TGF-β 1 led to increased, while silencing of RPSAP52 led to decreased CD133+ cells. Overexpression of TGF-β 1 attenuated the effects of RPSAP52 siRNA silencing.Conclusion: Therefore, RPSAP52 upregulates TGF-β 1 to increase cancer cell stemness and predict postoperative survival in GBM.Keywords: glioblastoma, RPSAP52, TGF-β 1, survival, stemness

Xiufeng Zhang,1–3 Dongdong Han,1–3 Pengfei Pei,1–3 Jie Hao,1–3 Yixing Lu,1–3 Peng Wan,1–3 Xianfeng Peng,4 Weibiao Lv,5 Wenguang Xiong,1–3 Zhenling Zeng1–3 1National Laboratory of Safety Evaluation (Environmental Assessment) of Veterinary Drugs, South China Agricultural University, Guangzhou 510642, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Veterinary Drugs Development and Safety Evaluation, South China Agricultural University, Guangzhou 510642, People’s Republic of China; 3National Risk Assessment Laboratory for Antimicrobial Resistance of Animal Original Bacteria, South China Agricultural University, Guangzhou 510642, People’s Republic of China; 4Guangzhou Insighter Biotechnology Co., Ltd, Guangzhou 510642, People’s Republic of China; 5Department of Clinical Laboratory, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan 528000, People’s Republic of ChinaCorrespondence: Wenguang Xiong; Zhenling ZengSouth China Agricultural University, Wushan Road, Tianhe District, Guangzhou 510642, People’s Republic of ChinaTel +86 20-85281204Fax +86 20-85284896Email xiongwg@scau.edu.cn; zlzeng@scau.edu.cnBackground: Bacterial infections cause a serious public health crisis due to the emergence of resistance towards multiple conventional antibacterial drugs. In particular, multidrug-resistant (MDR) Enterococcus faecium which belongs to “ESKAPE” organisms is causing significant problems worldwide. Hence, there is an urgent need to find alternative therapies. Recently, substituted benzene guanidine compounds have been used as lead structures to discover new promising drugs in both synthetic and medicinal chemistry.Purpose: Here we investigated the antimicrobial activity of a new substituted benzene guanidine analog, isopropoxy benzene guanidine, against Enterococci.Material and methods: The isopropoxy benzene guanidine was synthesized by Guangzhou Insighter Biotechnology Co., Ltd and tested on both reference bacterial strain and 32 clinical MDR Enterococci strains. The in vitro antibacterial activity was evaluated by microdilution method and kill kinetic assays. The potential antibacterial mechanism was measured by fluorescence spectrometry using fluorescent membrane potential probe 3, 3-diethyloxacarbocyanine iodide (DiOC2 (3)).Results: Isopropoxy benzene guanidine exhibited potent bactericidal activity against both reference strain and MDR Enterococci isolates. The minimum inhibitory concentration (MIC) range for isopropoxy benzene guanidine was 1–4 μg/mL. Minimum bactericidal concentration (MBC) was about 2-8-fold of its MIC values. Time-kill studies showed that isopropoxy benzene guanidine provided superior bactericidal effect against reference and MDR strains within 12 hrs at 2×MIC. Furthermore, isopropoxy benzene guanidine could cause a large reduction in the magnitude of the generated membrane potential compared to that of the untreated cells.Conclusion: The present study highlights the potent bactericidal activity of isopropoxy benzene guanidine on Enterococci by disrupting the cell membrane potential. These findings demonstrate that isopropoxy benzene guanidine may be a good chemical lead for further medicinal chemistry and pharmaceutical development and could be used as a therapeutic agent for infectious diseases caused by MDR Enterococci.Keywords: isopropoxy benzene guanidine, MDR Enterococci, DiOC2, 3, cell membrane potential, bactericidal activity

Hengli Yang,1,2,* Wenbin Cai,3,* Wei Lv,2 Ping Zhao,2 Yamei Shen,4 Longfang Zhang,1 Bin Ma,1 Lijun Yuan,2 Yunyou Duan,2 Kechun Yao11Department of Ultrasound Diagnosis, Air Force General Hospital, Beijing, People’s Republic of China; 2Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China; 3Special Diagnosis Department, General Hospital of Tibet Military Command, Lhasa, People’s Republic of China; 4Department of Ultrasound Diagnosis, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China *These authors contributed equally to this workCorrespondence: Yunyou DuanDepartment of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi’an 710038, People’s Republic of ChinaEmail duanyy@fmmu.edu.cnKechun YaoDepartment of Ultrasound Diagnosis, Air Force General Hospital, Beijing 100036, People’s Republic of ChinaEmail yaokc1959@hotmail.comBackground: Currently, effective detection and treatment of cutaneous malignant melanoma (CMM) still face severe challenges. Ultrasound molecular imaging as a noninvasive and easy-to-operate method is expected to bring improvements for tumor detection.Purpose: The aim of this research is to prepare novel phase-change ultrasound contrast agents, Nds-IR780, which can perform not only dual-mode molecule-targeted imaging but also targeted photothermal therapy for CMM.Methods: A double emulsion process was used to prepare the Nds-IR780. Then, the entrapment rate and drug loading of IR-780 iodide in Nds-IR780 were detected by high-performance liquid chromatography. The biocompatibility of Nds-IR780 was evaluated by a CCK-8 assay and the characteristics and stability of that were verified through the particle size analyzer, laser scanning confocal microscopy (LSCM) and transmission electron microscopy (TEM). The abilities of dual-mode molecule-targeted imaging and targeted photothermal therapy for Nds-IR780 were confirmed via the in vitro and in vivo experiments.Results: Nds-IR780 had good size distribution, polydispersity index, stability and biosafety. The in vitro and in vivo experiments confirmed that Nds-IR780 were capable of targeting CMM cells with high affinity (22.4±3.2%) and facilitating dual-mode imaging to detect the primary lesion and sentinel lymph nodes (SLNs) of CMM. Furthermore, the photothermal ablation of CMM mediated by Nds-IR780 was very effective in vivo.Conclusion: The newly prepared Nds-IR780 were observed to be effective targeted theranostic probe for the precise detection and targeted treatment of CMM.Keywords: CMM, dual-mode phase-change nanodroplets, targeted accurate diagnosis and treatment

Hui-xia Yang, Yu Zhong, Wei-hua Lv, Hong YuLabor Model Health Management Center, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Hong YuLabor Model Health Management Center, Beijing Rehabilitation Hospital, Capital Medical University, Xixiazhuang, Badachu, Shijingshan District, Beijing 100144, People’s Republic of ChinaTel +86 105 698 1131Fax +86 105 698 1131Email y_hong@aliyun.comBackground: In 2018, the Beijing Federation of Trade Unions organized a cervical cancer screening program for female employees for the first time. This study aimed to investigate the screening results of this program and determine the factors associated with human papillomavirus (HPV) infection.Methods: A total of 8297 female employees participating in the screening program between January 1, 2018, and December 31, 2018, were enrolled in this study. The methods for screening cervical cancer included ThinPrep cytology test (TCT) and HPV genotyping test. Single-factor analysis and multiple binary logistic regression analysis were used to identify the factors associated with HPV infection.Results: Of the 8297 women (median age: 43.00 years), TCT was found to be abnormal in 116 patients (1.40%) and 1169 (14.09%) were positive for HPV genotyping test. Notably, HPV-52 was the most prevalent subtype (3.05%), followed by HPV-16 (2.82%), HPV-58 (2.01%), HPV-51 (1.58%) and HPV-56 (1.49%). Multivariate logistic regression analysis revealed that taxi drivers (OR =1.98; 95% CI =1.31–2.99) and single women with a history of sexual activity (OR =2.32; 95% CI =1.41–3.82) were significantly associated with an increased risk of HPV infection (P

Wenbin Cai,1,2,* Wei Lv,1,3,* Yang Feng,4 Hengli Yang,1 Yajun Zhang,1 Guodong Yang,5 Yunyou Duan,1 Jia Wang1 1Department of Ultrasound Diagnosis, Tang Du Hospital, Fourth Military Medical University, Xi’an 710038, China; 2General Hospital of Tibet Military Command, Lhasa, Tibet Autonomous Region, 850007, China; 3Department of Radiology, 305 Hospital of Chinese People’s Liberation Army, Xicheng District, Beijing, 100017, China; 4Xijing Hospital, Traditional Chinese Medicine, Xi’an 710032, China; 5Department of Biochemistry and Molecular Biology, The Fourth Military Medical University, Xi’an 710032, China *These authors contributed equally to this work Background: Nanobubbles (NBs) combined with ultrasound-targeted destruction (UTD) have become promising potential carriers for drug or siRNA delivery. Due to their nano-size, NBs could penetrate tumor blood vessels and accumulate in intercellular spaces so that “sonoporation” induced by UTD would act directly on the tumor cells to increase cell membrane permeability. Methods: Based on the successful the fabrication of NBs, we synthesized NBs carrying siRNA (NBs-siRNA) by using a biotin-streptavidin system. We then utilized ultrasound irradiation (UI)-targeted NBs-siRNA to improve siRNA transfection and achieve the inhibition of glioma growth.Results: NBs as carriers combined with UI effectively enhanced siRNA transfection and the effect of silencing targeted genes in vitro. Additionally, a better therapeutic effect was shown in the NBs-siRNA with UI group in vivo compared with that of microbubbles (MBs) with UI or NBs-siRNA without UI.Conclusion: These results indicated that NBs combined with UTD might be an ideal delivery vector for siRNA to achieve the noninvasive treatment of glioma. Keywords: nanobubbles, ultrasound, siRNA, glioma

Jin Ma,1,* Chunxia Yin,1,* Shiyu Ma,2 Huiliang Qiu,1 Chaoyang Zheng,1 Qiuxiong Chen,1 Chunhua Ding,1,3 Weihui Lv1 1Heart Center, Guangdong Provincial Hospital of Chinese Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; 2Department of Critical-Care Medicine, Guangdong Provincial Hospital of Chinese Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; 3Cardiac Department, Aerospace Center Hospital, Peking University Aerospace Clinical College of Medicine, Beijing 100049, China *These authors contributed equally to this work Purpose: Shensong Yangxin (SSYX) capsule is a traditional Chinese medicine that has been used widely to treat cardiac arrhythmia. This study aimed to assess whether SSYX prevents atrial fibrillation (AF) after chronic myocardial infarction (MI)-induced heart failure and to determine the underlying mechanisms.Materials and methods: The study included 45 male Sprague Dawley rats. The rats underwent MI induction or sham surgery. One week after MI induction surgery, we performed serial echocardiography and administered SSYX capsule to some rats that experienced MI. After 4 weeks of treatment, AF inducibility was assessed with transesophageal programmed electrical stimulation technology. Additionally, multielectrode array assessment, histological analysis, and Western blot analysis were performed.Results: AF inducibility was significantly lower in SSYX rats than in MI rats (33.3% vs 73.3%, P

Lijuan Zhou,1,* Yanqiu Gao,2 Wei Cao,1 Jia Liu,1 Hongya Guan,1 Hua Zhang,2 Yun Shi,3 Wenying Lv,4 Long Cheng5,* 1Translational Medicine Center, 2Department of Respiratory Medicine, Affiliated Zhengzhou Central Hospital of Zhengzhou University, Zhengzhou, 3Department of Gynecology, Dongzhimen Hospital, Beijing University of Chinese Medicine, 4Chaoyangmen Community Health Service Center, 5Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China *These authors contributed equally to this work Objectives: Teicoplanin, an antibiotic, has poor clinical efficacy when using the current drug label’s recommended regimen, which is approved by the China Food and Drug Administration. This study explores the appropriate loading and maintenance doses of teicoplanin and evaluates the therapeutic target of teicoplanin trough concentration (minimum concentration [Cmin]).Subjects and methods: All patients treated with teicoplanin from February 2015 to August 2016 at Zhengzhou Central Hospital were screened for enrollment. A total of 113 subjects were included and then divided into four groups: A (received three to six doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 400 mg/day), B (received three doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 400 mg/day), C (received two doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 200 mg/day), and D (received one to three doses at a loading dose of 400 mg at 12-hour intervals, followed by maintenance dosing of 200 mg/day). Cmin values of teicoplanin were detected with high-performance liquid chromatography on day 4, 30 minutes before maintenance-dose administration. Teicoplanin Cmin, efficacy, and safety were compared among the four groups.Results: Mean Cmin differed significantly among the four groups (A, 18.11±6.37 mg/L; B, 15.91±4.94 mg/L; C, 17.06±5.66 mg/L; D, 11.97±3.76 mg/L) (P